Abstract
Atherosclerosis is an important pathological condition which is accompanied by a vascular smooth muscle cell (VSMC) phenotype switch toward a synthetic phenotype. As an acute-phase protein, Serum Amyloid A (SAA) is thought to have a close relationship to atherosclerosis development. However, no study has investigated the direct effect of SAA on the VSMC phenotype switch, as well as the underlying mechanisms. The purpose of our study was to explore the effect of SAA on the VSMC phenotype switch and the potential mechanisms involved. In our study, we found that SAA induced the VSMC phenotype switch which reduced expression of the smooth muscle cell (SMC) marker and enhanced expression of the matrix synthesis related marker. The proliferative ability of VSMCs was also increased by SAA treatment. Furthermore, our research found that SAA activated the ERK1/2 and p38 MAPK signaling pathways. Finally, by applying the ERK1/2 and p38 inhibitors, U0126 and SB203580, we demonstrated that the SAA-induced VSMC phenotype switch was p38-dependent. Taken together, these results indicated that SAA may play an important role in promoting the VSMC phenotype switch through the p38 MAPK signaling pathway.
Highlights
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the developed world
The Rat aortic smooth muscle cells (RASMCs) were treated with Serum Amyloid A (SAA) at indicated concentrations for 72 h. (a) mRNA expression of the smooth muscle cell (SMC) related gene (α-SMA, h1-calponin, and SM22α) and cellular retinol binding protein 1 (CRBP-1) was examined by qPCR analysis. (b) Expression of the smooth muscle cell (SMC) related markers (α-SMA, h1-calponin, and SM22α) and CRBP-1 was detected by Western blot analysis. (c) Statistical analysis of the Western blot results. (d) Expression of α-SMA, h1-calponin, and SM22α was detected by immunofluorescent staining. ∗P < 0.05, ∗∗P < 0.01 versus the control group
To further explore the role of SAA on the RASMC phenotype switch, RASMCs were treated with SAA (0, 5, 10, and 20 μg/ml) for 72 h and the mRNA and protein levels of the matrix synthesis related markers were detected by qPCR and Western blot
Summary
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the developed world. Atherosclerosis is an important pathological condition in the development and progression of CVD [1, 2]. It is accompanied by abnormal growth of VSMCs and extracellular matrix synthesis [3]. VSMCs are highly plastic, existing in different phenotypic states, such as contractile and synthetic phenotypes [3]. Synthetic VSMCs possess higher proliferative and extracellular matrix synthesis capacity and lose contractile ability [4]. In response to injury, the contractile VSMC phenotype switch (i.e., dedifferentiation) toward a synthetic phenotype is an important step which leads to vascular lesions [6]. Targeting the VSMC phenotype switch could be an important strategy in atherosclerosis therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
