Statistical analysis Statistical significance no between samples was determined using the homoscedastic Students t test in two tailed distribution. Values of p 0. 05, p 0. 01 and p 0. 001 are indicated. If no specification is denoted in the legends, mean values SD from Inhibitors,Modulators,Libraries at least three independ ent experiments are depicted. Some figures display mean values from one representative out of three independent experiments. This is due to variations in the basal pro moter activity or viral propagation between the different repeats while the findings are comparable. In these cases, mean values SD are calculated from three bio Inhibitors,Modulators,Libraries logical replicates. Background Vascular smooth muscle cells in the tunica media of the arteries play important roles in regulating blood pres sure and vascular tone.
In normal vessels, these VSMCs exhibit a quiescent and differentiated phenotype and ex press proteins involved in the contractile functions such as smooth muscle Inhibitors,Modulators,Libraries myosin heavy chain and SM actin. However, in contrast to striated muscle cells, adult VSMCs retain significant plasticity, known as phenotypic modula tion. In response to arterial injury, VSMCs de differentiate, downregulate SM marker genes, and change to a prolifera tive and migratory phenotype, leading to lesion formation and occlusive vascular disease. Thus, preventing this de differentiation might be a potential therapeutic strategy for treating vascular disease. Cysteine rich protein 2, a LIM only CRP fam ily member, is highly expressed in VSMCs. F Importantly, balloon or wire artery injury reduces CRP2 expression, suggesting Inhibitors,Modulators,Libraries a critical role for CRP2 in the response to vascular injury.
By gene dele tion experiments, we demonstrated that a lack of CRP2 enhanced VSMC migration into the intima and in creased neointima formation following arterial injury. Our recent study determined that CRP2 sequesters the scaffold protein p130Cas at focal adhesions, Inhibitors,Modulators,Libraries con trols lamellipodia formation and reduces cell motility. These CRP2 p130Cas complexes function to blunt VSMC migration. Therefore, maintaining or upregu lating CRP2 expression during vascular injury might serve as a protective mechanism against intimal thickening. The multifunctional cytokine TGFB contributes to the pathogenesis of atherosclerosis and restenosis. During progressive intimal thickening following balloon angio plasty, neointimal SMCs produce TGFB and it acts as a growth regulatory factor.
selleck chemicals The importance of this auto crine TGFB pathway in vascular disease was established through studies selectively inhibiting TGFB mRNA in a rat vascular injury model in vivo, which resulted in blunted neointimal formation. Some of the effects of TGFB in VSMCs are controversial. For example, serum concentra tions of active TGFB are significantly reduced in patients with advanced atherosclerosis, suggesting TGFB is a key in hibitor of atherosclerosis.
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