Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of trimetazidine, an anti-ischaemic agent, has been largely assessed and presented in the international literature through its metabolic effects, selective and specific fatty acid oxidation inhibition and lack of haemodynamic effects in stable angina pectoris. As such, trimetazidine has opened up a new class of metabolic agents that reduce fatty acid oxidation: the 3-KAT (3-ketoacyl-CoA thiolase) inhibitors. The aim of this review article is to demonstrate the cardioprotective benefits of trimetazidine, and how this can be translated into positive effects in the treatment of cardiac disorders. Trimetazidine has been assessed in several double-blind randomised studies as a treatment of ischaemic heart disease or as an agent given prior to or during percutaneous transluminal coronary angioplasty, coronary artery bypass grafting and thrombolysis to prevent or limit ischaemia/reperfusion damage in the heart. All these studies demonstrate that trimetazidine protects the heart from the deleterious consequences of ischaemia by switching cardiac metabolism from fatty acid oxidation to glucose oxidation. Study results cast no doubts on the value of the cardioprotective effects of trimetazidine and support the fact that trimetazidine has a direct anti-ischaemic effect on human myocardial cells. Trimetazidine has proven antianginal efficacy, and can be also used in other cardiac diseases with ischaemic signs.
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PMID:Cardioprotective effects of trimetazidine: a review. 1460 90

There is a growing need to understand the underlying mechanisms involved in the progression of cardiovascular disease during obesity and diabetes. Although inhibition of fatty acid oxidation has been proposed as a novel approach to treat ischemic heart disease and heart failure, reduced muscle fatty acid oxidation rates may contribute to the development of obesity-associated insulin resistance. Our aim was to determine whether treatment with the antianginal agent trimetazidine, which inhibits fatty acid oxidation in the heart secondary to inhibition of 3-ketoacyl-CoA thiolase (3-KAT), may have off-target effects on glycemic control in obesity. We fed C57BL/6NCrl mice a high-fat diet (HFD) for 10 weeks before a 22-day treatment with the 3-KAT inhibitor trimetazidine (15 mg/kg per day). Insulin resistance was assessed via glucose/insulin tolerance testing, and lipid metabolite content was assessed in gastrocnemius muscle. Trimetazidine-treatment led to a mild shift in substrate preference toward carbohydrates as an oxidative fuel source in obese mice, evidenced by an increase in the respiratory exchange ratio. This shift in metabolism was accompanied by an accumulation of long-chain acyl-CoA and a trend to an increase in triacylglycerol content in gastrocnemius muscle, but did not exacerbate HFD-induced insulin resistance compared with control-treated mice. It is noteworthy that trimetazidine treatment reduced palmitate oxidation rates in the isolated working mouse heart and neonatal cardiomyocytes but not C2C12 skeletal myotubes. Our findings demonstrate that trimetazidine therapy does not adversely affect HFD-induced insulin resistance, suggesting that treatment with trimetazidine would not worsen glycemic control in obese patients with angina.
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PMID:Treatment with the 3-ketoacyl-CoA thiolase inhibitor trimetazidine does not exacerbate whole-body insulin resistance in obese mice. 2470 Aug 85