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Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon

Whittington, HJ; Hall, AR; McLaughlin, CP; Hausenloy, DJ; Yellon, DM; Mocanu, MM; (2013) Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon. Cardiovascular Drugs and Therapy , 27 (1) pp. 5-16. 10.1007/s10557-012-6425-x. Green open access

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Abstract

Purpose: Clinical and experimental investigations demonstrated that metformin, a widely used anti-diabetic drug, exhibits cardioprotective properties against myocardial infarction. Interestingly, metformin was previously shown to increase the expression of PGC-1α a key controller of energy metabolism in skeletal muscle, which is down-regulated in diabetic conditions. We hypothesized that chronic treatment with metformin could protect the aged, diabetic heart against ischemia-reperfusion injury (IRI) by up-regulating PGC-1α and improving the impaired functionality of diabetic mitochondria. / Methods: Following 4 weeks of metformin (300 mg/kg) administered in the drinking water, 12 month-old diabetic Goto Kakizaki and non-diabetic Wistar rat hearts were assigned for infarct measurement following 35 min ischemia and 60 min reperfusion or for electron microscopy (EM) and Western blotting (WB) investigations. / Results: Metformin elicited a cardioprotective effect in both non-diabetic and diabetic hearts. In contrast with the diabetic non-treated hearts, the diabetic hearts treated with metformin showed more organized and elongated mitochondria and demonstrated a significant increase in phosphorylated AMPK and in PGC-1α expression. / Conclusions: In summary these results show for the first time that chronic metformin treatment augments myocardial resistance to ischemia-reperfusion injury, by an alternative mechanism in addition to the lowering of blood glucose. This consisted of a positive effect on mitochondrial structure possibly via a pathway involving AMPK activation and PGC-1α. Thus, metformin prescribed chronically to patients may lead to a basal state of cardioprotection thereby potentially limiting the occurrence of myocardial damage by cardiovascular events.

Type: Article
Title: Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10557-012-6425-x
Publisher version: http://dx.doi.org/10.1007/s10557-012-6425-x
Language: English
Additional information: The final publication is available at Springer via http://dx.doi.org/10.1007/s10557-012-6425-x.
Keywords: Ischemia–reperfusion injury, Cardioprotection, PGC-1α, Metformin
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Hatter Cardiovascular Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/1378727
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