Gene expression and vascular smooth muscle cell phenotype.

Vascular smooth muscle cells (VSMCs) are involved in a number of vascular disease processes including hypertension and atherosclerosis. However, their role in the pathogenesis of vascular disease is largely undetermined. We and others have studied rat VSMCs in cell culture as a model for VSMC behaviour in vivo. In recent experiments we have applied molecular biological techniques to compare genes expressed by normal contractile VSMCs with those expressed by VSMCs which have undergone several passages in cell culture. Using differential screening of a cDNA library derived from cultured rat aortic VSMC RNA we identified seven genes which are preferentially expressed by contractile VSMCs; alpha-smooth muscle actin, gamma-smooth muscle actin, calponin, phospholamban, tropoelastin, SM22 alpha and CHIP28, and two which are preferentially expressed in passaged cells which have down-regulated their contractile proteins; osteopontin (OP) and matrix Gla protein (MGP). In situ hybridization studies have confirmed that calponin and SM22 alpha, are highly expressed by medial VSMCs in human coronary arteries with little or no expression in the atheromatous intima whilst the converse is true for OP and MGP. Studies by ourselves and others have confirmed that OP is a marker for proliferating rat VSMCs both in vitro and in vivo. However, the evidence that OP is expressed by proliferating human VSMCs is less convincing.