Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial DNA 5178 C/A (mt5178 C/A), namely NADH dehydrogenase subunit 2 237 Leu/Met, polymorphism is as reported in literature associated with longevity and susceptibility to ischemic heart disease or cerebrovascular disorders in the Japanese population. Previous reports suggested that mt5178A genotype exerts antiatherogenic effects. The aim of this study was to investigate whether mt5178 C/A polymorphism is associated with hematological parameters, such as thrombogenic risk factors for myocardial infarction and stroke, in 321 healthy Japanese men. No significant differences were observed between mt5178 C/A genotypes, but in subjects with body mass index (BMI) of < or = 23, this polymorphism influenced the effects of habitual smoking on hematological parameters. Red blood cell (RBC) counts were significantly lower and mean corpuscular hemoglobin (MCH) levels were significantly higher in smokers with mt5178A than nonsmokers with mt5178A. Platelet counts were significantly higher in smokers with mt5178C than nonsmokers with mt5178C. Cigarette consumption was strongly associated with RBC counts, mean corpuscular volume levels, and MCH levels for men with mt5178A, and was associated with platelet counts for those with mt5178C. Moreover, BMI was significantly positively associated with RBC counts and platelet counts only in men with mt5178A, age was significantly negatively associated with RBC counts only in men with mt5178C. These data suggest that mt5178 C/A polymorphism may influence the effects of cigarette smoking on hematological parameters in healthy BMI < or = 23 Japanese men.
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PMID:Interaction between longevity-associated mitochondrial DNA 5178 C/A polymorphism and cigarette smoking on hematological parameters in Japanese men. 1568 Apr 95

Mitochondrial dysfunction plays a major role in the pathogenesis of cardiovascular diseases. MicroRNAs (miRNAs) are small RNAs that act as negative regulators of gene expression, but how miRNAs affect mitochondrial function in the heart is unclear. Using a miRNA microarray assay, we found that miR-762 predominantly translocated in the mitochondria and was significantly upregulated upon anoxia/reoxygenation (A/R) treatment. Knockdown of endogenous miR-762 significantly attenuated the decrease in intracellular ATP levels, the increase in ROS levels, the decrease in mitochondrial complex I enzyme activity and the increase in apoptotic cell death in cardiomyocytes, which was induced by A/R treatment. In addition, knockdown of miR-762 ameliorated myocardial ischemia/reperfusion (I/R) injury in mice. Mechanistically, we showed that enforced expression of miR-762 dramatically decreased the protein levels of endogenous NADH dehydrogenase subunit 2 (ND2) but had no effect on the transcript levels of ND2. The luciferase reporter assay showed that miR-762 bound to the coding sequence of ND2. In addition, knockdown of endogenous ND2 significantly decreased intracellular ATP levels, increased ROS levels, reduced mitochondrial complex I enzyme activity and increased apoptotic cell death in cardiomyocytes, which was induced by A/R treatment. Furthermore, we found that the inhibitory effect of miR-762 downregulation was attenuated by ND2 knockdown. Thus, our findings suggest that miR-762 participates in the regulation of mitochondrial function and cardiomyocyte apoptosis by ND2, a core assembly subunit of mitochondrial complex I. Our results revealed that mitochondrial miR-762, as a new player in mitochondrial dysfunction, may provide a new therapeutic target for myocardial infarction.
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PMID:Mitochondrial miR-762 regulates apoptosis and myocardial infarction by impairing ND2. 3123 86