Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
نویسندگان
چکیده
Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chigh) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6Clow Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signalling and subsequently inhibits Ly6Clow Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE2/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6Clow Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.
منابع مشابه
Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1.
Niacin is a well established drug used to lower cholesterol and prevent cardiovascular disease events. However, niacin also causes cutaneous flushing side effects due to release of the proresolution mediator prostaglandin D2 (PGD2). Recent randomized clinical trials have demonstrated that addition of niacin with laropiprant [a PGD2 receptor subtype 1 (DP1) blocker] to statin-based therapies doe...
متن کاملDectin-2 Deficiency Modulates Th1 Differentiation and Improves Wound Healing After Myocardial Infarction.
RATIONALE Macrophages are involved in wound healing after myocardial infarction (MI). The role of Dectin-2, a pattern recognition receptor mainly expressed on myeloid cells, in the infarct healing remains unknown. OBJECTIVE The aim of this study is to determine whether Dectin-2 signaling is involved in the healing process and cardiac remodeling after MI and to elucidate the underlying molecul...
متن کاملThe Effect of Eight Weeks of Intermittent Training with Quercetin Encapsulated Nanoparticles on JNK and ERK Apoptosis Regulators in the Rat Model of Myocardial Infarction
Introduction: Restoration of blood flow to the ischemic heart muscle causes infarction and myocyte death. Quercetin can be effective in treating heart disease due to its antioxidant effect, but its use is limited due to its low solubility in water. Quercetin restriction can be removed by embedding it in carrier nanoparticles. The present study was designed to determine the effect of quercetin e...
متن کاملEffects of Doxycycline on Cx43 Distribution and Cardiac Arrhythmia Susceptibility of Rats after Myocardial Infarction
Effects of Doxycycline on Cx43 Distribution and Cardiac Arrhythmia Susceptibility of Rats after Myocardial Infarction Abstract: This study aimed to observe the effects of doxycycline (DOX) on gap junction remodeling after MI and the susceptibility of rats to cardiac arrhythmia. The proximal left anterior descending coronary artery of rats was ligated to establish a myocardial infarction animal...
متن کاملPrediction of long-term cardiac events by 123I-MIBG imaging after acute myocardial infarction and reperfusion therapy
Objective(s): In heart failure, the heart-to-mediastinum (H/M) ratio of the delayed image and washout rate (WR) are well-known as a powerful cardiac event predictors. H/M ratio quantifies the accumulation rate of MIBG in the myocardium and WR quantifies reduction of meta-iodobenzylguanidine (MIBG) accumulation in the heart from the early planar image to the delayed pla...
متن کامل