miR-96-5p Regulates Proliferation, Migration, and Apoptosis of Vascular Smooth Muscle Cell Induced by Angiotensin II via Targeting NFAT5.

BACKGROUND: Aberrant proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) are major pathological phenomenon in hypertension. MicroRNAs (miRNAs/miRs) serve crucial roles in the progression of hypertension. We aimed to determine the role of miR-96-5p in the proliferation, migration, and apoptosis of VSMCs and its underlying mechanisms. METHODS: Angiotensin II (Ang II) was employed to treat VSMCs, and the expression of miR-96-5p was detected by RT-qPCR. Then, miR-96-5p mimic was transfected into VSMCs. Cell Counting Kit-8 assay, flow cytometry, transwell assay, and wound healing assay were applied to measure proliferation, cell cycle, and migration of VSMCs. The expression of proteins associated with proliferation, migration, and apoptosis was assessed. A luciferase reporter assay was applied to confirm the target binding between miR-96-5p and nuclear factors of activated T-cells 5 (NFAT5). Subsequently, siRNA was used to silence NFAT5, and cell proliferation, migration, and apoptosis were assessed. RESULTS: The results revealed that the expression of miR-96-5p was downregulated in Ang II-induced VSMCs. MiR-96-5p overexpression inhibited cell proliferation and migration but promoted cell apoptosis, enhanced the percentages of cells in the G1 and G2 phases, and reduced those in the S phase, accompanied by changes in the expression associated proteins. NFAT5 was confirmed as a direct target of miR-96-5p. NFAT5 silencing had the same results with miR-96-5p overexpression on VSMC proliferation, migration, and apoptosis, whereas miR-96-5p inhibitor reversed these effects. CONCLUSIONS: Our findings concluded that miR-96-5p could regulate proliferation, migration, and apoptosis of VSMCs induced by Ang II via targeting NFAT5.

Complement Components sC5b-9 and CH50 Predict Prognosis in Heart Failure Patients Combined With Hypertension.

BACKGROUND: Heart failure (HF), resulting from inflammation and vessel injury, is one of the leading causes of poor quality of life and premature death. The complement system plays a leading role in vessel integrity and inflammation response. However, the association between serum complement level and the prognosis of HF remains unclear. METHODS: In our study, a total of 263 newly diagnosed hypertension patients with HF were included. Eight classical cardiovascular risk factors were collected, and plasma C3a, C3b, C5a, sC5b-9, and CH50 levels were detected. RESULTS: Compared with the control group, plasma C5a (P<0.001), sC5b-9 (P<0.001), and CH50 (P = 0.004) levels of hypertension patients with HF were significantly increased. On the basis of univariate analysis, an older age, higher frequency of alcohol consumption, high level of body mass index, medium or high risk of hypertension, hyperlipidemia, and diabetes were poor prognostic factors whereas low levels of C5a, sC5b-9, and CH50 were associated with favorable overall survival (OS). When these factors fit into a multivariate regression model, patients with hyperlipidemia (P = 0.002, hazard ratio [HR] = 3.09), N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) ≥ 14.8 (P < 0.001, HR = 11.14), sC5b-9 level ≥ 1,406.2 µg/ml (P = 0.180, HR = 5.51) or CH50 level ≥ 294.6 µg/ml (P < 0.001, HR = 4.57) remained statistically factors for worsened OS and regarded as independent risk factors. These independently associated risk factors were used to form an OS estimation nomogram. Nomogram demonstrated good accuracy in estimating the risk, with a bootstrap-corrected C index of 0.789. CONCLUSIONS: sC5b-9 and CH50 levels are increased in hypertension patients with HF. Nomogram based on multivariate analysis has good accuracy in estimating the risk of OS.