PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated. In this meta-analysis, we explored the association of PCSK9 rs505151 and rs11591147 polymorphisms with serum lipid levels and cardiovascular risk by calculating the standardized mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CI). Pooled results analyzed under a dominant genetic model indicated that the PCSK9 rs505151 G allele was related to higher levels of triglycerides (SMD: 0.14, 95% CI: 0.02 to 0.26, P = 0.021, I2 = 0) and low-density lipoproteins cholesterol (LDL-C) (SMD: 0.17, 95% CI: 0.00 to 0.35, P = 0.046, I2 = 75.9%) and increased cardiovascular risk (OR: 1.50, 95% CI: 1.19 to 1.89, P = 0.0006, I2 = 48%). The rs11591147 T allele was significantly associated with lower levels of total cholesterol (TC) and LDL-C (TC, SMD: -0.45, 95% CI: -0.57 to −0.32, P = 0.000, I2 = 0; LDL-C, SMD: -0.44, 95% CI: -0.55 to −0.33, P = 0.000, I2 = 0) and decreased cardiovascular risk (OR: 0.77, 95% CI: 0.60 to 0.98, P = 0.031, I2 = 59.9) in Caucasians. This study indicates that the variant G allele of PCSK9 rs505151 confers increased triglyceride (TG) and LDL-C levels, as well as increased cardiovascular risk. Conversely, the variant T allele of rs11591147 protects carriers from cardiovascular disease susceptibility and lower TC and LDL-C levels in Caucasians. These findings provide useful information for researchers interested in the fields of PCSK9 genetics and cardiovascular risk prediction not only for designing future studies, but also for clinical and public health applications.

MiR-590-3p displays protective effects in some cardiovascular diseases. However, the mechanisms by which miR-590-3p regulates vascular smooth muscle cells (VSMCs) remain to be elucidated. In this study, we investigated the role of miR-590-3p/CD40/p21^Cip1 pathway in VSMCs. The alterations of miR-590-3p, CD40 and /p21^Cip1 were verified in atherosclerosis (AS) plaque and TNF-α treated VSMCs by quantitative Real-time PCR, EdU staining, wound healing test, and flow cytometry. The expression levels of miR-590-3p and p21^Cip1 were decreased, whereas CD40 was increased in the AS plaques . TNF-α is a critical contributor of atherosclerosis and induces VSMCs proliferation and migration by upregulating CD40 and downregulating p21^Cip1. miR-590-3p inhibits the proliferation and migration of VSMCs through up-regulating the expression of p21^Cip1 and down-regulating the expression of CDK2/cyclin E1 by targeting CD40. The TNF-α-induced alterations were partially reversed by exogenous miR-590-3p mimic.The TNF-α-induced proliferation and migration of VSMCs were also prevented by miR-590-3p mimic . Thus, our study revealed a mechanism by which miR-590-3p attenuates atherosclerosis by preventing TNF-α-induced VSMCs proliferation and migration.