Dislocation of Lysyl Oxidase and Deformation of Cardiomyocytes in Response to Myocardial Ischemic Injury in Mice

Abstract

Lysyl oxidase (LOX), a copper‐dependent amine oxidase, is located in the intercalated discs between cardiomyocytes in the heart and responsible for the catalysis of collagen and elastin cross‐linking of the extracellular matrixes. However, in response to myocardial ischemic injury, LOX is dislocated to the cytosol, along with deformation, of cardiomyocytes in the ischemic myocardium. The present study was undertaken to explore the relationship between LOX dislocation and the deformation of cardiomyocytes in response to myocardial ischemia. Male C57BL/6J mice aged 8–12 weeks old were subjected to left anterior descending (LAD) coronary artery ligation to induce ischemic injury. The hearts were collected at 1st, 4th, or 7th day after the surgery and cut into frozen/paraffin sections to detect LOX location and the morphological changes of cardiomyocytes. Most of the survived cardiomyocytes in the ischemic infarct area were deformed from the rod‐shaped to the rounded detected on the 7th day after the surgery. Corresponding to the deformation of cardiomyocytes, the junction between cardiomyocytes become disturbed, and the intercalated discs disappeared. Connexin 43 (Cx43), an important gap junction protein located in the intercalated discs, was significantly reduced in the ischemic infarct area at day 1, but slightly recovered at day 7 after LAD ligation. However, the recovered Cx43 proteins were mainly located in the cytosol of cardiomyocytes. LOX proteins were increased gradually from day 1 to day 7 in the ischemic infarct area in comparison with the sham‐operated controls, and were mostly dislocated in the cytosol of cardiomyocytes. The results suggest that in response to ischemic injury, dislocation of LOX in cytosol of cardiomyocytes is likely responsible at least in part for the breakage of the junction between cardiomyocytes, leading to loss of the cell polarity and impaired contractile function of cardiomyocytes.Support or Funding InformationScientific research funds of West China Hospital, Sichuan UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.