Caveolin-3 Promotes a Vascular Smooth Muscle Contractile Phenotype

Abstract

Epidemiological studies have demonstrated the importance of cardiovascular diseases in Western countries. Among the cell types associated with a dysfunctional vasculature, smooth muscle (SM) cells are believed to play an essential role in the development of these illnesses. Vascular SM cells are key regulators of the vascular tone and also have an important function in the development of atherosclerosis and restenosis. While in the normal vasculature, contractile SM cells are predominant, in atherosclerotic vascular lesions, synthetic cells migrate toward the neointima, proliferate, and synthetize extracellular matrix proteins. In the present study, we have examined the role of caveolin-3 in the regulation of SM cell phenotype. Caveolin-3 is expressed in vivo in normal arterial SM cells, but its expression appears to be lost in cultured SM cells. Our data show that caveolin-3 expression in the A7r5 SM cell line is associated with increased expression of contractility markers such as SM α-actin, SM myosin heavy chain but decreased expression of the synthetic phenotype markers such as p-Elk and Klf4. Moreover, we also show that caveolin-3 expression can reduce proliferation upon treatment with LDL or PDGF. Finally, we show that caveolin-3-expressing SM cells are less sensitive to apoptosis than control cells upon treatment with oxidized LDL. Taken together, our data suggest that caveolin-3 can regulate the phenotypic switch between contractile and synthetic SM cells. A better understanding of the factors regulating caveolin-3 expression and function in this cell type will permit the development of a better comprehension of the factors regulating SM function in atherosclerosis and restenosis.

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo

“…The mechanism of the phenotype switch is complicated and involves multiple factors. Myocardin and caveolin-3 were both identified as the guardians of a vascular smooth muscle contractile phenotype [31,32], whereas miR-143/145 and KLF4 promoted the SMC phenotype switch from a contractile to a synthetic state [12,14,33]. Although various data demonstrated that KLF4 is a key molecule regulating the SMC phenotype switch, the regulation of KLF4 expression is still unclear.…”

Caveolin as a Novel Potential Therapeutic Target in Cardiac and Vascular Diseases: A Mini Review

“…Moreover, Schwencke C et al [30] showed that the adenoviral overexpression of caveolin-1 inhibits smooth muscle cell proliferation and that the expression of caveolin-1 in vivo is significantly decreased in proliferating vascular smooth cells of human atheroma, suggesting that the loss of antiproliferative control by caveolin-1 plays a pivotal role in vascular smooth muscle cell proliferation during atherosclerosis. Furthermore, Gutierrez-Pajares JL et al [31] revealed that caveolin-3 promotes the contractile phenotype of vascular smooth muscle cells and reduces cell proliferation and migration, indicating that downregulating caveolin-3 contributes to atherosclerosis development or restenosis by promoting vascular dedifferentiation. Hence, modulating vascular smooth muscle remodeling is another mechanism through which caveolin regulates atherosclerosis.…”

Protective Role of Hydrogen Gas on Oxidative Damage and Apoptosis in Intestinal Porcine Epithelial Cells (IPEC-J2) Induced by Deoxynivalenol: A Preliminary Study

“…The protective effect of H 2 on cell viability was measured by the MTT assay. Lactate dehydrogenase (LDH) activity in the culture medium can indirectly indicate cell death/apoptosis [25,26]. As shown in Figure 2A and 2B, in the DON group, 5 µM DON significantly weakened cell viability (p < 0.05) and increased the release of LDH (p < 0.05) compared to the control group.…”

“…Cell culture supernatant was collected to assess lactate dehydrogenase (LDH) release due to cell death/apoptosis [25,26]. Briefly, IPEC-J2 cells (2 × 10 5 cells/well) were grown in six-well plates.…”