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OBJECTIVE: To investigate whether rs12731181 (A→G) interrupted miR-590-3p-mediated suppression of the prostaglandin F2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population. APPROACH AND RESULTS: We found that miR-590-3p regulates human FP gene expression by binding to its 3'-untranslated region. rs12731181 (A→G) altered the binding affinity between miR-590-3p and its FP 3'-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells. Overexpression of FP augmented vascular tone and elevated blood pressure in mice. An association study was performed to analyze the relationship between the FP gene and essential hypertension in the Han Chinese population. The results indicated that the rs12731181 G allele was associated with susceptibility to essential hypertension. Carriers of the AG genotype exhibited significantly higher blood pressure than those of the AA genotype. FP gene expression was significantly higher in human peripheral leukocytes from individuals with the AG genotype than that in leukocytes from individuals with the AA genotype. CONCLUSIONS: rs12731181 in the seed region of the miR-590-3p target site is associated with increased risk of essential hypertension and represents a new paradigm for FP involvement in blood pressure regulation.

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Objective: To assess whether the level of γ-glutamyltransferase(GGT) correlates with severity and stability of coronary atherosclerosis and other established cardiovascular risk factors. Methods: According to the results of coronary angiography, 132 patients with coronary heart disease(CHD) were selected to the CHD group. These patients were further divided into subgroups according to the clinical types, the number of diseased coronary branches. They were devided into one-vessel, two-vessel or three-vessel disease on the basis of the number of diseased coronary branches; were devided into stable angina pectoris and acute coronary syndrome according to the clinical types. 30 patients without CHD were selected to the control group. The level of GGT, white blood cell (WBC) count, total bilirubin(TBiL), fasting plasma glucose(FPG), total cholesterol (TC), triglyceride(TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL),glutamic-pyruvic transaminase(ALT), high sensitive C reactive protein(hs-CRP),systolic blood pressure(SBP), diastolic blood pressure(DBP), body mass index(BMI)were measured, and age, prior medical histories including hypertension? diabetes mellitus and smoking status were obtained. The level of GGT was compared statistically between the subgroups, and correlation coefficients of GGT level with other conventional risk factors for CHD were calculated. Results: The level of GGT in CHD patient was significantly higher than that in controls. The level of GGT increased with the increasing number of diseased coronary branches. No significant difference was found in the level of GGT between patients with acute coronary syndrome and stable angina pectoris. The level of GGT was positively correlated with TC, TG and LDL, weakly correlated with WBC count and FPG, not correlated with hs-CRP, negatively correlated with TBiL. HDL. Conclusion: The level of GGT is associated with pathological severity of coronary atherosclerosis and other established cardiovascular risk factors, though it is not associated with stability of pathological changes of the coronary artery. The plasma level of GGT may be an independent risk factor for CHD.

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OBJECTIVE: To investigate the effects of pravastatin, fosinopril and their combination on ventricular remodeling, cardiac function, tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and matrix metalloproteinases (MMPs) activities after myocardial infarction (MI) in rats. METHODS: Acute myocardial infarction (AMI) was established by ligation of the anterior descending coronary artery in male Sprague-Dawly (SD) rats. Twenty-four hours after the procedure, the 48 surviving rats were grouped randomly as AMI control, fosinopril (10 mg.kg(-1).d(-1)), pravastatin (20 mg.kg(-1).d(-1)) and a combined use of the 2 drugs. Sham-operated group (n = 8) was taken randomly as non-infarction control. Six weeks after treatment with the drugs by gastric gavage, heart function and left ventricular remodeling were assessed. Left ventricular weight (LVW)/body weight (BW) ratio was determined. The relative expression of myocardium TNF-alpha mRNA was assessed by reverse transcription-polymerase chain reaction. Left ventricular myocardium MMPs activities were assessed by Zymography. RESULTS: There were no significant differences among the four AMI groups in infarction size (P > 0.05). In comparison with the AMI group, left ventricular end-diastolic pressure, left ventricular end-diastolic diameter, LVW/BW all decreased significantly (P < 0.05 - 0.01); while dp/dtmax, dp/dtmin, fractional shortening (FS) and ejection fraction (EF) increased significantly in all three drug-treated groups (P < 0.05 - 0.01); increments of FS, LVEF and dp/dtmax were more evident in the combination group than either the fosinopril or pravastatin group (P < 0.05). The levels of TNF-alpha mRNA in AMI rats treated with fosinopril, pravastatin and their combination reduced 29%, 26% and 33%, respectively (P < 0.01); MMP-2 activity reduced 25%, 30% and 35%, respectively (P < 0.01); MMP-9 activity reduced 20%, 18% and 24%, respectively (P < 0.01). There were no significant differences in other variables among the 3 treatment groups (P > 0.05). CONCLUSION: Pravastatin, fosinopril and their combination showed favorable effects on left ventricular remodeling after AMI in rats and demonstrated improved cardiac function. The combined treatment group yielded better results in the context of improving left ventricular systolic function. These effects could be relevant to the attenuation of increased MMP-2 and MMP-9 activities and left ventricular expression of TNF-alpha.

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