Survival of Cardiomyocytes in the Subendocardial Region in Response to Myocardial Ischemic Injury in Mice

Abstract

Ischemic injury results in the death of cardiomyocytes, impairing myocardial function and eventually leading to heart failure. However, it was observed that there are cardiomyocytes, located in subendocardial region, that are often survived from ischemic injury. The present study was to explore possible mechanisms for the survival of the cardiomyocytes in this particular subendocardial location. Male C57 mice (8–12 weeks old) were divided into sham-operated control and myocardial ischemia (MI) groups. Mice in the MI group were subjected to permanent ligation of left anterior descending (LAD) coronary artery. After 1, 4 or 7 days post surgery, mice were injected intravenously with either pimonidazole to define hypoxic regions or FITC labeled wheat germ agglutinins (WGA) to trace blood infiltration. One hour after the injection, the mice were euthanatized. The hearts were collected and then cut into serial frozen sections for further analyses including cell apoptosis, blood supply and hypoxic condition. The results showed that the survived cardiomyocytes located in the subendocardial region were adjacent to the wall of the left ventricle. The TUNEL staining showed that apoptotic cells were significantly increased in the ischemic area on the 1st day after LAD ligation, but a few apoptotic cells were identified in the subendocardial region. The staining of pimonidazole showed that most of the affected myocardium was under hypoxic condition except the subendocardial region, but the CD31 positive capillaries were all disappeared in the ischemic area including the subendocardial region. The WGA staining showed a complete occlusion of blood infiltration, but there was WGA leakage in the subendocardial region. Further analysis revealed that the tight junction of the endocardium defined by VE-cadherin immunostaining was disturbed, likely responsible for WGA leakage. These results thus suggest that the breakage of the tight junction of the endocardium would lead to blood infiltration from left ventricle, which might nurture the cardiomyocytes located in the subendocardial region, leading to their survival. Support or Funding Information Supported by scientific research funding of West China Hospital Sichuan University. Morphalogical changes of cardiomyocytes after ischemic injury Cell apoptosis, hypoxia and capillaries distribution in ischemic area Endothelial junction breakage and blood infiltration from left ventricle. Morphalogical changes of cardiomyocytes after ischemic injury Cell apoptosis, hypoxia and capillaries distribution in ischemic area Endothelial junction breakage and blood infiltration from left ventricle. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.