Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

Abstract

This review is intended to discuss the newly discovered role of preconditioning which should make it an attractive therapeutic stimulus for repairing the injured myocardium. We recently found that apart from rendering the myocardium tolerant to ischemic reperfusion injury, preconditioning also potentiates angiogenesis. Our study demonstrated for the first time that both ischemic and hypoxic preconditioning triggered myocardial angiogenesis at the capillary and arteriolar levels which nicely corroborated with the improved myocardial contractile function. Hypoxic preconditioning resulted in the stimulation of VEGF, the most potent angiogenic factor known to date. In concert, endothelial cell specific tyrosine kinase receptors, Tie 1, Tie 2 and Flt-1 and Flk-1 were also significantly enhanced in the preconditioned myocardium. The redox-regulated transcription factor NFkB was found to play an essential role in the preconditioning regulation of angiogenesis.

Redox regulation of angiotensin II siganling in the heart

“…It is apparent that during the earlier phase, the heart attempts to adapt itself against the detrimental effects of angiotensin II by upregulating several cardioprotective genes and proteins. These genes and proteins are redoxregulated and their expressions are blocked by the antioxidants or ROS scavengers [87,88]. An identical pattern of cardioprotective proteins and genes are expressed in the preconditioned heart, which are also inhibited with ROS scavengers.…”

Potential candidates for ischemic preconditioning-associated vascular growth pathways revealed by antibody array

“…It was already reported that activation of MAPK pathway together with inhibition of SAPK/JNK activity by VEGF is the key event in determining whether an endothelial cell is going to survive or will undergo programmed cell death (8). JNK is crucial to programmed cell death induced by TNF receptor, and one mechanism by which NF-B protects cells is downregulation of the JNK cascade through the transcriptional activation of Gadd45␤ (4).…”

Redox-Dependent Mechanisms in Coronary Collateral Growth: The “Redox Window” Hypothesis

“…Several observations support the contention that the process of collateral growth is multifactorial. Matsunaga et al (61) observed that vascular endothelial growth factor (VEGF) was , play a key role in many cardiovascular pathologies, such as atherosclerosis and ischemia=reperfusion injury (51,64,67). Moreover, patients with congestive heart failure (CHF) show signs of oxidative stress, and the link between this stress and the progression of CHF is being explored (70).…”