Smooth Muscle Alpha-Actin (ACTA2) angiopathy

David Goldemund M.D.
Updated on 14/01/2024, published on 05/12/2022

  • ACTA2 angiopathy is a vascular disease resulting from either occluded or enlarged arteries and can be caused by mutations in a single gene
  • the vascular smooth muscle cell-specific isoform of α-actin (ACTA2) is a significant component of the contractile apparatus throughout the arterial system (Guo, 2009)
  • heterozygous ACTA2 mutations can cause the inappropriate proliferation of SMCs ⇒ this may represent another pathogenetic pathway contributing to occlusive vascular disease
  • most cases are diagnosed in childhood and present with:
    • familial thoracic aortic aneurysms and dissections (TAAD)
    • premature onset of coronary artery disease (CAD)
    • premature ischemic strokes (including moyamoya angiopathy)
  • in addition to the recommended routine imaging of the aorta for aneurysms, ACTA2-mutation carriers should also be monitored for CAD and cerebrovascular occlusive disease


  • SMCs and myofibroblasts from affected individuals proliferate more rapidly in culture than control cells ⇒  increased SMCs proliferation leads to steno-occlusive disease
  • not all regions are affected; it is hypothesized that SMC proliferation depends on the presence of the mutation and an additional factor (vascular injury or increased biomechanical stress)

Clinical presentation

  • aortic disease
    • thoracic aortic aneurysm and dissection in childhood and young adulthood
    • patent ductus arteriosus
  • cerebrovascular disease
    • ischemic strokes/TIA
    • seizures
  • pulmonary arterial hypertension
  • peripheral arterial aneurysms
  • GI abnormalities
    • intestinal malrotation
    • gastroesophageal reflux (GER)
    • constipation

Diagnostic evaluation

Brain imaging (CT/MRI)

  • periventricular white matter lesions
  • border zone or territorial infarcts

Vascular imaging (CTA/MRA, neurosonology)

  • medium to large vessels stenosis or occlusion, proximal ICA segment dilation
  • intracranial multisegmental angiopathy (usually intracranial ICA)
  • thoracic aortic aneurysm or dissection

Genetic testing

  • mostly de novo mutations
  • in familiar forms, inheritance is autosomal dominant

Differential diagnosis


Acute stroke therapy

  • standard acute stroke treatment → Recanalization therapy

    • exclude aortic dissection before administration of a thrombolytic agent!

Prevention of cerebrovascular disease

  • standard medical therapy
    • antithrombotic drugs
    • in elderly patients, initiate aggressive treatment of vascular risk factors
      • address modifiable risk factors like hypertension, diabetes, smoking, and dyslipidemia to minimize the likelihood of cerebrovascular events
      • avoid hypotension in moyamoya angiopathy or severe large vessel stenosis
  • consider reconstructive procedures like PTA or bypass surgery in patients with severe symptomatic stenosis or moyamoya

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Smooth Muscle Alpha-Actin (ACTA2) angiopathy