Vascular smooth muscle cell differentiation in human cerebral vascular malformations

The pathogenesis of central nervous system vascular malformations likely involves the abnormal assembly, differentiation of vascular smooth muscle cells (VSMC), or both in association with dysmorphic vessel wall. We hypothesize that intracranial arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) exhibit distinct patterns of expression of molecular markers of differentiation and maturity of VSMCs. We further speculate that the unique VSMC phenotype in the different lesions is not necessarily maintained in cell culture. Paraffin-embedded sections of five AVMs, CCMs, and control brain tissues were stained immunohistochemically with antibodies to alpha-smooth muscle actin (alpha-SMA), myosin heavy chain, and smoothelin, a novel marker for contractile VSMC phenotype. Large (> or =100 microm) and small (