Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.
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PMID:A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. 2290 39

Despite decades of research, obesity and diabetes remain major health problems in the USA and worldwide. Among the many complications associated with diabetes is an increased risk of cardiovascular diseases, including myocardial infarction and heart failure. Recently, microRNAs have emerged as important players in heart disease and energy regulation. However, little work has investigated the role of microRNAs in cardiac energy regulation. Both human and animal studies have reported a significant increase in circulating free fatty acids and triacylglycerol, increased cardiac reliance on fatty acid oxidation, and subsequent decrease in glucose oxidation which all contributes to insulin resistance and lipotoxicity seen in obesity and diabetes. Importantly, MED13 was initially identified as a negative regulator of lipid accumulation in Drosophilia. Various metabolic genes were downregulated in MED13 transgenic heart, including sterol regulatory element-binding protein. Moreover, miR-33 and miR-122 have recently revealed as key regulators of lipid metabolism. In this review, we will focus on the role of microRNAs in regulation of cardiac and total body energy metabolism. We will also discuss the pharmacological and non-pharmacological interventions that target microRNAs for the treatment of obesity and diabetes.
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PMID:MicroRNAs 33, 122, and 208: a potential novel targets in the treatment of obesity, diabetes, and heart-related diseases. 2796 96

Diabetic cardiomyopathy refers to a unique set of heart-specific pathological variables induced by hyperglycemia and insulin resistance. Given that cardiovascular disease (CVD) is the leading cause of death in the world, and type 2 diabetes incidence continues to rise, understanding the complex interplay between these two morbidities and developing novel therapeutic strategies is vital. Two hallmark characteristics specific to diabetic cardiomyopathy are diastolic dysfunction and cardiac structural mal-adaptations, arising from cardiac cellular responses to the complex toxicity induced by hyperglycemia with or without hyperinsulinemia. While type 2 diabetes is more prevalent in men compared to women, cardiovascular risk is higher in diabetic women than in diabetic men, suggesting that diabetic women take a steeper path to cardiomyopathy and heart failure. Accumulating evidence from randomized clinical trials indicate that although pre-menopausal women have lower risk of CVDs, compared to age-matched men, this advantage is lost in diabetic pre-menopausal women, which suggests estrogen availability does not protect from increased cardiovascular risk. Notably, few human studies have assessed molecular and cellular mechanisms regarding similarities and differences in the progression of diabetic cardiomyopathy in men versus women. Additionally, most pre-clinical rodent studies fail to include female animals, leaving a void in available data to truly understand the impact of biological sex differences in diabetes-induced dysfunction of cardiovascular cells. Elegant reviews in the past have discussed in detail the roles of estrogen-mediated signaling in cardiovascular protection, sex differences associated with telomerase activity in the heart, and cardiac responses to exercise. In this review, we focus on the emerging cellular and molecular markers that define sex differences in diabetic cardiomyopathy based on the recent clinical and pre-clinical evidence. We also discuss miR-208a, MED13, and AT2R, which may provide new therapeutic targets with hopes to develop novel treatment paradigms to treat diabetic cardiomyopathy uniquely between men and women.
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PMID:Diabetic Cardiomyopathy: Impact of Biological Sex on Disease Development and Molecular Signatures. 2977 93