Junctional adhesion molecule-A prevents cardiac rupture following myocardial infarction

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University of Delaware
Cardiovascular diseases, including myocardial infarction, are the leading cause of death in the western world. While great strides have been made in understanding the pathophysiology and treatment of myocardial infarction, further elucidation will undoubtedly lead to better treatment options in the future. Myocardial infarction is the death of cardiac tissue due to a loss of oxygen and nutrients. Myocardial infarction may be followed by cardiogenic shock, ventricular arrhythmia, or cardiac rupture which can be responsible for sudden death. The cardiac repair process involves inflammation and the removal of dead cells which are replaced by deposited granular tissue providing tensile strength to the damaged area. This study details the role of Junctional Adhesion Molecule-A in the pathogenesis of myocardial infarction and in the cardiac repair process. In order to determine the role of JAM-A in myocardial infarction, a surgical technique was utilized in which the left anterior descending coronary artery of wild type and Jam-A gt/gt mice was ligated, leading to a permanent ischemic injury. Following this procedure, Jam-A gt/gt mice exhibited an increased mortality rate attributed to cardiac rupture. Infarct size assessment revealed similar levels of initial injury between WT and JAM-A gt/gt mice. Contraction of the infarct occurred in both strains by 72 hours, but infarct size in Jam-A gt/gt mice was significantly greater at this timpoint. This indicated that JAM-A may play a role in the cardiac remodeling process. Jam-A gt/gt mice also were shown to develop heart failure 21 days following MI surgery. While Jam-A gt/gt mice exhibited a distinct cardiac rupture phenotype following MI, no changes in the transcript levels of inflammatory cytokines, matricellular proteins, and extracellular matrix proteins involved in the cardiac remodeling process were found. There was also no change in signaling associated with the VEGF angiogenic pathway or growth factor signaling through Akt. Finally, JAM-A was not found to be expressed in fibroblasts and could, therefore, not cause an alteration in their matrix deposition. These data suggest that JAM-A plays a cardioprotective role in the heart, protecting it from the adverse condition of cardiac rupture following MI. However, it is still unclear how JAM-A confers this protection.