The Study Of Relationship Between AMP-activated Protein Kinase Expression In Monocytes And Vulnerability Of Coronary Atherosclerotic Plaques

BackgroundAtherosclerosis is a chronic inflammatory disease that arises from vascular endothelial injury and coronary atherosclerotic plaque formation driven by macrophage infiltration. The pathophysiology of ACS is characterized by the formation of occlusive thrombi or nonocclusive thrombi in the coronary arteries. The rupture of plaque due to acute inflammation leads to coronary thrombosis, which is the common cause of ACS. Studies showed that monocytes/macrophages are the key cells associated with the vulnerability of atherosclerotic plaques. Monocytes are primary source of inflammatory effectors that may be more prone to contribute to atherosclerosis. Autophagy referred to as self-eating is a unique phenomenon in the eukaryocytes. Early investigations suggested that autophagy plays a positive function of coronary atherosclerotic disease. Autophagy of PBMs participates in the pathogenesis of plaque vulnerability and the subsequent plaque rupture. AMP-activated protein kinase (AMPK) as a sensor of cellular energy status can modulate glucolipid metabolism as switching from glycolysis to oxidative metabolism when glucose deprivation. Studies showed that autophagy may be induced via activation of AMPK and inhibition of mTOR in isolated cardiac myocytes. The up-regulation of AMPK promotes autophagy through a pathway involving the tuberous sclerosis complex (TSC1/2) and Rheb. However, Monocytes and macrophages contribute to the progression of atherosclerosis. However, research on the relationship among AMP-activated protein kinase (AMPK) and vulnerable atherosclerotic plaques is still insufficient.ObjectsWe aimed to elucidate the adaptive mechanism betweenautophagy of peripheral blood monocytes (PBMs) and therupture of atherosclerotic plaques. We investigated whether AMPK and autophagy of monocytes can enhance thestability of coronary atherosclerotic plaques in the humanbody.MethodsSamples of PBMs were collected and isolated from allpatients with stable angina pectoris (SAP), non-ST-segment elevation acute coronary syndrome, ST-segment elevation acute myocardial infarction, and without coronary artery disease (control). Then, western blot was used to detect theexpression levels of AMPK, p-AMPK, mTOR, p-mTOR and autophagy-related protein ATG-7, beclin-1.ResultsThe expression levels of beclin-1 and ATG7 were all significantly lower in the ACS groups thanthose in the SAP and control groups (all P<0.01). The level of phosphorylated AMPK was significantly decreased inpatients with ACS compared with those in the SAP andcontrol groups (P<0.01). However, there was no statistical difference between the SAP group and control group. The activation of mTOR was distinctly increased in the STEMI group(P<0.05).ConclusionsTherefore, our work is novel in showing that AMPK of PBMs may decrease plaque vulnerability and subsequent plaque rupture through activation of autophagy. Agents activating AMPK may provide a new target for the treatment of coronary heart disease (CHD).