TY - JOUR
T1 - Phagocyte-myocyte interactions and consequences during hypoxic wound healing
AU - Zhang, Shuang
AU - Dehn, Shirley
AU - DeBerge, Matthew
AU - Rhee, Ki Jong
AU - Hudson, Barry
AU - Thorp, Edward B.
N1 - Funding Information:
Funding from NIH 4R00HL097021-03 Grant from the NHLBI (to E.T.).
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing.
AB - Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing.
KW - Cardiomyocyte
KW - Monocyte
KW - Myocardial infarction
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U2 - 10.1016/j.cellimm.2014.04.006
DO - 10.1016/j.cellimm.2014.04.006
M3 - Article
C2 - 24862542
AN - SCOPUS:84908513897
VL - 291
SP - 65
EP - 73
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 1-2
ER -