Background-Recombinant human vascular endothelial growth factor protein (rhVEGF) stimulates angiogenesis in animal models and was well tolerated in Phase I clinical trials. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF. Methods and Results-A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng · kg Ϫ1 · min

Compared with on-label use, off-label use of drug-eluting stents is associated with a higher rate of adverse outcomes during the index admission and at 1 year. Stent thrombosis occurred predominantly in patients who underwent off-label drug-eluting stent implantation. Clinicians should be cautious about extrapolating the benefits of drug-eluting stents over bare-metal stents observed in randomized clinical trials to higher-risk clinical settings that have not been assessed.

This mechanism-based model accurately predicted VEGF concentrations and allowed for the simulation of various rhVEGF(165) dose regimens that may aid in optimization of drug delivery for future clinical trials.

Coronary occlusive disease is the leading cause of death in industrial nations and affects one in four adults. Although heart attacks are caused by occlusion of a coronary artery, some patients have occlusions without infarction because they have sufficient collateral vessels providing an alternate pathway for blood supply. Vascular endothelial growth factor (VEGF) is an angiogenic peptide that can stimulate collateral vessel development in the ischaemic myocardium. We used magnetic resonance imaging (MRI) and image processing to identify and quantify non-invasively the benefits related to VEGF infusion on collateral development in the heart. This was accomplished as a placebo-controlled study in the porcine model of chronic ischaemia that most closely mimics the human pathophysiology of progressive coronary occlusion. Image series converted to a space-time map demonstrated that with treatment the ischaemic zone was smaller and the contrast arrival delay was less, which resulted in better ejection fraction and regional wall thickening. These findings demonstrate in a manner applicable to humans, that VEGF improves collateral blood supply, resulting in improved cardiac global and regional function after and in spite of coronary artery occlusion.

Aspects of conformational transitions, folding, and misfolding of peptides and proteins have moved into the center of interest in various domains of research at the interface of chemistry, biology, and medicine because of their impact on neurodegenerative diseases.[1] For example, recent research suggests that conformational transitions of soluble amyloid b precursor molecules into aggregated, b-sheet-type forms play a key role in the deposition of cerebral amyloid plaques

Vascular endothelial growth factor (VEGF) is a potent mitogen capable of stimulating angiogenesis. We examined the effect of VEGF administration in a model of chronic porcine myocardial ischemia. Nineteen pigs were instrumented with proximal left circumflex coronary artery (LCX) Ameroid constrictors. In eight animals VEGF (2 microgram) with heparin (50 U) was administered extraluminally to the LCX myocardium with an osmotic pump for 4 wk and 11 other animals served as controls. VEGF-treated animals demonstrated higher flow in the LCX territory during both rest and pacing compared with untreated controls (rest: 1.35 +/- 0.1 vs. 0.80 +/- 0.09 ml.min-1.g-1; pacing; 2.01 +/- 0.37 vs. 1.01 +/- 0.07 ml.min-1.g-1, P < 0.05, VEGF vs. controls). The observed improvement in regional coronary flow in VEGF-treated animals resulted in better preservation of endothelium-dependent microvessel relaxation as well as fractional LV shortening in the LCX territory during pacing in the VEGF-treated than in control animals (controls: 7.1 +/ 2.6 vs. 3.6 +/- 2.0%, rest vs. pacing; VEGF: 6.9 +/- 2.9 vs. 6.3 +/- 2.9%, rest vs. pacing). We conclude that VEGF administration in a gradual coronary occlusion model in pigs results in improvement of coronary flow and preservation of regional hemodynamics in the compromised myocardium.

Renal function is an independent and powerful predictor of bleeding and ischemic complications in the era of DES and contemporary antithrombotic therapy in patients undergoing PCI. The low use of guideline-recommended drugs among patients with CKD undergoing PCI might contribute to these adverse outcomes and warrants further evaluation.

Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.