Age-related differences in postinfarct left ventricular rupture and remodeling.
Cardiac rupture is more prevalent in elderly patients with first onset of acute myocardial infarct (MI), but the mechanism remains unexplored. We investigated the differences in the incidence of cardiac rupture and early left ventricular (LV) remodeling following coronary artery ligation between old (12-mo) and young (3-mo) C57Bl/6 male mice and explored responsible mechanisms. The incidence of rupture within 1 wk after MI was significantly higher in old than in young mice (40.7 vs. 18.3%, P = 0.013) despite a similar infarct size in both age groups. Old mice dying of rupture had more severe infarct expansion than young counterparts. Echocardiography and catheterization at day 7 revealed more profound LV chamber dilatation and dysfunction as well as higher blood pressures in aged mice. At day 3 after MI immediately before the peak of rupture occurrence, we observed significantly higher content of type I and III collagen, a greater density of macrophage and neutrophil, and markedly enhanced mRNA expression of inflammatory cytokines in the infarcted myocardium in old than in young mice. Furthermore, a more dramatic increment of matrix metalloproteinase (MMP)-9 activity was found in old than in young infarcted hearts, in keeping with enhanced inflammatory response. Collectively, these results revealed that old mice had a higher risk of post-MI cardiac rupture despite a higher level of collagen content and cross-linking. Enhanced inflammatory response and subsequent increase in MMP-9 activity together with higher blood pressure are important factors responsible for the higher risk of cardiac rupture and more severe LV remodeling in the aged heart following acute MI.
Yang
Yining
Y
Cardiovascular Research Institute, Xinjiang Medical University, Xinjinag, China.
Ma
Yitong
Y
Han
Wei
W
Li
Jun
J
Xiang
Yang
Y
Liu
Fen
F
Ma
Xiang
X
Zhang
Jianfa
J
Fu
Zhenyan
Z
Su
Yi-Dan
YD
Du
Xiao-Jun
XJ
Gao
Xiao-Ming
XM
D000367:Age Factors; D000818:Animals; D001794:Blood Pressure; D006328:Cardiac Catheterization; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003331:Coronary Vessels / Q000601:surgery; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D004789:Enzyme Activation; D006342:Heart Rupture, Post-Infarction / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008026:Ligation; D008264:Macrophages / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D020257:Ventricular Remodeling
D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse