Abstract 451: Systemic Ventricular Pressure Loading Plays a Negative Role in Self-repair of the Injured Heart
Background — Mitotic cardiomyocytes and cardiac stem cells were recently identified in adult hearts, and found to be increased in acutely infarcted myocardium. Although these findings suggest potential self-repair of the heart after injury, obvious self-regeneration of the injured heart has never been observed clinically. We hypothesized that ventricular pressure loading plays a negative role in myocardial repair, creating a negative balance between myocardial regeneration and loss.
Methods — Myocardial infarction was induced in C57BL/6 mice by ligating the left anterior descending artery. After 60 min, the infarcted hearts were either transplanted heterotopically into healthy C57BL/6 mice, to remove the ventricular pressure loading (Unloading Group), or left in the same mice under normal pressure loading conditions (Loading Group). To compare the regeneration of infarcted hearts under pressure loading and unloading conditions, we dissected the hearts for histological analysis after 3, 7, 14, and 28 days. The left ventricular wall thickness and area of infarction were measured 28 days after heart injury, and the number of stem cells, mitotic cells, and apoptotic cells were determined quantitatively, 3 and 7 days after heart injury.
Results — The wall thickness of the infarcted left ventricle was significantly thicker, and the area of infarction was significantly smaller in the Unloading group than in the Loading group. Immunostaining analysis showed that the number of c-kit- and Sca-1-positive stem cells in infarcted myocardium were higher in the Unloading group than in the Loading group. There were significantly more Ki-67 positive cells, but significantly fewer TUNEL-positive apoptotic cells in the infarcted myocardium in the Unloading group than in the Loading group. Interestingly, fewer Ki-67 positive cells than apoptotic cells were counted in the Loading group, but more Ki-67 positive cells than apoptotic cells were counted in the Unloading group.
Conclusion — Our findings suggest that systemic ventricular pressure loading plays a negative role in self-repair of the injured heart. Thus, reducing pressure loading may be a new strategy to assist self-regeneration of the injured heart.