Pro- and anti-angiogenic therapy and atherosclerosis with special emphasis on vascular endothelial growth factors

Abstract

Even though pro-angiogenesis has been shown to be safe and well-tolerated in clinical trials, efficacy of the treatment has not been satisfactory. In the expert opinion section of the review, we discuss the major obstacles to cardiovascular gene therapy and some future prospects.

Arsenic modulates heme oxygenase-1, interleukin-6, and vascular endothelial growth factor expression in endothelial cells: roles of ROS, NF-κB, and MAPK pathways

“…IL-6, a proinflammatory cytokine present in atherosclerotic lesions (Seino et al 1994), and MCP-1, an essential chemokine involved in monocyte traffic across endo-and epithelial barriers both in vitro and in vivo, have been reported in arsenic-exposed experimental animals ). In addition, VEGF, a vascular permeability factor, has been implicated in inflammatory processes, intimal thickening and intra-plaque angiogenesis in atherosclerotic lesions (Vuorio et al 2012). Altogether, increased expression of these genes in SVEC4-10 cells may act as a risk factor of arsenic-induced vascular disorders.…”

“…Indeed, while up-regulation of HO-1 is regarded as cytoprotective under various experimental conditions (Cooper et al 2007;Lang et al 2005;Lee et al 2005), it can be detrimental to cells, as shown in this study and other conditions (Song et al 2007). In addition, it is evident that VEGF has both beneficial and unfavorable roles in the cardiovascular system (Weis and Cheresh 2005;Vuorio et al 2012).…”

Intussusceptive Angiogenesis: A Biologically Relevant Form of Angiogenesis

“…This form of angiogenesis results in a faster and better organized vascular plexus in comparison to SA. Current proangiogenic therapies mainly aim to induce SA, leading to the accumulation of fluid and transient edema in tissues [64]. This might be due to the leaky nature of newly formed vascular sprouts during SA.…”

“…The specific induction of IA after an initial colonization of angiogenic sprouts into the ischemic tissue could enhance vascular normalization, improving the therapeutic outcome. These proangiogenic therapies could be used in various forms of ischemic disease including ischemic heart diseases, large wound healing, and atherosclerosis [64]. …”

Receptor Tyrosine Kinase-Mediated Angiogenesis

“…Early on, clinical trials appeared to demonstrate the beneficial effect of both VEGF-A and VEGF-C therapy in cardiovascular disease. However, this strategy to improve cardiovascular function has not been translated into clinical practice (Losordo et al 2002;Reilly et al 2005;Stewart et al 2009;Vuorio et al 2012). The VEGFR-1 ligands PlGF and VEGF-B have both been proposed to play important roles during ischemic revascularization, especially in the heart.…”