Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction.

Statin treatment reduces cardiovascular risk. However, individuals with well-controlled low-density lipoprotein (LDL) levels may remain at increased risk owing to persistent high triglycerides and low high-density lipoprotein cholesterol. Because resveratrol promotes glucose metabolism and mitigates cardiovascular disorders, we explored its mechanism of protective action on high-fat-induced endothelial dysfunction. Human umbilical venous endothelial cells were treated with oxidized LDL (ox-LDL) in vitro. Endothelial function, cell survival, proliferation, migration, and oxidative stress were analyzed through western blots, quantitative polymerase chain reaction, ELISA, and immunofluorescence. ox-LDL induced endothelial cell apoptosis, proliferation arrest, and mobilization inhibition, all of which resveratrol reduced. ox-LDL suppressed the activities of mitochondrial respiration complex I and III and reduced levels of intracellular antioxidative enzymes, resulting in reactive oxygen species overproduction and mitochondrial dysfunction. Resveratrol treatment upregulated Bnip3-related mitophagy and prevented ox-LDL-mediated mitochondrial respiration complexes inactivation, sustaining mitochondrial membrane potential and favoring endothelial cell survival. We found that resveratrol enhanced Bnip3 transcription through hypoxia-inducible factor 1 (HIF1) and 5' AMP-activated protein kinase (AMPK). Inhibition of AMPK and HIF1 abolished resveratrol-mediated protection of mitochondrial redox balance and endothelial viability. Together, these data demonstrate resveratrol reduces hyperlipemia-related endothelial damage by preserving mitochondrial homeostasis.

A subset of circulating microRNAs is expressed differently in patients with myocardial infarction.

The objective of the present study was to analyze the differences in the plasma microRNA (miRNA) expression profiles between patients with myocardial infarction (MI) (with or without heart failure) and individuals in a normal control group using an miRNA array. Specific miRNAs were selected to explore novel circulating markers for MI and heart failure. A total of 15 patients with heart failure and 10 patients without heart failure following acute MI (AMI) were recruited as the AMI with heart failure (AMHF) and with no heart failure (AMNHF) groups, respectively. In addition, 10 patients with an older (≥ 1 year) MI with heart failure were selected as the old MI and heart failure (OMHF) group. Finally, 10 patients with normal coronary angiograms were recruited as the control (N) group. The plasma of peripheral venous blood was collected for miRNA array detection. In the AMHF group, the expression of 17 miRNAs was upregulated and the expression of 21 miRNAs was downregulated by >1.5-fold compared with that in the AMNHF group. Compared with the N group, the expression of miRNAs in the AMNHF group was upregulated in 38 and downregulated in 48 cases by >1.5-fold. Compared with the OMHF group, 13 miRNAs were upregulated and 43 were downregulated by >1.5-fold in the AMHF group. Significant differences in the miRNA expression profiles were observed between patients with different stages of heart failure following MI and individuals in the normal control group. These differences were determined using miRNA array analysis methods based on the peripheral blood plasma. Thus, the specific miRNAs identified in this study may be novel circulating markers for MI and heart failure.

[Effect of different doses of perindopril on myocardial energy expenditure in patients with heart failure following myocardial infarction].

OBJECTIVE: To investigate the changes of myocardial energy expenditure in patients with heart failure following myocardial infarction after treatment with different doses of perindopril. METHODS: Sixty-three patients with heart failure after myocardial infarction were treated with perindopril for 12 months at the doses of 4 mg (group N) and 8 mg (group H). Doppler imaging was used to measure the structural and systolic functional parameters before and after the treatment, and the circumferential end-systolic wall stress (cESS) and myocardial energy expenditure (MEE) were calculated. The biochemical indicators including serum creatinine and plasma NT-proBNP were detected before and after the treatment. RESULTS: The two groups had similar measurements before treatment. After 12 months of perindopril treatment, the patients in group N showed higher LA, LV, RA, RV, LVIDs, AD, cESS, lgNT-proBNP, and MEE with lower LVFS and LVEF than those in group H. Compared to those before treatment, LVFS and LVEF were increased and LA, LV, RA, RV, AD, LVIDs, LVMI, lgNT-proBNP and MEEm lowered after the 12-month treatment in group H. Significant changes were also found in the measured parameters except for PWTs, LVET, LVSV and LVFS in group N after the treatment. Bivariate analysis showed a significant positive correlation between MEE and lgNT-proBNP (r=0.513, P<0.01). CONCLUSION: A 12-month treatment with perindopril can suppress myocardial remodeling, improve left ventricular systolic function, and lower NT-proBNP and myocardial energy expenditure in patients with heart failure after myocardial infarction, and a higher dose can produce better results.

[Comparison of eight equations for estimating glomerular filtration rate in patients with cardiovascular diseases].

OBJECTIVE: To assess the diagnostic value of 8 equations using different variables for determining the estimated glomerular filtration rate (eGFR) in patients with cardiovascular diseases. METHODS: GFR was estimated in 208 patients with cardiovascular diseases by (99m)Tc-DTPA dynamic renal imaging, and the eGFR was derived from 8 equations using different variables. RESULTS: In patients with chronic kidney disease (CKD) stages 1-3, the eGFR calculated suing serum creatinine (SCr)-based equation was better correlated to GFR estimated by (99m)Tc-DTPA renal imaging than that derived from cystatin C (Cys C)-based equations, whereas in patients with CKD stages 4 and 5, the estimates by the latter equation showed a better correlation to GFR. Compared with (99m)Tc-DTPA renal imaging, MDRD-based equation and simple MDRD equation resulted in a higher eGFR in patients with CKD stages 4 and 5, the Rule equation had a lower eGFR in CKD stages 1 and 2, the Macisaac equation yielded a higher eGFR in CKD stages 2-5, and the Tan equation showed a higher eGFR in CKD stages 2 and 3. In patients with mild renal dysfunction, the Scr-based equation had a higher AUC(ROC) than Cys C-based equation, which was reversed in patients with severe renal dysfunction; the AUC(ROC) of the two equations were comparable in patients with moderate renal dysfunction. Compared with (99m)Tc-DTPA renal imaging, the modified MDRD equation and Arnal-Dade equation showed no significant difference in the eGFR in patients with CKD stages 1-5. CONCLUSION: Modified MDRD equation (or simple MDRD equation) and Arnal-Dade equation are superior to other calculation methods for estimating the GFR in Chinese patients with cardiovascular disease.

Effect of obstructive sleep apnea syndrome on serum C-reactive protein level, left atrial size and premature atrial contraction.

OBJECTIVE: To assess the changes of serum C-reactive protein (CRP) level, left atrial size and atrial premature contraction (PAC) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: This study involved 277 patients with OSAS diagnosed after an overnight polysomnography, who underwent a 24-h Holter electrocardiography and ambulatory blood pressure monitoring for detection of PAC. According to the apnea-hypopnea index (AHI), 137 patients with PAC identified from these patients were classified into 3 groups, namely the mild (5≥AHI<15), moderate (15≥AHI<30) and severe (AHI≥30) groups. Serum CRP level was assessed by a high-sensitivity radio-immunoassay. The left atrial diameter and echocardiographic parameters were recorded by transthoracic Doppler echocardiography (TTE). RESULTS: We found a high prevalence of PAC in these OSAS patients (137/277, 49.4%). Serum CRP was significantly higher in severe OSAS group (5.01∓4.68 mg/L) than in the moderate (3.03∓1.94 mg/L) and mild OSAS (2.98∓1.82 mg/L) groups (P=0.040 and 0.033, respectively). The left atrial diameter was significantly increased in severe OSAS group (40.1∓7.9 mm) as compared to that in moderate (37.9∓5.5 mm) and mild (33.7 ∓ 3.8 mm) groups (P=0.025 and 0.002, respectively). The severity of OSAS was positively correlated to both CRP (r=0.304, P=0.034) and left atrial diameter (r=0.411, P=0.003). After adjusting for gender, age and body mass index (BMI), a strong correlation was found between the left atrial diameter and CRP (r=0.594, P=0.0005). CONCLUSION: There is a high prevalence of PAC in OSAS patients. The progression of OSAS is associated with increased serum CRP level and left atrial size in patients with premature atrial complexes. Our study suggests that inflammation associated with OSAS might contribute to atrial structural and electrical remodeling in OSAS patients with PAC.

[Effects of losartan on left ventricular hypertrophy and plasma transforming growth factor-beta1 in elderly patients with hypertension].

OBJECTIVE: To investigate the effects of losartan on left ventricular hypertrophy (LVH) and plasma transforming growth factor-beta1 (TGF-beta1) in elderly patients with essential hypertension (EH). METHODS: The elderly patients with EH were divided into two groups, namely EH+LVH group and EH group according to the data of echocardiogram. The systolic and diastolic blood pressures of the patients were monitored. Plasma TGF-beta1 was measured before and after 6 months' treatment with losartan, and the relationship between TGF-beta1 and other index were analyzed. RESULTS: After 6 months' treatment, the blood pressure of EH+LVH group and EH group were significantly lowered (P<0.01). Significant improvement of IVSTd, LVPWd, E/A, and LVMI (P<0.01) and obvious reduction of plasma TGF-beta1 (P<0.01) occurred in EH+LVH group after 6 months' treatment. Correlation analyses indicated that the plasma TGF-beta1 level was positively correlated to LVMI (P<0.01). CONCLUSION: Losartan can reversed LVH in elderly patients with EH partially by lowering plasma TGF-beta1 level.

[Mechanisms of losartan for inhibition of myocardial fibrosis following myocardial infarction in rats].

OBJECTIVE: To investigate the effect of losartan on cardiac mineralocorticoid receptor (MR) mRNA in rats after acute myocardial infarction (AMI). METHOD: AMI was induced in male SD rats by ligation of the left coronary artery. The survived rats were randomly divided into AMI group, losartan group, and sham-operated group. The cardiac functions of the rats were assessed by echocardiogram and hemodynamics, and the contents of angiotensin II (Ang II) and aldosterone (Ald) in the myocardial tissues were determined by radioimmunoassay. The collagen density in the myocardial tissues were calculated by Masson's trichrome staining and the expression of MR mRNA were determined by real-time quantitative fluorescent PCR. RESULTS: Both the contents of AngII and Ald in the myocardial tissues increased significantly in AMI group compared with those in the sham-operated group (P<0.01). The expression of MR mRNA and collagen density in the myocardial tissues also increased significantly than that in sham-operated group (P<0.01). After four weeks of losartan treatment, the contents of AngII and Ald in the myocardial tissues decreased significantly (P<0.05) and the expression of MR mRNA was also considerably lowered (P<0.01) in comparison with those in the AMI group. Treatment with losartan also resulted in significant decrease of the collagen density in the myocardial tissues. CONCLUSIONS: Losartan may reduce reactive fibrosis not only by attenuating the Ald signaling pathway but also by decreasing the expression of MR.