Modulation of p53 by DUSP4 Serves a Novel Therapeutic Strategy in the Treatment of Ischemic Heart Disease via Promoting Angiogenesis

After an ischemia and reperfusion (I/R) injury, reestablishing blood flow to the infarct region can salvage myocardium by clearing apoptotic cells, removing scar tissue, stimulating angiogenesis, and recruiting progenitor cells for tissue regeneration. Stimulating the growth of new microcirculation in the infarct area can help revive cardiac function. Angiogenesis is a process of developing new blood vessels from the existing vessels. Our previous work on Dual specificity phosphatase 4 (DUSP4) demonstrated that DUSP4 -/- hearts sustain a larger infarct and have poor functional recovery, when isolated hearts were subjected to I/R. Uncontrolled p38 activation is the main effectors for this functional alteration. In this study, DUSP4 overexpression in endothelial cells was used to investigate the role of DUSP4 in the development of vascular function, and its role against oxidant stress. DUSP4 overexpression promotes angiogenesis and tube formation (increased by 57.3% ± 6.2% versus control; p