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Erschienen in: Cardiovascular Drugs and Therapy 1/2013

01.02.2013 | ORIGINAL ARTICLE

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

verfasst von: Hannah J. Whittington, Andrew R. Hall, Catarina P. McLaughlin, Derek J. Hausenloy, Derek M. Yellon, Mihaela M. Mocanu

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 1/2013

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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.
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Metadaten
Titel
Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon
verfasst von
Hannah J. Whittington
Andrew R. Hall
Catarina P. McLaughlin
Derek J. Hausenloy
Derek M. Yellon
Mihaela M. Mocanu
Publikationsdatum
01.02.2013
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 1/2013
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-012-6425-x

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