Angiopoietin-1 for Myocardial Angiogenesis

In response to ischemic damage, the heart undergoes vicious process of remodeling wherein the damaged myocardium is replaced by scar tissue and as compensatory mechanism, its existing collateral vessels and neovascularization with concomitant changes in cell recruitment, multiplication and cytokine/growth factor action. Angiogenesis is a complex process which involves an interplay between multiple proand anti-angiogenic factors and a harmonized interaction between endothelial progenitor cells, smooth muscle cells, pericytes and supportive environment. Besides Vegf/ Vegf receptor system, angiopoietin family of pro-angiogenic growth factors in conjunction with their receptor system are critical for vascular protection, remodeling, proliferation and maturation beside preservation of the integrity of newly formed vascular structures for functional activity (Thurston et al. 2000; Saharinen et al. 2005; Brindle, Saharinen et al. 2006). An outside intervention to support the inefficient intrinsic myocardial repair processes by administration of stem/ progenitor cells has emerged as a promising strategy for the treatment of ischemic heart diseases. The transplanted stem cells have shown both myogenic as well as vasculogenic differentiation potential and participate in the myocardial regeneration via angiomyogenesis (Chen et al. 2010; Uemura et al. 2006; Eguchi et al. 2007). In addition to differentiation, stem cells can also ameliorate inflammation, migrate to ischemic regions and secrete bioactive molecules as a part of their paracrine activity and significantly contribute myocardial protection and angiogenesis. Alternatively, multimodal therapeutic strategies have also been adopted to accentuate the angiomyogenic potential of stem cells. This includes preconditioning of stem cells with growth factor treatment, their genetic modification with plasmids encoding for various angiogenic growth factors and concomitant administration of recombinant angiogenic growth factor proteins (Jiang et al. 2006; Haider et al. 2008; Kim et al. 2009; Lu et al. 2009). Such multimodal treatment strategies have elicited beneficial effects in terms of improving stem cell survival and enhancing their paracrine behavior besides stimulation of angiogenesis through direct recruitment, proliferation and maturation of precursor cells such as endothelial progenitor cells, mesenchymal stem cells and monocytes to the ischemic heart (Banai et al. 1994; Hiasa et al. 2004; Elmadbouh et al. 2007; Haider et al. 2008). We discuss here the biological regulation of angiopoietin-1 expression, its interaction with specific receptor system and the advantages of transgenic over expression of angiopoietin-1 either alone or in combination