Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR-335-5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling. METHODS: ACS-related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL-6, IL-1ß, TNF-α, MCP-1, ICAM-1, and VCAM-1 levels were tested in ACS mice. Additionally, Notch signaling-related genes and matrix metalloproteinases (MMPs) were measured after miR-335-5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined. RESULTS: miR-335-5p targeted JAG1 and mediated Notch signaling in ACS. miR-335-5p up-regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway-related genes, IL-6, IL-1ß, TNF-α, MCP-1, ICAM-1, VCAM-1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR-335-5p overexpression and Notch signaling inhibition. CONCLUSIONS: Overexpression of miR-335-5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling.

Atorvastatin alleviates left ventricular remodeling in isoproterenol-induced chronic heart failure in rats by regulating the RhoA/Rho kinase signaling pathway.

BACKGROUND: Chronic heart failure (CHF) is characterized by left ventricular dysfunction and altered autonomic control of cardiac function. This study aimed to investigate the effects of atorvastatin on left ventricular remodeling (LVR) and cardiac function in rats with isoproterenol-induced CHF and the possible mechanism. METHODS: An isoproterenol-induced CHF model was established in rata, which were subsequently treated with atorvastatin. Echocardiography, hemodynamic, and left ventricular mass indexes were assessed. The mRNA expression of RhoA, Rho kinase, and endothelial nitric oxide synthase (eNOS) was determined by RT-qPCR. The protein expression of myosin-binding subunit (MBS), MBS-P, eNOS, phosphorylated-eNOS, RhoA, and Rho kinase was measured by Western blot analysis. The relative activity of NADPH oxidase, ROS, and NO was assessed by ELISA. RESULTS: Isoproterenol-induced CHF rats treated with atorvastatin exhibited decreased left ventricular end-systolic dimension, left ventricular end-diastolic dimension, left ventricular end-diastolic pressure, left ventricular mass index, maximum fall rate of change in left ventricular pressure, heart rate (p < 0.001), expression of RhoA, Rho kinase, MBS and MBS-P (p < 0.01), and relative activity of NADPH oxidase, ROS and NO (p < 0.05) and increased left ventricular short axis fractional shortening, left ventricular end-systolic pressure, maximum rise rate of change in left ventricular pressure (p < 0.001) and expression of eNOS, and phosphorylated-eNOS ser1177 (all p < 0.05) compared with those of rats with isoproterenol-induced CHF. CONCLUSION: We demonstrated that atorvastatin inhibits LVR and improves cardiac function in rats with isoproterenol-induced CHF through inhibition of the RhoA/Rho kinase signaling pathway.

Ghrelin expression and significance in 92 patients with atrial fibrillation.

OBJECTIVE: Ghrelin is a polypeptide that is closely associated with many cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure. This article aims to understand the expression of ghrelin in patients with atrial fibrillation (AF). METHODS: A total of 182 patients with non-valvular heart diseases were recruited, among whom 92 had AF and 90 had sinus arrhythmia (SA). The serum ghrelin amount was tested by the ELASA method. Moreover, blood sugar, lipids, liver function, and renal function were tested. All recruited patients underwent echocardiographic examination following admission. Three cardiac cycles were observed under continuous exhalation. The left atrial diameter (LAD) and the left ventricular ejection fraction (LVEF) were measured and averaged. Patients with AF received conventional treatment, and the aforementioned parameters were re-measured after 8 weeks. The results were statistically analyzed. RESULTS: The serum ghrelin level in the patients in the AF group (199.55±79.59 pg/mL) was lower than that in the patients in the SA group (313.89±71.13 pg/mL, p<0.01), whereas the serum ghrelin level in those in the paroxysmal AF group (224.44±72.33 pg/mL) was higher than that in those in the persistent AF group (176.00±79.88 pg/mL, p<0.01). There was a positive correlation between the serum ghrelin level and LVEF in the patients in the AF group (r=0.704, p=0.046). After treatment, the serum ghrelin level and LVEF in the patients in the AF group significantly increased, whereas LAD decreased. CONCLUSION: The serum ghrelin level in patients with AF was reduced, and after treatment, it significantly increased. There was a positive correlation between the serum ghrelin level and LVEF in the patients in the AF group.