Background: Studies have demonstrated that long noncoding RNAs (lncRNAs) have essential impacts on the development of atherosclerosis (AS). This study aimed to identify the role and functional mechanism of lncRNA CASC2 in the development and migration of vascular smooth muscle cells (VSMCs). Method: The serum of 40 pairs of AS patients and healthy volunteers were collected and the expression of CASC2 was evaluated. qRT-PCR and western blotting were carried out to examine the expression levels of at mRNA and protein level, repectively. Cell proliferation assay, colony formation assay, transwell migration assay, dual-luciferase reporter assay, and wound healing assay were conducted to evaluate cell proliferation, colony formation, migration, transcription, targeting, and self-restoration. Results: The expression levels of CASC2 were decreased, while the expression levels of miR-532-3p were elevated in AS patient samples and VSMCs. Overexpression of CASC2 inhibited the proliferation and migration of VSMCs and enhanced cell apoptosis. CASC2 inhibited the expression of miR-532-3p, and inversely upregulated the expression of PAPD5, which was a target of miR-532-3p. In addition, knockdown of miR-532-3p-mimic and PAPD5 could attenuate the impact of overexpression of CASC2 on proliferation, migration, and apoptosis in ox-LDL-VSMCs. Conclusion: CASC2 suppressed cell reproduction and promoted cell apoptosis by regulating the miR-532-3p/ PAPD5 axis in ox-LDL-mediated VSMCs. This might be important for AS therapeutics.
Urotensin II (UII), a vital vasoconstrictor peptide, causes an inflammatory response in the pathogenesis of atherosclerosis. Previous studies have reported that the Ras homolog gene family, member A (RhoA)/Rho kinases (ROCK) pathway modulates the inflammatory response of the atherosclerotic process. However, to the best of our knowledge, whether the RhoA/ROCK pathway mediates the inflammatory effect of UII has not been previously elucidated. Salidroside and isorhamnetin are two early developed antioxidant Tibetan drugs, both displaying cardioprotective effects against atherosclerosis. Therefore, the aim of the present study was to investigate the protective effects of salidroside, isorhamnetin or combination of these two drugs on the UII-induced inflammatory response in vivo (rats) or in vitro [primary vascular smooth muscle cells (VSMCs)], as well as to examine the role of the RhoA/ROCK pathway in these processes. The levels of inflammatory markers were measured via ELISA. The mRNA and protein expression levels of RhoA and ROCK II were detected using reverse transcription-quantitative PCR assay and western blot analysis. It was demonstrated that salidroside, isorhamnetin and both in combination decreased the levels of the serum pro-inflammatory cytokines TNF-α and IL-1β, as well as increased the levels of the anti-inflammatory cytokine IL-10 and macrophage migration inhibitory factor in rats with subacute infusion of UII and in the culture supernatant from primary VSMCs-exposed to UII. Moreover, salidroside, isorhamnetin and both in combination attenuated the mRNA and protein expression levels of RhoA and ROCK II in vivo and in vitro , at concentrations corresponding to human therapeutic blood plasma concentrations. Thus, these drugs could inhibit the RhoA/ROCK II pathway under UII conditions. The combination of salidroside and isorhamnetin did not display a stronger inhibitory effect on the inflammatory response and the RhoA/ROCK II pathway compared with salidroside and isorhamnetin in isolation. Collectively, the results indicated that salidroside, isorhamnetin and both in combination inhibited the RhoA/ROCK II pathway, which then attenuated the inflammatory response under UII-induced conditions, resulting in cardioprotection in atherosclerosis.
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