Ze-Mu Wang

Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease

BackgroundHyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia.MethodsIn the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance.ResultsOur results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma.ConclusionsOur results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.

Black and green tea consumption and the risk of coronary artery disease: a meta-analysis

BACKGROUND Epidemiologic studies are inconsistent regarding the association between tea consumption and the risk of coronary artery disease (CAD). OBJECTIVE The objective was to perform a meta-analysis to determine whether an association exists between tea consumption and total CAD endpoints in observational studies. DESIGN We searched PUBMED and EMBASE databases for studies conducted from 1966 through November 2009. Study-specific risk estimates were combined by using a random-effects model. RESULTS A total of 18 studies were included in the meta-analysis: 13 studies on black tea and 5 studies on green tea. For black tea, no significant association was found through the meta-analysis [highest compared with lowest, summary relative risk (RR): 0.92; 95% CI: 0.82, 1.04; an increment of 1 cup/d, summary RR: 0.98; 95% CI: 0.94, 1.02]. For green tea, the summary RR indicated a significant association between the highest green tea consumption and reduced risk of CAD (summary RR: 0.72; 95% CI: 0.58, 0.89). Furthermore, an increase in green tea consumption of 1 cup/d was associated with a 10% decrease in the risk of developing CAD (summary RR: 0.90; 95% CI: 0.82, 0.99). CONCLUSIONS Our data do not support a protective role of black tea against CAD. The limited data available on green tea support a tentative association of green tea consumption with a reduced risk of CAD. However, additional studies are needed to make a convincing case for this association.

Association of polymorphisms in long non-coding RNA H19 with coronary artery disease risk in a Chinese population.

H19 is an imprinted gene transcribing a long non-coding RNA and is downregulated postnatally. Re-expression of H19 has been observed in patients with atherosclerosis. However, to date, no data has been published on the association of H19 polymorphisms with the risk of coronary artery disease (CAD). In this study, four polymorphisms, rs217727, rs2067051, rs2251375, rs4929984, were analyzed in 701 CAD patients and 873 age- and sex-matched control subjects. Polymorphisms were genotyped by TaqMan technology. Our data showed that the T variant of rs217727 was associated with an increased risk of CAD [additive model: odds ratio (OR)=2.05, 95%CI=1.35-3.12; dominant model: OR=1.46, 95% confidence interval (CI)=1.12-1.90; recessive model: OR=1.75, 95%CI=1.18-2.58], while A variant of rs2067051 was associated with a decreased risk of CAD (additive model: OR=0.66, 95%CI=0.45-0.96; recessive model: OR=0.71, 95%CI=0.50-0.99). Combined analysis showed that subjects carrying 3 or 4 risk alleles had a significantly increased risk of CAD, relative to those with 0-2 risk alleles (OR=1.61, 95%CI=1.20-2.15). Moreover, CAD patients with 3 or 4 risk alleles also had significantly higher Gensini scores than those with 0-2 risk alleles (P=0.001). Further haplotype-based analysis revealed that individuals with C-G-C-C, T-G-A-A, and T-A-A-A haplotypes indicated a higher prevalence of CAD (OR=1.88, 95%CI=1.03-3.43; OR=2.26, 95%CI=1.19-4.31; OR=2.66, 95%CI=1.34-5.25, respectively), compared to individuals with the most common C-G-A-C haplotype. In conclusion, our study demonstrates for the first time that common polymorphisms of H19 are associated with the risk and severity of CAD in a Chinese population. Future studies are needed to explore the underlying mechanisms of our findings.

Flavonol intake and stroke risk: A meta-analysis of cohort studies

OBJECTIVE Epidemiologic findings are inconsistent regarding the association between flavonol intake and the risk for stroke. The aim of this study was to determine whether an association exists between them in observational studies. METHODS We searched the PubMed and EMBASE databases for studies conducted from 1966 to August 2013. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between flavonol intake and risk for stroke were included. A random effects model was used to combine study-specific risk estimates. RESULTS The meta-analysis included eight studies, with 5228 stroke cases among 280 174 participants. The summary RR indicated a significant association between highest flavonol intake and reduced risk for stroke (summary RR, 0.86; 95% CI, 0.75-0.99). Furthermore, an increase in flavonol intake of 20 mg/d was associated with a 14% decrease in the risk for developing stroke (summary RR, 0.86; 95% CI, 0.77-0.96). Subgroup analyses suggested a significant inverse association between highest flavonol intake and stroke risk among men (summary RR, 0.74; 95% CI, 0.56-0.97) but not women (summary RR, 0.99; 95% CI, 0.85-1.16). CONCLUSIONS Higher dietary flavonol intake is associated with a reduced risk for stroke, especially among men. Our results support recommendations for higher consumption of flavonol-rich foods to prevent stroke.

Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies

OBJECTIVE Findings from epidemiologic studies of coffee consumption and risk for cognitive decline or dementia are inconclusive. The aim of this study was to conduct a meta-analysis of prospective studies to assess the association between coffee consumption and the risk for cognitive decline and dementia. METHODS Relevant studies were identified by searching PubMed and Embase databases between 1966 and December 2014. Prospective cohorts that reported relative risk (RRs) and 95% confidence intervals (CIs) for the association of coffee consumption with dementia incidence or cognitive changing were eligible. Study-specific RRs were combined by using a random-effects model. RESULTS Eleven prospective studies, including 29,155 participants, were included in the meta-analysis. The combined RR indicated that high coffee consumption was not associated with the different measures of cognitive decline or dementia (summary RR, 0.97; 95% CI, 0.84-1.11). Subgroup analyses suggested a significant inverse association between highest coffee consumption and the risk for Alzheimer disease (summary RR, 0.73; 95% CI, 0.55-0.97). The dose-response analysis, including eight studies, did not show an association between the increment of coffee intake and cognitive decline or dementia risk (an increment of 1 cup/d of coffee consumed; summary RR, 1.00; 95% CI, 0.98-1.02). CONCLUSIONS The present study suggests that higher coffee consumption is associated with reduced risk for Alzheimer disease. Further randomized controlled trials or well-designed cohort studies are needed to determine the association between coffee consumption and cognitive decline or dementia.

Folate and risk of coronary heart disease: A meta-analysis of prospective studies

BACKGROUND AND AIMS Epidemiologic studies are inconsistent regarding the association between folate and coronary heart disease (CHD) risk. The aim was to perform a meta-analysis to determine whether an association exists between folate and total CHD endpoints in prospective studies. METHODS AND RESULTS We searched the PUBMED and EMBASE databases for studies conducted from 1966 through August 2010. Data were independently abstracted by 2 investigators using a standardized protocol. Study-specific risk estimates were combined by using a random effects model. A total of 14 studies were included in the meta-analysis: 7 studies on dietary folate intake and 8 studies on blood folate levels. For dietary intake, the summary relative risk (RR) indicated a significant association between the highest folate intake and reduced risk of CHD (summary RR: 0.69; 95% CI: 0.60, 0.80). Furthermore, an increase in folate intake of 200 ug/day was associated with a 12% decrease in the risk of developing CHD (summary RR: 0.88; 95% CI: 0.82, 0.94). For blood folate levels, we also found a borderline inverse association of highest blood folate levels on CHD risk (summary RR: 0.74; 95% CI: 0.53, 1.02); our dose-response analysis indicated that an increment in blood folate levels of 5 mmol/l was associated with an 8% decrease in the risk of developing CHD (summary RR: 0.92; 95% CI: 0.84, 1.00). CONCLUSION This meta-analysis suggests that dietary folate intake and blood folate level are inversely associated with CHD risk.

Magnesium intake and incidence of stroke: meta-analysis of cohort studies.

BACKGROUND AND AIMS Prospective cohort studies are inconsistent regarding the association between magnesium intake and the risk of stroke. The objective was to perform a meta-analysis to summarise the relationship between magnesium intake and risk of stroke in observational studies. METHODS AND RESULTS We searched the PubMed and EMBASE databases for studies conducted from 1966 through August 2011. Prospective studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between magnesium intake and the risk of total stroke incidence or mortality were included. Data were independently abstracted by two investigators using a standardised protocol. Study-specific risk estimates were combined by using a random effects model. A total of eight studies, with 8367 stroke cases among 304,551 participants, were included in the meta-analysis. The summary RR indicated a significant association between the highest magnesium intake and reduced risk of total stroke (summary RR: 0.89; 95% CI: 0.82, 0.97); our dose-response analysis showed a borderline inverse association between magnesium intake and total stroke risk (an increment of 100 mg day(-1); summary RR: 0.98; 95% CI: 0.95, 1.00). Subgroup analyses suggested a significant inverse association between highest magnesium intake and the risk of ischaemic stroke (summary RR: 0.88; 95% CI: 0.80, 0.98). CONCLUSION The present meta-analysis of prospective cohorts suggests that higher magnesium intake is associated with reduced risk of total and ischaemic stroke. However, well-designed randomised controlled trials are needed to draw a definitive conclusion.

Green tea polyphenol epigallocatechin-3-gallate inhibits TNF-α-induced production of monocyte chemoattractant protein-1 in human umbilical vein endothelial cells.

Aims: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, displays a variety of pharmacological properties and recently received attention as a prospective dietary intervention in cardiovascular diseases (CVD). This study was conducted to test the hypothesis that EGCG was able to inhibit tumor necrosis factor-a (TNF-a)-induced production of monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) and investigated the underlying molecular mechanisms. Methods: The inhibitory effect of EGCG on TNF-a-induced expression of MCP-1 was measured using ELISA and RT-qPCR. The effect of EGCG on TNF-a-induced nuclear factor-kappa B (NF-κB) activation was investigated by western blot and luciferase assays. Monocyte adhesion assay was detected by microscope. Results: EGCG significantly suppressed the TNF-a-induced protein and mRNA expression of MCP-1. Investigation of the mechanism suggested that EGCG suppressed the TNF-a-mediated NF-κB activation. In addition, the 67-kD laminin receptor (67LR) was involved in EGCG-mediated suppression of MCP-1 generation. Furthermore, EGCG potently inhibited monocyte adhesion to activated HUVECs. Conclusion: EGCG suppresses TNF-a-induced MCP-1 expression in HUVECs. This effect was mediated by 67LR and was via the inhibition of NF-κB activation. Our results demonstrated that EGCG might be a possible medicine for CVD prevention and treatment.

Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction.

Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nuclear factor (NF)-κB. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.

Flavonols intake and the risk of coronary heart disease: a meta-analysis of cohort studies

OBJECTIVE Prospective cohort are inconsistent regarding the association between flavonols intake and the risk of coronary heart disease (CHD). The aim was to perform a meta-analysis to determine whether an association exists between them in observational studies. METHODS We searched PUBMED and EMBASE databases for studies conducted from 1966 through January 2012. Data were independently abstracted by 2 investigators using a standardized protocol. Study-specific risk estimates were combined by using a random-effects model. RESULTS A total of nine general population cohorts with 216,908 participants and more than 5249 CHD cases were included in the meta-analysis. The summary relative risk (RR) did not indicate a significant association between the highest flavonols intake and reduced risk of CHD (summary RR: 0.91; 95% CI: 0.83, 1.01). Furthermore, no significant association was found through the dose-response analysis (an increment of 20mg/day, summary RR: 0.96; 95% CI: 0.90, 1.03). CONCLUSIONS Our results do not support a protective role of flavonols intake against CHD.