By Joe Boyle
In a paper just published in Cardiovascular Research, we have shown that the oral antidiabetic drug metformin may suppress atherosclerotic lesion development in mice. This was done at level similar to those found in diabetic patients, in whom the effect was suspected to occur but presumed to be via blood glucose reduction. We have shown that metformin is strongly atheroprotective in mice, but this is not mediated by blood glucose reduction.
Instead, it is mediated via the regulatory enzyme adenosine monophosphate activated protein kinase (AMPK) in leukocytes, in which it has an anti-inflammatory effect. The anti-inflammatory effect was mediated by Activating Transcription Factor 1 (ATF1), which induced key atheroprotective genes in response to metformin. Regulation of genes in plaque macrophages in vivo was similar to that in cultured human and mouse macrophages. This work indicates that the atheroprotective effects of metformin may be directly on plaque macrophages rather than via hypoglycemia. The logical next step would be a clinical trial of metformin in non-diabetic patients at high vascular risk.
Link to publication: https://pubmed.ncbi.nlm.nih.gov/32667970/
References
Seneviratne A, Cave L, Hyde G, Moestrup SK, Carling D, Mason JC, Haskard DO, Boyle JJ (2020) Metformin directly suppresses atherosclerosis in normoglycemic mice via haematopoietic Adenosine Monophosphate-Activated Protein Kinase (AMPK). Cardiovasc Res. 2020 July 15
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