Abstract
Aims The main treatment for coronary heart disease is percutaneous coronary intervention (PCI), and drug-eluting stents are designed to inhibit vascular smooth muscle cell (VSMCs) proliferation and migration causing restenosis by releasing pharmacological agents into the vessel wall. Once drug-eluting stents are deployed, these pharmacological agents exert many biological effects in the coronary circulation, not only inhibition of VSMCs but also extension to vascular endothelial cells (VECs). The purpose of this study was to explore target molecules that inhibit VSMCs proliferation without affecting VECs. Methods mRNA and protein expressions of transient receptor potential channels (TRPCs) in cultured VSMCs and VECs were determined by western blotting and RT-qPCR. VSMCs and VECs proliferation was evaluated using CCK-8 assays and western blotting of proliferating cell nuclear antigen (PCNA). Calcium backfilling assays were performed to detect intracellular calcium ion concentration in cultured VSMCs and VECs. Results The TRPC6 expression was more abundant in VECs than VSMCs, while TRPC4 and TRPC5 expressions were more abundant in VSMCs than VECs. Knockdown of TRPC4 or TRPC5 alone had no remarkable inhibitory effect on VSMC proliferation. Synergistic knockdown of TRPC4 and TRPC5 inhibited the proliferation of VSMCs, declined the expression of the PCNA, and reduced the intracellular calcium ion concentration but not VECs. Conclusion These data suggest that concurrent inhibition of TRPC4 and TRPC5 inhibits VSMCs proliferation without affecting VECs, thus providing novel targets for developing pharmacological agents for drug-eluting stents.
Highlights
In recent years, coronary heart disease has become one of the major diseases endangering human health, and percutaneous coronary intervention (PCI) remains the main treatment [1]
Real-Time qPCR (RT-qPCR) results (Figure 1(a)) showed that mRNA expression levels of TRPC1 and TRPC6 were higher in vascular endothelial cells (VECs) than vascular smooth muscle cells (VSMCs)
TRPC4 and TRPC5 were significantly differentially expressed in VECs and VSMCs. e expression of TRPC4 and TRPC5 was higher in VSMCs than VECs. e results of this study indicate that, in human coronary artery smooth muscle cells and endothelial cells, downregulation of TRPC4 and TRPC5 can inhibit the proliferation of VSMCs without affecting the proliferation of VECs
Summary
Coronary heart disease has become one of the major diseases endangering human health, and percutaneous coronary intervention (PCI) remains the main treatment [1]. Drug-eluting stents are the most widely used stents in clinical practice due to their inhibition on proliferation and migration of vascular smooth muscle cells (VSMCs) and prevention on restenosis by releasing pharmacological agents into the vessel wall [2, 3]. E study aimed to develop novel drug-eluting therapies that could reduce the time needed for treatment. Previous studies have shown that TRPC and NCX together regulate the proliferation of VSMCs [15], but it is not clear whether SOC and NCX influence both smooth muscle cells and endothelial cells. To this end, we explored differences in the expression of TRPCs in VSMCs and VECs to identify target molecules that inhibited the proliferation of VSMCs without affecting the proliferation of VECs
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