Metformin's Potential Role in Atherosclerosis Explored

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Metformin's Potential Role in Atherosclerosis Explored
Metformin's Potential Role in Atherosclerosis Explored

(HealthDay News) — Metformin's role in atherosclerosis may be inhibition of monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation, according to research published online Dec. 31 in Diabetes.

Sathish Babu Vasamsetti, from the Indian Institute of Chemical Technology in Hyderabad, and colleagues examined the molecular mechanisms responsible for monocyte-to-macrophage differentiation. They also examined the effect of metformin in regressing Angiotensin-II-mediated atheromatous plaque formation in ApoE−/− mice.

The researchers observed a dose- and time-dependent downregulation in AMPK activity during PMA-induced monocyte-to-macrophage differentiation; this was accompanied by upregulation of production of pro-inflammatory cytokines. These were significantly attenuated with AMPK activators metformin and AICAR. In the absence of PMA, compound C-induced inhibition of AMPK activity alone was not effective for promoting monocyte-to-macrophage differentiation. JNK activity inhibited the inflammation induced by PMA, but not differentiation. Both inflammation and monocyte-to-macrophage differentiation were inhibited with inhibition of STAT3 activity. Increased AMPK activation with metformin and AICAR decreased STAT3 phosphorylation, causing inhibition of the differentiation of monocytes to macrophages. In ApoE−/− mice, metformin attenuated Ang-II-induced atheromatous plaque formation and aortic aneurysm, partly by decreasing infiltration of monocytes.

"We conclude that AMPK-STAT3 axis plays a pivotal role in regulating monocyte-to-macrophage differentiation and that AMPK activators by decreasing STAT3 phosphorylation through increased AMPK activity inhibit monocyte-to-macrophage differentiation," the authors write.

Abstract
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