Methods for treating myocardial infarction comprising adminis... by Alain Lacampagne

The spatial and temporal identification of the cells that are amenable to treatment is essential for the development of future and more effective therapies for MI. However, the physiological events that occur in the MI border zone are not well understood. Most newly developed therapies target the interface between the perfused and non-perfused areas of the heart, and they attempt to inhibit cardiomyocyte apoptosis or induce angiogenesis. One reason for the lack of adequate alternative therapies is that the target area and cells to be salvaged in the infarcted heart have not been identified, partly because MI patients typically have a variety of disease conditions. However, clinical trials involving vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) have not yielded the expected results 3, 4, 5 thus, no effective or innovative therapies have been developed for MI since catheter intervention became a widely used treatment. New treatments that use angiogenic or anti-apoptotic factors, and cell-based therapies are expected to alleviate heart damage. However, a subset of patients requires ventricular assistance devices or heart transplantations, because of the extreme impairment of cardiac function. Early thrombolysis and subsequent catheter intervention therapy during the acute phase reduce the size of the infarct and improve the prognoses of MI patients 1, 2. Myocardial infarction (MI) is a leading cause of death in westernized countries. These data indicate that the non-perfused area along the endocardium is a site of active angiogenesis and a promising target for MI treatment. In contrast, cardiomyocytes in the border zone’s hypoxic area underwent apoptosis within 12 h of MI, and the border area that was amenable to treatment disappeared. Moreover, enhanced angiogenesis increased cardiomyocyte survival along the endocardium in the ischemic zone and suppressed ventricular remodeling in infarcted hearts. Here, we describe a novel circulatory system wherein new vessels develop from the endocardium of the left ventricle to perfuse the hypoxic area and salvage damaged cardiomyocytes at 3–14 days after MI by activating vascular endothelial growth factor signaling. Identifying targets that benefit from angiogenesis treatment is indispensable for the development of revolutionary therapies. However, the mechanism and timing for new vessel formation in the mammalian heart following hypoxia are unclear. It has been speculated that the ischemic border zone is a unique area rescued by angiogenic therapy. Angiogenesis can reduce MI-induced damage by mitigating hypoxia. Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute and subacute phases of myocardial infarction (MI).

Methods for treating myocardial infarction comprising adminis... by Alain Lacampagne