Smooth muscle cells and the pathogenesis of cerebral microvascular disease (“angiomyopathies”)

Abstract

Many forms of human cerebral microvascular disease result from abnormal proliferation and/or degeneration of smooth muscle cells (SMC) in the vessel wall of arteries and arterioles. Human cerebral microvessel-derived smooth muscle cells (MV-SMC) in culture can be used to study the pathogenesis of microvascular disease. Primary cultures were established from nonneoplastic human brain specimens surgically resected and characterized as to their growth properties and phenotype. The cultures have been used to study various factors that may be relevant in the pathogenesis of microangiopathies, in particular cerebral amyloid angiopathy (CAA), to help determine mechanisms of SMC degeneration in these disorders. Factors investigated have included cellular growth rate, response to hypoxia and amyloidogenic peptides, and telomerase activity. MV-SMC appear to behave differently than aortic SMC with regard to proliferation and telomerase activity. These differences may play a role in the responses to MV-SMC in the evolution of CAA and other microangiopathies (cerebral arteriosclerosis/lipohyalinosis) and provide insight into mechanisms of degeneration of these cells within vessel walls.