Pharmacological PTB1B Inhibition Reduces Atherosclerotic Plaque

We present evidence that, in addition to its improvement in glucose homeostasis and adiposity, PTP1B inhibition results in activation of aortic Akt and AMPKα1, that is independent of the effects on the IR itself. Most importantly, for the first time, we demonstrate that inhibition of PTP1B results in a decrease in circulating serum cholesterol and triglyceride levels and protection against atherosclerotic plaque formation. Atherosclerosis is now widely regarded as a chronic, low-grade inflammatory condition characterized by an increased pro-inflammatory environment and decreased anti-inflammation, pro-resolutionary signalling. Thus, a vicious cycle ensues and a failure of the tissue to return to homeostasis. Therefore, we investigated the expression of genes important in the inflammatory response including MCP-1, ICAM-1 and VCAM-1. MCP-1 is responsible for recruiting monocytes to the aortic tissue whereas both ICAM-1 and VCAM-1 enable their transmigration. Although there were no changes in the expression of aortic ICAM-1 or VCAM-1, those animals treated with a single injection of trodusquemine exhibited attenuated aortic MCP-1 expression levels. Hence, suggesting less monocyte recruitment and a reduced inflammatory environment which could contribute to the reduction in plaque development. Link: https://doi.org/10.1042/CS20171066
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