fibrin and Coronary-Occlusion

Membrane-associated fibrinogen-like protein 2 (FGL2 prothrombinase, pFGL2) is abundantly expressed in activated microvascular endothelial cells (MVECs) and plays a crucial role in microthrombus formation in microcirculatory vasculature. It has been widely reported that coronary microvascular obstruction (CMVO) contributes to adverse outcomes following myocardial ischemia/reperfusion. However, the role of pFGL2 in CMVO is poorly understood.. We aimed to identify the effect of MVECs-pFGL2 in CMVO using FGL2 knockout mice. As results, the MVECs-pFGL2 expression progresses significantly over 3 days and then gradually decreases, which is positively correlated with the extent of CMVO as detected by HE staining in wild type mice. Furthermore, FGL2 deficiency is correlated with decreased areas of no-reflow and necrosis as detected by Evans Blue and TTC staining and that it ameliorates cardiac dysfunction detected by hemodynamics in the early stage of CMVO. Moreover, fibrin deposition in microvasculature is significantly reduced in FGL2-deficient mice as evidenced by immunohistochemistry, MSB and Carstairs staining, along with the down-regulation of leukocyte adhesion and infiltration. Additionally, we observed that the FGL2 deficiency decreases macrophage infiltration and shifts the macrophage phenotype from pro-inflammatory (M1,) to anti-inflammatory (M2,) pattern in the early stage of CMVO.. These findings highlight the MVECs-pFGL2-fibrin pathway in the early stage of CMVO and provide insights into coagulation and inflammation for the coronary artery disease therapeutics.

Topics: Animals; Blood Coagulation; Blotting, Western; Coronary Circulation; Coronary Occlusion; Coronary Vessels; Disease Models, Animal; Endothelium, Vascular; Fibrin; Fibrinogen; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Microcirculation; Time Factors

There are few histologic studies of intracoronary stents found at autopsy. We studied histologic findings of 87 intracoronary stents from 45 autopsy hearts. There were 40 patients with chronically implanted stents and five shorter than 30 days. Of five patients with recent stent placement, the cause of death was related to the stent (in-stent thrombosis) in one case. Of the 40 patients with chronic stents, there were 16 sudden coronary deaths and 24 noncoronary deaths (controls). There were no late stent thromboses in the coronary deaths. In the coronary deaths, 26% of stents showed restenosis versus 11% in controls (p = 0.1). The rate of healed infarcts and cardiomegaly was similar in the coronary and noncoronary groups, and acute thrombi in native arteries were seen only in three hearts in the coronary group. We conclude that the cause of death is rarely impacted by in-stent findings at autopsy, especially in chronically implanted stents.

Topics: Cardiomegaly; Case-Control Studies; Coronary Occlusion; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Death, Sudden, Cardiac; Female; Fibrin; Forensic Pathology; Giant Cells; Humans; Male; Middle Aged; Myocardial Infarction; Myocardium; Neointima; Prospective Studies; Stents

Topics: Castration; Coronary Disease; Coronary Occlusion; Eating; Fats; Fibrin; Hormones; Humans; Lipid Metabolism; Lipids; Sex Characteristics