Serum Starvation and Growth Factor Receptor Expression in Vascular Smooth Muscle Cells

Abstract

Background: Smooth muscle cell (SMC) proliferation in atherosclerosis is regulated through the interaction of growth factors like platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) and their receptors (R). We hypothesized that serum starvation of SMCs may affect PDGFβ-R and IGF-1-R expression and, consequently, the effect of their cognate ligands on SMC survival/proliferation. Methods and Results: Serum starvation significantly increases PDGFβ-R but not IGF-1-R mRNA and protein expression in SMCs. PDGF-BB stimulates cell survival but not proliferation in serum-starved SMCs of the synthetic phenotype, whereas SMCs of the contractile phenotype respond to PDGF-BB by a significant increase in proliferation. Immunohistochemical analysis of coronary atherosclerotic lesions reveals PDGFβ-R expression in SMCs in the lamina fibromuscularis, but not in the media and in healthy parts of the arterial wall. No such differential expression was observed for IGF-1-R. Conclusions: Differential regulation of PDGFβ-R and IGF-1-R expression by serum starvation might represent a mechanism for the control of SMC survival/proliferation in atherogenesis and restenosis. The distribution of PDGFβ-Rs and IGF-1-Rs in atherosclerotic lesions may indicate an effect of serum starvation on SMCs in the arterial wall.

Autophagy in cardiovascular biology

“…PDGF-BB, which promotes development of the proliferative VSMC phenotype, is a robust inducer of autophagy (118). These results clearly contrast with the observation that both serum starvation and nutrient deprivation, standard inducers of autophagy, inhibit VSMC proliferation (119,120). Moreover, treatment of VSMC with the cortisone reductase inhibitor emodin induces growth arrest and cell death by autophagy (121).…”

Characterization of the chemotactic and mitogenic response of SMCs to PDGF‐BB and FGF‐2 in fibrin hydrogels

“…Additionally, we observed that the mitogenic response to these growth factors was partially dependent on the presence of serum. Observations from other groups which demonstrated altered PDGF receptor expression in cells cultured in the absence of serum factors may offer an explanation for these results 30. Second, the replicability of these results in other cell types, as well as to other species should be a consideration before application in other animal or human studies.…”

“…Observations from other groups which demonstrated altered PDGF receptor expression in cells cultured in the absence of serum factors may offer an explanation for these results. 30 Second, the replicability of these results in other cell types, as well as to other species should be a consideration before application in other animal or human studies. Finally, while fibrin is a commonly used hydrogel in tissue engineering for many applications, the possibility that these responses are specific to fibrin compared to other extracellular matrices should be considered.…”

Predicting Candidate Genes Based on Combined Network Topological Features: A Case Study in Coronary Artery Disease

“…Leptin-induced platelet activity required activation of a signaling cascade that included the long form of the leptin receptor, three kinases of JAK2, PI3K and PKB/Akt, IRS-1, and PDE3A. In addition, smooth muscle cell (SMC) proliferation in atherosclerosis was found [32] to mediate through the interaction of growth factors like platelet-derived growth factor-RB (PDGF-RB) and insulin-like growth factor-1 (IGF-1) and their receptors (R).…”