The Study Of Relationship Between Autophagy Related Proteins Expression In Monocytes And Vulnerability Of Coronary Atherosclerotic Plaques

BackgroundNumerous studies have indicated that thrombosis secondary to the rupture of vulnerable atherosclerotic plaque is the major cause of acute coronary syndrome (ACS). Autopsies performed on patients with ACS indicates that a large number of macrophages, lymphocytes and mast cells exist in the coronary atherosclerotic plaques. To be more precisely, macrophages are the main components of all the cells in the vulnerable plaques. The more macrophages infiltrate in the fibrous cap, the more vulnerable plaque will be, which results from the matrix metalloproteinases (MMPs) secreted by macrophages that can degrade extracellular matrix leading to the thinning of the fibrous cap. Simultaneously, considerable cytokines such as IL-1、 IL-8、TNFa and various adhesion molecules such as ICAM-1、VCAM-land P-selectin secreted by macrophages promote the plaque to transform into an unstable one. Therefore, an intensive study of functions of peripheral blood monocytes (PBMs) from which macrophages are derived has important significance to understand pathophysiology of ACSAutophagy is a unique and ubiquitous phenomenon in the eukaryocytes, which is defined as a major protein degradation process responsible for the degradation of unnecessary or dysfunctional cellular components via the lysosomal machinery. A great many studies have indicated that autophagy is closely involved in the changes of cells in the atherosclerotic plaques. So, the aim of our study is to elucidate the relationship between autophagy of peripheral blood monocyte (PBM) and the vulnerability of atherosclerotic plaques, furthermore to find a new therapeutic target of stabilizing atherosclerotic plaques and reducing acute coronary events.At present, although coronary angiography (CAG) has been considered as "gold standard" to diagnose coronary heart disease(CHD). Given that it can only display the degree of coronary artery stenosis, there are also many limitations when to evaluate morphology and thickness of coronary wall and the stability of plaques. Intravascular unltrasound(IVUS) is a medical device that combine invasive catheter technology with a high frequency miniature ultrasonic probe. The ultrasound catheter is inserted into coronary artery to detect the lesions, thus it can not only precisely measure the diameter and cross-sectional area of coronary artery, what’s more, it can assess the stability of plaques, which can provide more information about the coronary artery lesions. Therefore IVUS has unparalleled advantages when compared with CAG.Objective1To elucidate the relationship between autophagy of peripheral blood monocyte (PBM) and the vulnerability of atherosclerotic plaques.2To discuss the intravascular ultrasonic features of coronary atherosclerotic plaques in stable angina and ACS patients MethodsForty patients with stable angina pectoris (SAP),40patients with acute coronary syndrome (ACS) compromised the study groups. All of patients underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) examinations. The expression levels of autophagy related protein Beclin-1, microtubule-associated protein1light chain3(MAP1-LC3) and ATG5-ATG12complex in PBM was detected by Western blot. MAP1-LC3(autophagy-specific protein) in the PMB was also examined by laser scanning confocal microscope.ResultsSixty two plaques were detected by IVUS in the SAP patients, which included30fibrous ones, while71plaques were evidenced in the ACS group, which encompassed40lipid ones. The expression levels of Beclin-1, MAP1-LC3and ATG5-ATG12complex in PBM in ACS patients were significantly lower than those in SAP patients (P<0.01).ConclusionThe patients in SAP group had more stable fibrous plaques than those in the ACS group (P<0.01), while the ACS patients had more vulnerable soft lipid ones than those in the SAP group (P<0.01). The autophagy of PBM in patients with coronary heart disease (CHD) decreases with the increasing vulnerability of atherosclerotic plaques. Enhancing the autophagy of PBM may be a potential therapeutic target of stabilizing atherosclerotic plaques, which will reduce the acute coronary events and lower the mortality of patients with CHD.