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ACTA2

The ACTA2 gene encodes a protein known as smooth muscle alpha (α)-2 actin, a member of the actin protein family that is highly conserved across species and essential for cellular structure and motility.^[1] This protein is predominantly expressed in smooth muscle cells, where it forms thin filaments that interact with myosin to enable contraction, playing a critical role in the involuntary movements of organs such as blood vessels, the digestive tract, and the bladder.^[1] In vascular smooth muscle, ACTA2-derived actin helps maintain arterial wall integrity by allowing controlled contraction and relaxation in response to blood pressure changes.^[2] Mutations in the ACTA2 gene disrupt the structure and function of alpha-2 actin, leading to impaired smooth muscle contraction and a range of hereditary disorders primarily affecting the cardiovascular and cerebrovascular systems.^[3] Over 30 distinct mutations have been identified in individuals with familial thoracic aortic aneurysm and dissection (FTAAD), the most common associated condition, where these variants often alter key amino acids, weakening the aortic wall and increasing the risk of life-threatening rupture or dissection.^[1] Specific mutations, such as the Arg179His variant, cause multisystemic smooth muscle dysfunction syndrome, characterized by widespread abnormalities including vascular malformations, mydriasis (dilated pupils), bladder and gastrointestinal hypomotility, and hypoperistalsis.^[1] Beyond aortic disease, ACTA2 mutations are linked to early-onset coronary artery disease, ischemic stroke, and Moyamoya disease, reflecting the gene's broad impact on vascular smooth muscle throughout the body.^[3] These variants account for approximately 10-15% of non-syndromic thoracic aortic aneurysms and are associated with a high lifetime risk of aortic events, often presenting acutely with dissection in affected families.^[4] Pathogenic changes in ACTA2 can also contribute to congenital heart defects like bicuspid aortic valve and iris flocculi, underscoring its role in multisystem developmental processes.^[5] As of 2025, preclinical research has advanced CRISPR-based gene editing therapies targeting ACTA2 mutations, such as Arg179His, showing promise for treating multisystemic smooth muscle dysfunction syndrome.^[6]^[7]

Gene

Genomic Location

The ACTA2 gene is situated on the long arm of human chromosome 10 in the cytogenetic band 10q23.31.^[2] In the GRCh38.p14 reference assembly, it occupies the genomic coordinates 10:88,934,822-88,991,339 on the reverse strand.^[8] This positioning places ACTA2 within a region associated with vascular and smooth muscle-related functions, though specific regulatory elements in the locus require further characterization. The gene spans approximately 56 kb and comprises 9 exons in its canonical transcript.^[8]^[9] The surrounding genomic context includes the antisense RNA gene ACTA2-AS1 immediately upstream, contributing to a compact locus with potential cis-regulatory interactions.^[10] ACTA2 exhibits strong evolutionary conservation, with orthologs identified in numerous species, including the mouse Acta2 gene on chromosome 19 (coordinates 34,217,736-34,232,985 in GRCm39).^[11] Across mammals, the gene has at least 138 orthologues, reflecting its fundamental role in actin-mediated processes and minimal tolerance for sequence divergence.^[8]

Structure and Expression

The ACTA2 gene spans approximately 56 kb and consists of 9 exons separated by 8 introns, with the coding sequence distributed across exons 2 through 8, while exons 1 and 9 contain the 5' and 3' untranslated regions (UTRs), respectively.^[8] This architecture results in a primary transcript that is processed into a mature mRNA of about 1.3 kb, encoding the 377-amino-acid α-smooth muscle actin protein.^[9] The exon-intron boundaries are conserved, reflecting the evolutionary stability of actin genes, and the UTRs play roles in mRNA stability and translational efficiency.^[3] The promoter region of ACTA2 is rich in cis-regulatory elements, notably multiple CArG boxes (CC(A/T)₆GG motifs) that serve as binding sites for the transcription factor serum response factor (SRF).^[12] SRF interacts with these elements to drive tissue-specific expression, and its activity is enhanced by the coactivator myocardin, which forms a ternary complex with SRF on the promoter to activate transcription in smooth muscle lineages.^[13] This regulatory mechanism ensures precise control, with myocardin expression correlating closely with ACTA2 induction during cellular differentiation.^[14] ACTA2 exhibits a highly specific expression profile, with elevated levels in vascular smooth muscle cells of the aorta and arteries, as well as in the smooth muscle of the esophagus and urinary bladder.^[15] Expression is lower in non-vascular smooth muscles, such as those in the gastrointestinal tract outside the esophagus, and the gene is also detected at moderate levels in other contractile tissues like the seminal vesicles and endometrium.^[15] Beyond smooth muscle, ACTA2 is upregulated in fibroblasts transitioning to myofibroblasts, where it serves as a hallmark of differentiation in response to transforming growth factor-β1 (TGF-β1) signaling.^[16] During embryogenesis, ACTA2 expression is upregulated in developing vascular tissues, marking the differentiation of smooth muscle cells and pericytes around endothelial tubes as early as 3 days post-fertilization in model organisms.^[17] This temporal pattern aligns with the formation of vascular networks, where ACTA2 contributes to mural cell maturation and vessel stabilization.^[18]

Protein

Primary Structure

The ACTA2 gene encodes the protein actin, alpha-2, smooth muscle, also known as α-smooth muscle actin (α-SMA), with the UniProt identifier P62736.^[19] This protein consists of 377 amino acids and has a calculated molecular weight of 42,009 Da.^[10] The primary amino acid sequence of α-SMA is highly conserved among actin family members, featuring a characteristic structure that includes four major domains typical of all actin proteins, which facilitate polymerization into filaments.^[19] A key post-translational modification in the primary structure of α-SMA is N-terminal acetylation, resulting in the mature sequence beginning with Ac-EEED (acetylated glutamic acid followed by three additional acidic residues).^[20] This acetylation occurs after the initial N-terminal methionine is cleaved, a process mediated by specific methionine aminopeptidases and acetyltransferases such as NAA80, which is essential for the protein's stability and function.^[21] Additionally, the sequence contains conserved actin domains, notably the nucleotide-binding site in subdomains I and III, where residues such as glycine-12, lysine-18, and aspartate-154 coordinate ATP binding, enabling the protein's role in energy-dependent conformational changes.^[19] In humans, ACTA2 primarily produces one major isoform corresponding to the canonical 377-amino-acid sequence, with minor variants arising from alternative splicing being rare and generally non-functional or truncated.^[19] Compared to other actin isoforms, α-SMA shares approximately 93% sequence identity with skeletal muscle alpha-actin (encoded by ACTA1), but it is distinguished by smooth muscle-specific residues, particularly in the N-terminal region (Ac-EEED versus Ac-DAD in ACTA1) and a few positions in the middle domain that influence filament assembly and tissue-specific interactions.^[22] These differences, though subtle, contribute to the isoform's specialized localization in vascular and visceral smooth muscle.^[20]

Function in Cellular Processes

The ACTA2 protein, known as α-smooth muscle actin (α-SMA), plays a central role in cellular cytoskeletal dynamics by polymerizing into filamentous actin (F-actin) structures that provide mechanical support and enable various motility processes. Monomeric globular actin (G-actin) bound to ATP adds to the growing filament, followed by ATP hydrolysis, which destabilizes the filament and promotes treadmilling for dynamic remodeling. This process follows the reaction:

\text{G-actin-ATP} \rightarrow \text{F-actin-ADP + P}_\text{i}

In smooth muscle cells, α-SMA polymerization is particularly efficient due to its specific N-terminal sequence, facilitating rapid incorporation into stress fibers under mechanical tension.^[23] α-SMA interacts with key regulatory proteins to modulate cytoskeletal architecture and function. It binds myosin II to generate contractile forces within stress fibers, enhancing cellular tension, and associates with tropomyosin isoforms such as Tpm1.6 and Tpm2.1, which stabilize F-actin filaments and inhibit depolymerization by preventing cofilin binding. These interactions are crucial for forming robust stress fibers and focal adhesions, where α-SMA links the cytoskeleton to the extracellular matrix via integrins, promoting adhesion maturation and force transmission. Cofilin, in turn, severs ADP-bound α-SMA filaments to regulate turnover, allowing adaptive remodeling in response to signals.^[24]^[23]^[25] In cellular motility, α-SMA is essential for directed migration in smooth muscle cells and fibroblasts by supporting lamellipodia extension and rear retraction through stress fiber contractility. Its expression enables efficient cell movement during wound healing and tissue remodeling, with knockdown impairing migration velocity. Additionally, α-SMA contributes to cytokinesis by incorporating into the contractile ring, aiding midbody formation and daughter cell separation via myosin-mediated constriction.^[26]^[27]^[28] α-SMA participates in RhoA/ROCK signaling pathways to drive cytoskeletal remodeling, where RhoA activation inhibits cofilin and promotes myosin light chain phosphorylation, enhancing α-SMA filament assembly and stress fiber bundling. This pathway is vital for mechanosensitive responses, such as focal adhesion growth under tension, ensuring cellular adaptation to environmental cues.^[25]^[29]

Role in Physiology

Smooth Muscle Contraction

α-Smooth muscle actin (α-SMA), encoded by the ACTA2 gene, forms the primary component of thin filaments in the contractile apparatus of vascular and visceral smooth muscle cells, where it interacts with myosin II to generate contractile force. This interaction follows the sliding filament model, in which myosin II heads cyclically bind to α-SMA filaments, hydrolyze ATP, and pull the filaments toward the center of the sarcomere-like structure, resulting in muscle shortening and force production essential for tissue contraction. In smooth muscle, unlike striated muscle, these filaments are not organized into regular sarcomeres but form a dense network that allows for sustained tonic contractions.^[30]^[2]^[31] Calcium ions (Ca²⁺) play a central role in regulating α-SMA-mediated contraction through interactions with actin-binding proteins such as caldesmon and calponin. At resting Ca²⁺ levels, caldesmon and calponin bind to α-SMA filaments, inhibiting the actin-activated Mg²⁺-ATPase activity of myosin II and preventing cross-bridge formation. Upon stimulation, increased intracellular Ca²⁺ binds to calmodulin, leading to phosphorylation of these proteins or their displacement from actin, thereby relieving inhibition and enabling myosin II to interact with α-SMA for contraction. This Ca²⁺-dependent thin filament regulation complements the thick filament mechanism involving myosin light chain phosphorylation, ensuring precise control of smooth muscle tone.^[32]^[33]^[34] In vascular physiology, α-SMA is crucial for maintaining arterial tone and regulating blood pressure via constriction of aortic and arterial smooth muscle layers. Deficiency in ACTA2 expression, as observed in knockout models, results in hypotension and impaired aortic contractility in response to agonists, highlighting its indispensable role in sustaining vascular resistance and hemodynamic stability. Disruptions in α-SMA function compromise the ability of smooth muscle to respond to vasopressive signals, potentially leading to altered blood flow dynamics.^[35]^[6] ACTA2 expression is dynamically regulated in response to hypertensive stimuli. Angiotensin II can lead to sustained downregulation of α-SMA in vascular smooth muscle cells, contributing to a phenotypic switch toward a synthetic state and vascular remodeling, as seen in models of transient hypertension. In contrast, angiotensin II directly stimulates α-SMA expression in cardiomyocytes and associated fibroblastic cells, while endothelin-1 induces α-SMA expression in smooth muscle-like mesangial cells, supporting adaptive responses in non-vascular contexts.^[36]^[37]^[38]

Expression in Non-Muscle Cells

In non-muscle cells, ACTA2 expression is primarily inducible and serves as a hallmark of cellular differentiation into contractile phenotypes, particularly in response to pathological stimuli. In fibroblasts, ACTA2 encodes α-smooth muscle actin (α-SMA), which emerges as a key marker of myofibroblast differentiation triggered by transforming growth factor-β (TGF-β) signaling. This pathway activates Smad-dependent transcription factors that bind to the ACTA2 promoter, upregulating α-SMA expression and enabling fibroblasts to acquire contractile properties essential for tissue remodeling.^[39]^[40] Studies in various fibroblast models, including cardiac and periodontal ligament cells, confirm that TGF-β1 directly induces ACTA2 transcription, enhancing cellular contractility without altering baseline actin isoforms.^[27] During wound healing, ACTA2 is temporarily upregulated in resident fibroblasts, promoting their transition to myofibroblasts that facilitate wound contraction and extracellular matrix (ECM) deposition for scar formation. This expression peaks in the proliferative and remodeling phases, where α-SMA-positive myofibroblasts generate tensile forces to close the wound and synthesize collagen-rich ECM, contributing to scar architecture.^[16] In human skin wounds, ACTA2 mRNA and protein levels are significantly elevated in scar tissue compared to unwounded dermis, underscoring its role in fibrosis resolution, though excessive persistence can lead to hypertrophic scarring.^[41] In the tumor microenvironment, ACTA2 is expressed in cancer-associated fibroblasts (CAFs), where it defines a myofibroblastic subtype that supports tumor progression and invasion. These α-SMA-positive CAFs remodel the stromal ECM through secretion of matrix metalloproteinases and fibrillar collagens, creating tracks that enhance cancer cell motility and metastasis.^[42] High ACTA2 expression in CAFs correlates with aggressive tumor behavior across various cancers, including breast and lung adenocarcinomas, by promoting a desmoplastic stroma that shields tumors from immune surveillance and chemotherapy.^[43] Beyond fibroblasts, ACTA2 is detected in pericytes and endothelial cells under stress conditions, reflecting adaptive responses to vascular injury. In pericytes, which envelop microvessels, constitutive low-level ACTA2 expression increases during hypoxia or inflammation, stabilizing vessel integrity and modulating blood flow.^[16] Under pathological stress, such as shear alterations or tumor angiogenesis, endothelial cells undergo endothelial-to-mesenchymal transition (EndMT), acquiring mesenchymal features including ACTA2 upregulation, which contributes to stromal fibrosis and vascular remodeling.^[44]^[45] This inducible expression highlights ACTA2's versatility in non-muscle contexts, distinct from its constitutive role in smooth muscle contraction.

Clinical Significance

Associated Diseases

Mutations in the ACTA2 gene, which encodes smooth muscle alpha-actin, are linked to a spectrum of disorders primarily affecting vascular and smooth muscle tissues due to impaired contractile function in smooth muscle cells.^[46] These conditions often manifest with early-onset vascular anomalies and multisystem involvement, highlighting ACTA2's critical role in maintaining vascular integrity and smooth muscle homeostasis.^[2] Familial thoracic aortic aneurysm and dissection (TAAD) represents one of the primary disorders associated with ACTA2 dysfunction, accounting for 12-21% of non-syndromic familial cases.^[46] Individuals with ACTA2-related TAAD typically experience early aortic dilation, often presenting in childhood or young adulthood, with a high lifetime risk of aortic dissection or rupture, estimated at up to 76% by age 85.^[47] This condition underscores the gene's importance in aortic wall stability, where defective actin polymerization leads to progressive weakening of the vessel.^[4] Multisystemic smooth muscle dysfunction syndrome (MSMDS), also known as smooth muscle dysfunction syndrome, arises from specific ACTA2 variants and affects multiple organ systems reliant on smooth muscle, including the lungs, bladder, gastrointestinal tract, and eyes.^[48] Patients often exhibit congenital mydriasis, hypotonia, myopathy, and respiratory issues such as hypoplastic lungs, alongside gastrointestinal and urinary tract malformations that can lead to chronic dysfunction.^[49] This syndrome is particularly severe in infancy, with features like persistent ductus arteriosus contributing to early morbidity.^[50] ACTA2 mutations are also implicated in Moyamoya disease, a progressive cerebrovascular disorder characterized by stenosis and occlusion of intracranial arteries due to abnormal smooth muscle cell proliferation.^[51] This leads to the formation of fragile collateral vessels, increasing stroke risk, and presents a distinctive phenotype compared to idiopathic Moyamoya, often with earlier onset and associated aortic involvement.^[52] Additional associations include early-onset coronary artery disease, where ACTA2 variants promote atherosclerosis and myocardial infarction in young adults despite normal cholesterol levels, driven by disrupted vascular smooth muscle cell function.^[53] Persistent ductus arteriosus frequently co-occurs, particularly in multisystemic cases, failing to close postnatally and necessitating intervention.^[54] Furthermore, upregulated ACTA2 expression in hepatic stellate cells contributes to liver fibrosis progression, linking the gene to extracellular matrix deposition in chronic liver injury models.^[55]

Pathogenic Mutations

Pathogenic mutations in the ACTA2 gene are predominantly heterozygous missense variants that alter the amino acid sequence of the α-smooth muscle actin protein, leading to dysfunctional smooth muscle cells (SMCs). These mutations account for approximately 12-21% of familial thoracic aortic aneurysm and dissection (TAAD) cases, with over 40 distinct variants identified to date. For instance, the R179H and R179C variants are particularly associated with multisystemic smooth muscle dysfunction syndrome (MSMDS), while variants such as R149C and R258C are recurrent in TAAD.^[56]^[57] Mutation hotspots are concentrated in evolutionarily conserved regions of the actin protein, particularly the actin filament-binding domains and subdomains involved in polymerization and protein interactions, such as subdomains 1, 3, and 4. The R149C mutation, located in subdomain 3 near the nucleotide-binding cleft, exemplifies this by impairing actin filament formation and stability. Similarly, the R258C variant in subdomain 4 disrupts the hydrophobic core, affecting filament dynamics. These locations underscore the critical role of structural integrity in actin function.^[56]^[58]^[59] ACTA2 mutations follow an autosomal dominant inheritance pattern with incomplete and age-dependent penetrance, with a cumulative risk of aortic events estimated at 76% by age 85. This variability arises from factors like genetic background and environmental influences, resulting in diverse clinical outcomes even within families.^[4] At the molecular level, these mutations exert dominant-negative or loss-of-function effects by disrupting actin-myosin interactions and filament polymerization, which weakens vascular SMC contractility and compromises vessel wall integrity. For example, the R149C mutation reduces integrin recruitment and alters SMC phenotype toward a more proliferative state, contributing to aortic dilation and dissection risk. In MSMDS, the R179 variants further impair SMC differentiation, leading to widespread dysfunction beyond the aorta. Overall, these changes promote SMC apoptosis or phenotypic switching, exacerbating vascular fragility.^[56]^[58]^[60]

Research Applications

Biomarker Use

ACTA2, encoding α-smooth muscle actin (α-SMA), serves as a key biomarker in immunohistochemistry (IHC) for identifying myofibroblasts, which are activated fibroblasts central to fibrotic processes and tumor microenvironments. In liver fibrosis, α-SMA staining via IHC detects hepatic stellate cell activation and myofibroblast differentiation, correlating with disease severity and progression in conditions like chronic hepatitis and cirrhosis.^[61] Similarly, in kidney fibrosis, IHC for α-SMA highlights interstitial myofibroblasts contributing to extracellular matrix deposition, aiding in the assessment of renal injury and chronic kidney disease staging.^[61] In tumor pathology, α-SMA IHC identifies cancer-associated fibroblasts (CAFs) in the stromal compartment, with high expression linked to poor prognosis in cancers such as colorectal and oral squamous cell carcinoma, where it indicates invasive potential and lymph node metastasis.^[62] Gene expression assays, particularly quantitative PCR (qPCR), utilize ACTA2 mRNA levels to monitor smooth muscle differentiation in stem cell-based therapies. In protocols for differentiating induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) into smooth muscle cells, upregulated ACTA2 expression via qPCR confirms successful lineage commitment, essential for applications in vascular tissue engineering and regenerative medicine.^[63] This approach provides a quantitative measure of differentiation efficiency, often alongside other markers like MYH11, to validate therapeutic cell populations. A notable limitation of ACTA2 as a biomarker is its non-specificity, as α-SMA expression occurs in various activated fibroblasts beyond disease-specific contexts, potentially confounding interpretations in heterogeneous samples like tumors or fibrotic tissues. As a marker of myofibroblast activation, its diagnostic value is enhanced when combined with context-specific assays.

Therapeutic Targets

Therapeutic strategies targeting ACTA2 focus on addressing pathogenic mutations that disrupt smooth muscle actin function, particularly in conditions like thoracic aortic aneurysm and dissection (TAAD) and multisystemic smooth muscle dysfunction syndrome (MSMDS). Gene therapy approaches, such as CRISPR-based editing, have shown promise in preclinical models by correcting specific ACTA2 mutations to restore normal actin polymerization and vascular integrity. For instance, adenine base editing using CRISPR/Cas9 delivered via adeno-associated virus has successfully targeted the common R179H mutation in ACTA2, reducing aortic dilation and improving smooth muscle cell contractility in humanized mouse models of MSMDS and TAAD.^[6] Similarly, customized CRISPR-Cas9 systems have repaired ACTA2 genetic errors in patient-derived smooth muscle cells, demonstrating restored protein function and potential for in vivo application in monogenic vascular diseases.^[64] These interventions aim to mitigate the dominant-negative effects of mutations, such as R179H, which impair actin filament assembly and lead to vascular pathology.^[65] Pharmacological interventions targeting upstream regulators of ACTA2, particularly the Rho kinase (ROCK) pathway, offer another avenue to modulate actin dynamics in ACTA2-related vascular disorders like Moyamoya disease, where mutations disrupt smooth muscle contractility and cerebral blood flow. ROCK inhibitors, such as fasudil, inhibit RhoA/ROCK signaling, which normally promotes actin-myosin interactions essential for vascular tone; the R258C mutation leads to defective polymerization, a process regulated by the RhoA/ROCK pathway.^[66] Fasudil has been shown to attenuate angiotensin II-induced abdominal aortic aneurysms by reducing ROCK-mediated actin stress fiber formation and proteolysis, suggesting applicability to ACTA2-associated thoracic aortic diseases.^[67] In the context of Moyamoya, where ACTA2 mutations are associated with occlusive cerebrovascular lesions, fasudil's vasodilatory effects via ROCK inhibition may have potential in managing vascular tone, though clinical translation remains exploratory.^[68] Stem cell-based therapies represent an emerging strategy to enhance α-SMA (encoded by ACTA2) expression for vascular tissue engineering, particularly in repairing ACTA2-deficient vessels. Induced pluripotent stem cells (iPSCs) can be differentiated into vascular smooth muscle cells (vSMCs) that upregulate α-SMA through targeted conditioning with growth factors or microRNAs, yielding contractile cells suitable for grafting in aneurysmal models.^[69] Adipose-derived stem cells, when integrated into engineered vascular constructs, significantly boost α-SMA levels and collagen maturation, improving tissue elasticity and mechanical strength for potential use in ACTA2-related aortic repair.^[70] These approaches leverage stem cell plasticity to compensate for mutant ACTA2 function, focusing on generating mature vSMCs that express high levels of α-SMA to support vascular homeostasis.^[71] As of 2025, clinical trials continue to evaluate beta-blockers as a medical management option for ACTA2-related thoracic aortic aneurysms, aiming to reduce hemodynamic stress on the aorta despite mixed evidence from broader TAA studies. Beta-blockers like propranolol lower aortic wall shear stress by decreasing heart rate and contractility, potentially slowing dilation in genetic aortopathies including those driven by ACTA2 mutations.^[72] A 2025 meta-analysis of randomized controlled trials in TAA patients found no overall reduction in clinical events with beta-blockers, prompting ongoing investigations into genotype-specific efficacy, such as in ACTA2 cohorts.^[73] Trials like the Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Registry (GenTAC) have informed these efforts by tracking outcomes in ACTA2 carriers under beta-blocker therapy, highlighting the need for tailored protocols.^[74]

References

[1]
ACTA2 gene: MedlinePlus Genetics
Jan 1, 2015 · The ACTA2 gene provides instructions for making a protein called smooth muscle alpha (α)-2 actin, which is part of the actin protein family.
[2]
Gene ResultACTA2 actin alpha 2, smooth muscle [ (human)] - NCBI
Sep 27, 2025 · This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, ...
[3]
ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA; ACTA2 - OMIM
Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.<|control11|><|separator|>
[4]
Aortic Disease Presentation and Outcome Associated With ACTA2 ...
Mar 10, 2015 · ACTA2 mutations are associated with high risk of presentation with an acute aortic dissection. The lifetime risk for an aortic event is only 76%.
[5]
Expanding the genetic and phenotypic spectrum of ACTA2-related ...
In addition, P variants in ACTA2 are associated with congenital heart diseases (eg, bicuspid aortic valve [BAV] and patent ductus arteriosus), iris flocculi, ...
[6]
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074218
[7]
The UMD-ACTA2 mutations database The gene
... (ACTA2) lies on chromosome 10 at 10q23.31 (Ueyama et al, 1990) This small gene (42 kb) is fragmented into 9 exons, transcribed in a 1,3 kb mRNA that encodes ...
[8]
ACTA2 Gene - GeneCards | ACTA Protein | ACTA Antibody
ACTA2 (Actin Alpha 2, Smooth Muscle) is a Protein Coding gene. Diseases associated with ACTA2 include Smooth Muscle Dysfunction Syndrome and Aortic Aneurysm.
[9]
Acta2 actin alpha 2, smooth muscle, aorta [ (house mouse)] - NCBI
In connective tissue fibroblasts, alpha-SMA is located within nuclear invaginations in close proximity to the nuclear membrane, but not in the ...Missing: ortholog | Show results with:ortholog
[10]
Myocardin-dependent Activation of the CArG Box-rich Smooth ... - NIH
One particularly strong SRF cofactor, myocardin (MYOCD), acts as a component of a molecular switch for smooth muscle cell (SMC) differentiation by activating ...
[11]
Myocardin is a master regulator of smooth muscle gene expression
May 19, 2003 · We show that myocardin, a cardiac muscle- and smooth muscle-specific transcriptional coactivator of SRF, can activate smooth muscle gene expression in a ...
[12]
Myocardin Is a Key Regulator of CArG-Dependent Transcription of ...
The interactions between serum response factor (SRF) and CArG elements are critical for smooth muscle cell (SMC) marker gene transcription.
[13]
ACTA2 protein expression summary - The Human Protein Atlas
ACTA2 is selectively expressed in smooth muscle and myoepithelial cells, tissue enhanced in smooth muscle, and group enriched in smooth muscle cells, ...
[14]
Smooth Muscle α Actin (Acta2) and Myofibroblast Function during ...
Smooth muscle α actin (Acta2) expression is largely restricted to smooth muscle cells, pericytes and specialized fibroblasts, known as myofibroblasts.
[15]
An α-Smooth Muscle Actin (acta2/αsma) Zebrafish Transgenic Line ...
One of the earliest markers of mural cell development in vertebrates is α smooth muscle actin (acta2; αsma), which is expressed by pericytes and SMCs. In vivo ...Missing: tissues | Show results with:tissues
[16]
Cardiac manifestations of human ACTA2 variants recapitulated in a ...
Feb 5, 2024 · Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.Results · Clinical Report · Acta2 Pathogenic Variants...
[17]
ACTA2 - Actin, aortic smooth muscle - Homo sapiens (Human)
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.<|control11|><|separator|>
[18]
The N-terminal Ac-EEED sequence plays a role in alpha-smooth ...
We have previously shown that the N-terminal sequence AcEEED of alpha-smooth-muscle actin causes the loss of alpha-smooth-muscle actin from stress fibers ...Missing: acetylation | Show results with:acetylation
[19]
NAA80 is actin's N-terminal acetyltransferase and regulates ... - PNAS
Mar 26, 2018 · We reveal that NAA80, a suggested NAT enzyme whose substrate specificity had not been characterized, is Nt-acetylating actin.
[20]
Bioinformatics analysis of proteins interacting with different actin ...
Moreover, actin isoforms have a high degree of sequence identity (∼93–99 %) and are structurally similar [6,15]. Cryoelectron microscopy studies of skeletal ...
[21]
Stable incorporation of α‐smooth muscle actin into stress fibers is ...
Jul 3, 2015 · The specific NH2-terminal sequence AcEEED of alpha-smooth muscle actin plays a role in polymerization in vitro and in vivo.
[22]
Structure and Dynamics of the Actin-Based Smooth Muscle ... - NIH
... alpha smooth muscle actin predominating in vascular smooth muscle and gamma ... myosin by way of further modulating tropomyosin on actin is not known.
[23]
α-Smooth Muscle Actin Is Crucial for Focal Adhesion Maturation in ...
α-SMA accelerates focal adhesion maturation, stabilizes them, and increases adhesion strength in myofibroblasts. Its incorporation into stress fibers is ...
[24]
Molecular phenotyping and functional assessment of smooth muscle ...
Migration velocity was impaired for ACTA2 and MYH11 cells. ACTA2 cells ... ACTA2 is essential for migration (34,35). Decreased contractility of ...
[25]
Actin alpha 2, smooth muscle, a transforming growth factor-β1 ...
ACTA2 is a marker of functional periodontal ligament (PDL) fibroblasts and is upregulated by transforming growth factor-β1 (TGF-β1); however, the underlying ...Missing: profile | Show results with:profile
[26]
[PDF] Alpha-Smooth Muscle Actin (α-SMA) - Journal of American Science
Alpha-smooth muscle actin (alpha-SMA) is the actin isoform that predominates ... Bundles play a role in many cellular processes such as cell division (cytokinesis) ...
[27]
Focal adhesion size controls tension-dependent recruitment of α ...
Jan 9, 2006 · The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts. Am. J ...
[28]
Regulation and Tuning of Smooth Muscle Myosin - ATS Journals
Contraction in smooth muscle is driven by the cyclic ATP-driven interaction of myosin and actin. While these proteins are not organized in sarcomeres as they ...
[29]
Actin cytoskeletal dynamics in smooth muscle: a new paradigm for ...
The activation of myosin by a contractile stimulus enables myosin filaments to crawl along actin filaments through the ATPase activity of the myosin head, thus ...
[30]
Critical role of actin-associated proteins in smooth muscle ...
Oct 30, 2015 · Myosin may serve as an “engine” for smooth muscle contraction whereas the actin cytoskeleton may function as a “transmission system” in smooth ...Inhibition Of Actin... · Role Of Abl Tyrosine Kinase... · Small Gtpases And Pak In...<|separator|>
[31]
Regulation of smooth muscle contraction - ScienceDirect.com
The actin-binding proteins caldesmon and calponin are phosphoproteins that inhibit actomyosin ATPase in vitro. Both have been hypothesized to be phosphorylated ...Missing: ACTA2 | Show results with:ACTA2
[32]
Functional interrelationship between calponin and caldesmon - PMC
Calponin and caldesmon, constituents of smooth-muscle thin filaments, are considered to be potential modulators of smooth-muscle contraction.Missing: ACTA2 | Show results with:ACTA2
[33]
Loss of Smooth Muscle α-Actin Leads to NF-κB–Dependent ...
Mutations in ACTA2, encoding the smooth muscle isoform of α-actin, cause thoracic aortic aneurysms, acute aortic dissections, and occlusive vascular diseases.
[34]
Genomic Editing of a Pathogenic Sequence Variant in ACTA2 ...
May 16, 2025 · The trimmed reads were aligned to the human genome (GRCh38) using STAR (v2.7.3a). Gene expression quantification was performed using the ...<|control11|><|separator|>
[35]
Angiotensin II stimulates alpha-skeletal actin expression ... - PubMed
Angiotensin II increases also the expression of alpha-smooth muscle actin in sarcomeres of cardiomyocytes as well as in fibroblastic cells present within the ...Missing: ACTA2 | Show results with:ACTA2
[36]
https://pubmed.ncbi.nlm.nih.gov/11776396/
[37]
Sustained Downregulation of Vascular Smooth Muscle Acta2 After ...
Mar 13, 2022 · Conclusion: A transient exposure to Ang II produces prolonged vascular remodeling with robust ACTA2 downregulation, associated with epigenetic ...
[38]
Global Expression Profiling of Fibroblast Responses to Transforming ...
The activation of fibroblasts by TGF-β is accompanied by their transformation into smooth muscle α-actin-expressing contractile myofibroblasts.
[39]
Similarities and Differences in Smooth Muscle α-Actin Induction by ...
Abstract—Transforming growth factor-β (TGF-β) has been shown to stimulate smooth muscle (SM) α-actin expression in smooth muscle cells (SMCs) and non-SMCs.<|control11|><|separator|>
[40]
Myofibroblasts Contribute to but are not Necessary for Wound ...
The overall expression of ACTA2, ACTB and ACTG1 (Figure 1C) was found to be significantly increased in contracted scar tissue when compared with unwounded human ...
[41]
Cancer-associated fibroblasts: an emerging target of anti ... - NIH
Aug 28, 2019 · One of the most dominant components in the tumor stroma is cancer-associated fibroblasts ... fibroblasts to drive cancer cell invasion. Nat Cell ...
[42]
Targeting myofibroblastic cancer-associated fibroblasts (myCAFs)
Mar 17, 2025 · ... ACTA2 expression ... Tumors enriched with myCAFs are strongly associated with reduced patient survival, as well as increased tumor invasion and ...
[43]
Endothelial-to-mesenchymal transition in cardiovascular disease - NIH
- ScRNA and ScATAC-seq showed DF-promotes EndMT with upregulated Acta2, Snai1, Tagln, Cnn1. ... - Using Lineage tracing mice, ECs were found to give rise to Fap + ...
[44]
Tumor Endothelial Cells with Distinct Patterns of TGFβ-Driven ...
Surprisingly, a number of TEC clones showed elevated basal mRNA expression of the EndMT and myofibroblast differentiation marker, SMA (Acta2; Fig. 1C). On the ...
[45]
Aortic Disease Presentation and Outcome Associated with ACTA2 ...
Mar 10, 2015 · Mutations in the ACTA2 gene are responsible for 12–21% of familial thoracic aortic disease without features of connective tissue disorders ...
[46]
Aortic Disease Presentation and Outcome Associated With ACTA2 ...
Mar 10, 2015 · ACTA2 mutations are associated with high risk of presentation with an acute aortic dissection. The lifetime risk for an aortic event is only ...
[47]
Multisystemic smooth muscle dysfunction syndrome
Multisystemic smooth muscle dysfunction syndrome ... A certain genetic change in the ACTA2 gene has been shown to cause this condition in some individuals.
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Multisystemic Smooth Muscle Dysfunction Syndrome - ACTA2 Alliance
While every cell in the body carries the same copy of the ACTA2 gene (code or “recipe”), only those that need to perform contraction in the organs and vessels ...
[49]
Clinical history and management recommendations of the smooth ...
Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy.
[50]
Mutations in Smooth Muscle Alpha-Actin (ACTA2) Cause Coronary ...
The nine exons and flanking intronic regions of ACTA2 were sequenced in 237 patients who were admitted for surgical repair of a thoracic aortic aneurysm or ...Missing: architecture | Show results with:architecture
[51]
A novel distinctive cerebrovascular phenotype is ... - PubMed - NIH
Jul 24, 2012 · Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features.
[52]
Mutations in smooth muscle alpha-actin (ACTA2) cause ... - PubMed
Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease · Abstract.
[53]
Two patients with the heterozygous R189H mutation in ACTA2 and ...
We describe two patients, a 3-day-old newborn and a 26-year-old woman, with this unique mutation in association with a huge PDA and an aorto-pulmonary window.
[54]
Smooth Muscle α-Actin Deficiency Leads to Decreased Liver ...
Aug 30, 2019 · The results demonstrating that knockout of SM α-actin leads to reduced liver fibrosis and COL1 expression.Missing: association | Show results with:association
[55]
Molecular Regulation of Arterial Aneurysms: Role of Actin Dynamics ...
Aug 9, 2017 · In vascular SMCs, α-actin (ACTA2) is the predominantly expressed actin isoform and the most abundant protein accounting for ~40% of the total ...Missing: tone | Show results with:tone
[56]
De novo ACTA2 mutation causes a novel syndrome of ... - PubMed
Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the ...Missing: R179 mechanism
[57]
Smooth Muscle-Alpha Actin R149C Pathogenic Variant ... - NIH
Jun 1, 2023 · This study tested the hypothesis that the Acta2 R149C/+ variant alters actin isoform expression and decreases integrin recruitment, thus, reducing aortic ...
[58]
Vascular disease-causing mutation, smooth muscle α-actin R258C ...
Jun 26, 2017 · We have implemented a human cell model to interrogate functional effects of mutant SM α-actin by inducing ACTA2 expression from endogenous genes ...Missing: profile | Show results with:profile
[59]
Immature Acta2R179C/+ smooth muscle cells cause moyamoya-like ...
Jul 2, 2025 · Here we show that Acta2 R179C/+ smooth muscle cells (SMCs) fail to fully differentiate and maintain stem cell-like features, including increased migration and ...
[60]
In vivo Treatment of a Severe Vascular Disease via a Bespoke ...
Nov 11, 2024 · Here, we explored genome editing to correct the most common MSMDS-causative mutation ACTA2 R179H. In a first-in-kind approach, we performed ...
[61]
In vivo Treatment of a Severe Vascular Disease via a Bespoke ... - NIH
Pathogenic missense mutations in the alpha actin isotype 2 gene (ACTA2) primarily affect smooth muscle cell (SMC) function and cause multisystemic smooth muscle ...
[62]
Vascular disease-causing mutation R258C in ACTA2 disrupts actin ...
The mutant actin shows multiple defects, including impaired interaction with myosin, formation of less stable filaments, and enhanced levels of monomer.Missing: hotspots | Show results with:hotspots
[63]
Fasudil, a Rho-kinase inhibitor, attenuates angiotensin II ... - PubMed
Fasudil treatment resulted in a dose-dependent reduction in both the incidence and severity of AAA. At the higher dose, fasudil decreased AAA by 45% while ...Missing: ACTA2 Moyamoya disease
[64]
Between Rho(k) and a Hard Place | Circulation Research
Feb 27, 2015 · Subsequent studies using the Rho kinase inhibitor Fasudil have shown that inhibition of Rho kinase reduces blood pressure and endothelial ...
[65]
Differentiation and Engineering of Human Stem Cells for Smooth ...
This review covers the various approaches involved in the regeneration of vascular smooth muscles by conditioning human stem cells.
[66]
Adipose-derived stem cells significantly increases collagen level ...
Sep 22, 2023 · ASCs increase elasticity of engineered vascular tissues ... ASC-based engineered tissues show marked αSMA expression and mature collagen.Missing: approaches | Show results with:approaches
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Induced pluripotent stem cell-derived vascular smooth muscle cells
Markers like TAGLN are expressed in SMCs and fibroblasts, while ACTA2 is expressed in both vSMCs and non-vSMCs (e.g., myofibroblasts, early cardiomyocytes).
[68]
Medical Therapy of Thoracic Aortic Aneurysms | Circulation
Sep 27, 2011 · In a small study of 70 patients with Marfan syndrome, propranolol-treated patients had a 73% lower rate of aortic dilatation and lower mortality ...
[69]
Efficacy of beta-blocker agents on clinical outcomes in patients with ...
Apr 10, 2025 · We found no evidence of benefit from β-blocker treatment for patients with TAA. More robust RCTs are needed to establish evidence-based ...Missing: ACTA2- related
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National Registry of Genetically Triggered Thoracic Aortic ...
GenTAC established a registry of 3706 patients with genetic conditions that may be related to thoracic aortic aneurysms and collected medical data and biologic ...