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An association between gene expression and better survival in female mice following myocardial infarction.

ABSTRACT: Following myocardial infarction, the prognosis for females is better than males. Estrogen is thought to be protective, but clinical trials with hormone replacement failed to show protection. Here, we sought to identify novel mechanisms that might explain this sex-based difference. By diverging from the traditional focus on sex hormones, we employed a conceptually novel approach to this question by using a non-biased approach to measure global changes in gene expression following infarction. We hypothesized that specific gene programs are initiated in the heart following infarction that might account for this sex-based difference. We induced small, medium, and large infarcts in male and female mice and measured changes in gene expression by microarray following infarction. Regardless of infarct size, survival was better in females, while mortality occurred 3-10 days following infarction in males. Two days following infarction, males developed significant ventricular dilation, the best predictor of mortality in humans. Three days following infarction, we measured gene expression by microarray, comparing male versus female and sham versus surgery/infarction. In general, our results indicate a higher relative level of gene induction in females versus males and identified programs for angiogenesis, extracellular matrix remodeling, and immune response. This pattern of gene expression was linked to less pathologic remodeling in female hearts, including increased capillary density and decreased fibrosis. In summary, our results suggest an association between improved survival and less pathologic remodeling and the relative induction of gene expression in females following myocardial infarction.

SUBMITTER: Chen Q

PROVIDER: S-EPMC2956187 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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An association between gene expression and better survival in female mice following myocardial infarction.

Chen Quanhai Q Williams Roy R Healy Chastity L CL Wright Casey D CD Wu Steven C SC O'Connell Timothy D TD

Journal of molecular and cellular cardiology 20100806 5

Following myocardial infarction, the prognosis for females is better than males. Estrogen is thought to be protective, but clinical trials with hormone replacement failed to show protection. Here, we sought to identify novel mechanisms that might explain this sex-based difference. By diverging from the traditional focus on sex hormones, we employed a conceptually novel approach to this question by using a non-biased approach to measure global changes in gene expression following infarction. We h ...[more]

PMID: 20692266

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Project description:Background Whether the effect of smoking on clinical outcomes following an acute myocardial infarction (AMI) is beneficial or detrimental remains inconclusive. We invesetigated the effect of smoking on the clinical outcomes in patients following an AMI. Methods Among 13,104 patients between November 2011 and June 2015 from a nationwide Korean AMI registry, a total of 10,193 participants were extracted then classified into two groups according to their smoking habit: (1) smoking group (n = 6,261) and (2) non-smoking group (n = 3,932). The participants who smoked were further subclassified according to their smoking intensity quantified by pack years (PYs): (1) <20 PYs (n = 1,695); (2) 20–40 PYs (n = 3,018); and (3) ≥40 PYs (n = 2,048). Each group was compared to each other according to treatment outcomes. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCEs), which is a composite of all-cause mortality, non-fatal MI (NFMI), any revascularization, cerebrovascular accident, rehospitalization, and stent thrombosis. Secondary outcomes included the individual components of MACCEs. The Cox proportional hazard regression method was used to evaluate associations between baseline smoking and clinical outcomes following an AMI. Two propensity score weighting methods were performed to adjust for confounders, including propensity score matching and inverse probability of treatment weighting. Results While the incidence of all clinical outcomes, except for stent thrombosis, was lower in the smoking group than in the non-smoking group in the unadjusted data, the covariates-adjusted data showed statistical attenuation of these differences but a higher all-cause mortality in the smoking group. For smokers, the incidence of MACCEs, all-cause mortality, cardiac and non-cardiac death, and rehospitalization was significantly different between the groups, with the highest rates of MACCE, all-cause mortality, non-cardiac death, and rehospitalization in the group with the highest smoking intensity. These differences were statistically attenuated in the covariates-adjusted data, except for MACCEs, all-cause mortality, and non-cardiac death, which had the highest incidence in the group with ≥40 PYs. Conclusion Smoking had no beneficial effect on the clinical outcomes following an AMI. Moreover, for those who smoked, clinical outcomes tended to deteriorate as smoking intensity increased.

Project description:BackgroundPreclinical 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.Methods and resultsOverall, 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.ConclusionsThe 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.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.

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An association between gene expression and better survival in female mice following myocardial infarction.

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An association between gene expression and better survival in female mice following myocardial infarction.

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