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The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPAR? Pathway.

ABSTRACT: Aim: Danqi Pill (DQP), a Chinese medicine frequently prescribed in China, has been approved to improve cardiac function by regulating cardiac energy metabolism in heart failure (HF) after acute myocardial infarction (AMI) patients. The aim of this study was to explore whether the mechanism of DQP is associated to the lipid and glucose metabolism mediated via PPAR? (peroxisome proliferator-activated receptor gamma) pathway both in vivo and in vitro. Materials and Methods: Model of HF after AMI was established with ligation of left anterior descending artery on Sprague-Dawley (SD) rats. Twenty-eight days after treatment, hematoxylin-eosin (HE) staining was applied to visualize cardiomyocyte morphological changes. High performance liquid chromatography (HPLC) was performed to assess the contents of adenosine phosphates in heart. Positron emission tomography and computed tomography (PET-CT) was conducted to evaluate the cardiac glucose metabolism. Expressions of key molecules such as PPAR?, sterol carrier protein 2 (SCP2) and long chain acyl CoA dehydrogenase (ACADL) were measured by Western blotting (WB) and immunohistochemistry (IHC). Oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro. Results: Treatment with DQP rescued hearts from structural and functional damages as well as inflammatory infiltration. Levels of adenosine triphosphate (ATP) and energy charge (EC) in DQP group were also up-regulated compared to model group. Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compromised in model group compared to sham group. Intriguingly, DQP could up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously. Results on upstreaming signaling pathway demonstrated that DQP could dramatically increase the expressions of PPAR?. In vitro study suggested the efficacy of DQP could be blocked by T0070907, a selective PPAR? inhibitor. Conclusion: DQP has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism. The effects may be mediated by PPAR? pathway.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6207917 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPARγ Pathway.

Zhang Qian Q Shao Mingyan M Zhang Xuefeng X Wang Qiyan Q Guo Dongqing D Yang Xiaomin X Li Chun C Wang Yong Y

Frontiers in pharmacology 20181024

Aim: Danqi Pill (DQP), a Chinese medicine frequently prescribed in China, has been approved to improve cardiac function by regulating cardiac energy metabolism in heart failure (HF) after acute myocardial infarction (AMI) patients. The aim of this study was to explore whether the mechanism of DQP is associated to the lipid and glucose metabolism mediated via PPARγ (peroxisome proliferator-activated receptor gamma) pathway both in vivo and in vitro. Materials and Me ...[more]

PMID: 30405421

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Project description:BackgroundOral antiplatelet therapy is the cornerstone of treatment for acute myocardial infaction (AMI). However, detailed usage data on oral antiplatelet therapy are lacking.MethodsUsing data from a nationally representative sample of patients with AMI, the detailed usage of oral antiplatelet therapy was analyzed in 40,202 consecutive eligible patients.ResultsThe proportions of patients with AMI taking loading doses of aspirin and P2Y12 inhibitors were relatively low (62.2% and 63.6%, respectively), whereas approximately 90% of patients received maintenance doses of aspirin, P2Y12 inhibitors, and dual antiplatelet therapy. The proportions of patients taking loading doses of aspirin and P2Y12 inhibitors gradually decreased with age. Male sex, an educational level of at least college, an interval from onset to treatment of < 24 h, and primary PCI use were associated with a higher proportion of patients taking a loading dose of antiplatelet therapy, whereas those receiving conservative treatment had a lower rate of antiplatelet use (all P < 0.05). The proportion of patients taking loading doses of aspirin was highest in the western region, and that of patients taking loading doses of P2Y12 inhibitors was highest in the eastern region (P < 0.05). In addition, 76.7% of patients with ST-elevation MI and 91% of patients with non-ST-elevation MI received 300-mg loading dose of clopidogrel.ConclusionsThe proportion of patients with AMI receiving loading doses of aspirin and P2Y12 inhibitors during hospitalization was relatively low, and this rate was affected by many factors, such as age, sex, educational level, region of residence, and the interval from onset to treatment. The underutilization of guideline-based P2Y12 inhibitors was also problematic. Hence, quality improvement initiatives are needed to enhance adherence to guidelines to improve consistent use of oral antiplatelet therapy. Trial registration The Chinese Acute Myocardial Infarction Registry; Trial registration number: ChiCTR-ONC-12002636; Registered 31 October 2012; http://www.chictr.org.cn/showproj.aspx?proj=6916.

Project description:Objectives: We intend to conduct a meta-analysis on the systematic evaluation of traditional Chinese medicine (TCM) in the treatment of ventricular remodeling following acute myocardial infarction (AMI). Our findings may provide certain references for the clinical treatment of ventricular remodeling. Methods: A systematic literature search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang Data, CQVIP, and CBM before 20 July 2020. Data were analyzed using a random/fixed-effect model. Primary outcomes included the effectiveness and TCM syndrome score (TCMSS). Secondary outcomes included 1) echocardiography data, including the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (LVEF), E/A, stroke volume (SV), and wall motion score (WMS); 2) serum indicators, including the B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) or high sensitivity CRP (hs-CRP); (3) major adverse cardiovascular events (MACE) and other adverse events Results: Forty RCTs involving 3,659 subjects were recruited. Our findings proved that a combination of TCM or TCM preparations with conventional Western medicine for preventing and reversing ventricular remodeling at post-AMI could remarkably enhance the total effectiveness and reduced TCMSS. Moreover, myocardial functions (LVEF, E/A, and SV), ventricular remodeling (LVEDVi, LVESVi, LVEDV, LVESV, LVEDD, LVESD, LVPWT, and WMS), serum levels of BNP and CRP, and MACE were significantly improved by the combination of TCM or TCM preparations with conventional Western medicine. Nevertheless, IVST and the incidence of other adverse events were comparable between control and experimental groups Conclusion: The combination of TCM or TCM preparations and conventional Western medicine can alleviate the process of ventricular remodeling, enhance cardiac function, and reduce the incidence of MACE in AMI patients.

Project description:Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (?30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

Project description:BackgroundThe prognostic effect of admission blood glucose (ABG) for patients with acute myocardial infarction (AMI) has not been well validated, especially in patients with diabetes. We performed this study to assess the predictive value of ABG for all-cause mortality in AMI patients with different glucose metabolism status.MethodsWe evaluated a total of 6,892 AMI patients from the prospective, nationwide, multicenter CAMI registry, of which 2,820 had diabetes, 2,011 had pre-diabetes, and 2,061 had normal glucose regulation (NGR). Patients were divided into high ABG and low ABG groups according to the optimal cutoff values of ABG to predict 2-year mortality for patients with diabetes, pre-diabetes and NGR, respectively. The primary endpoint was all-cause mortality.ResultsThe optimal cutoff values of ABG for predicting 2-year mortality was 9.0mmol/l, 7.2mmol/l and 6.2mmol/l for patients with diabetes, pre-diabetes and NGR, respectively. Overall, the risk of all-cause mortality in high ABG group was significantly increased compared with that in low ABG group among patients with diabetes (15.2% vs. 8.9%; hazard ratio [HR] 1.787, 95% confidence interval [CI] 1.413-2.260; P<0.0001), pre-diabetes (12.1% vs. 6.1%; HR 2.069, 95%CI 1.518-2.821; P<0.0001) and NGR (11.8% vs. 6.1%; HR 2.009, 95%CI 1.473-2.740; P<0.0001). After the potential confounders were adjusted, high ABG was significantly associated with higher risk of 2-year mortality in patients with diabetes (adjusted HR 1.710, 95%CI 1.327-2.203; P<0.0001), pre-diabetes (adjusted HR 1.731, 95%CI 1.249-2.399; P=0.001) and NGR (adjusted HR 1.529, 95%CI 1.110-2.106; P=0.009). Moreover, adding ABG to the original model led to a slight albeit significant improvement in C-statistic and net reclassification in patients with diabetes and NGR (all P<0.05).ConclusionsThis study is the first to demonstrate a strong positive association between ABG and 2-year mortality in AMI patients with diabetes, pre-diabetes and NGR. ABG should be considered as a useful marker for risk stratification in patients with diabetes and NGR. Further randomized trials are warranted to investigate the effects of blood glucose control on the reduction of long-term mortality according to the corresponding ABG thresholds for different glucose metabolism status.Clinical trial registrationClinicalTrials.gov, identifier NCT01874691.

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The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPAR? Pathway.

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The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPARγ Pathway.

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