ACTA2 Human
Description
Overview of ACTA2 Human
The ACTA2 gene (actin alpha 2) encodes smooth muscle alpha-2 actin, a 375-amino-acid protein critical for smooth muscle contraction and cytoskeletal integrity. It is part of the actin family, which regulates cell movement, organelle transport, and muscle tensing. ACTA2 is predominantly expressed in vascular smooth muscle cells, where it forms sarcomeres—the structural units enabling muscle contraction .
Genetic Mutations and Associated Diseases
Key Disease Associations
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Familial Thoracic Aortic Aneurysm and Dissection (TAAD): Over 30 ACTA2 mutations identified. Mutations disrupt sarcomere function, weakening the aortic wall and increasing susceptibility to dissection .
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Moyamoya Disease: Linked to R258C mutations, causing cerebrovascular occlusion and strokes .
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Venous Malformations: ACTA2 deficiency impairs vascular integrity, leading to tortuous veins and disorganized smooth muscle .
Biochemical and Cellular Dysregulation
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Cytoskeletal Disruption: Mutations like R258C reduce actin polymerization, impairing stress fiber formation and cell migration. In fibroblasts, this leads to defective matrix contraction .
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Epigenetic Modifications: Angiotensin II (Ang II) exposure induces sustained ACTA2 downregulation via H3K27me3 histone methylation, promoting vascular remodeling .
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Smooth Muscle Dysfunction: Mutant α-actin alters calcium signaling and myosin interaction, reducing contractile force .
Animal and Cellular Models
Clinical Outcomes
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Penetrance and Mortality: Aortic events occur in 65% of ACTA2 mutation carriers, with in-hospital mortality rates up to 9.5% for type A dissections .
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Age-Related Risk: Mean age at first aortic event is 49 years, emphasizing the need for early monitoring .
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Venous Malformations: ACTA2 knockdown in zebrafish disrupts vascular development, validating its role in congenital vascular anomalies .
Diagnostic Challenges
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Genetic Testing: ACTA2 mutations are detected via sequencing panels, though variants may remain undiagnosed in non-familial cases .
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Biomarkers: Reduced ACTA2 expression correlates with vascular malformations and aortic remodeling .
Diagnostic Approaches
Therapeutic Targets
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Epigenetic Modulators: Inhibitors of H3K27me3 to reverse ACTA2 silencing in Ang II-induced remodeling .
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Signaling Pathway Inhibitors: Target Hedgehog or Ephrin-B2 pathways to mitigate vascular malformations .
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Surgical Interventions: Aortic repair in TAAD, though post-operative mortality remains significant .
Product Specs
Product Science Overview
Actins exist in two main forms: G-actin (globular actin) and F-actin (filamentous actin). G-actin is the monomeric form, while F-actin forms helical polymers. Both forms are intrinsically flexible structures . ACTA2 specifically encodes the smooth muscle actin found in the aorta, which plays a crucial role in vascular contractility and blood pressure homeostasis .
ACTA2 is involved in the contractile apparatus of smooth muscle cells. It is essential for the contraction of vascular smooth muscle, which is critical for maintaining blood pressure and regulating blood flow . The protein is also associated with the TGF-β pathway, which enhances the contractile properties of hepatic stellate cells, leading to liver fibrosis and cirrhosis .
Mutations in the ACTA2 gene are linked to several vascular diseases. For instance, thoracic aortic aneurysms and dissections (TAAD) are often associated with mutations in this gene . Additionally, ACTA2 is used as a marker for myofibroblast formation, which is significant in wound healing and tissue repair .
Human recombinant ACTA2 is produced using recombinant DNA technology, which involves inserting the human ACTA2 gene into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein is used in various research applications, including studies on vascular diseases, smooth muscle function, and drug development.
