Coordinated activation of VEGFR-1 and VEGFR-2 is a potent arteriogenic stimulus leading to enhancement of regional perfusion

Abstract

The coordinated activation of both VEGFR-1 and VEGFR-2 represents a more potent arteriogenic stimulus compared to the isolated activation of either one of these two receptors. These data imply that the activation of both monocytes and endothelial cells is necessary to obtain a maximal VEGF-induced activation of arteriogenesis.

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

“…ANG‐2 and PLGF were found to be the most abundantly secreted angiogenic growth factors, independent of underlying ischemic disease. Both ANG‐2 and PLGF play an important role in the complex cytokine cocktail, mediating the overall neovascularization process in ischemic disease 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47…”

Insulin activates hypoxia-inducible factor-1α in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling

“…The role of endogenous VEGF in arteriogenesis has recently been demonstrated, because VEGF receptor inhibition significantly reduced collateral vessel formation in a mouse model of hindlimb ischaemia [43].…”

PlGF: A Multitasking Cytokine with Disease-Restricted Activity

“…Conversely, PlGF protein or gene administration enhances angiogenesis, collateral vessel formation, and blood flow in surgically induced limb ischemia in mice, resulting in improved performance in endurance tests (Luttun et al 2002;Babiak et al 2004). Similar effects were seen in limb ischemia in the rabbit (Pipp et al 2003).…”

“…A possible implication of these findings is that PlGF blockade might inhibit disease processes more selectively than physiological homeostasis and thus evoke fewer side effects. We summarize below the findings on PlGF's (Foidart et al 2009;Furuya et al 2011) Heart PlGF-induced revascularization of ischemic myocardium and vessel enlargement in remote myocardium preserve cardiac performance following infarction (Luttun et al 2002;Kolakowski et al 2006;Roncal et al 2008) Knockout: impaired angiogenesis and inflammation in infarct border (Carmeliet et al 2001) Knockout: Normal exercise induces angiogenesis (Gigante et al 2004) Skeletal muscle PlGF protein or gene delivery: enhances angiogenesis, collateral growth, and blood flow in ischemic limb (Luttun et al 2002;Pipp et al 2003;Babiak et al 2004); restores microcirculation in aged dystrophic muscle (Gargioli et al 2008) Knockout: impaired collateral growth in ischemic limb (Carmeliet et al 2001;Scholz et al 2003;Gigante et al 2006) Knockout: normal exercise-induced angiogenesis (Gigante et al 2004) Eye PlGF prevents vessel obliteration in hyperoxia without including neovascularization (Shih et al 2003) Local ocular PlGF protein or gene transfer causes hematoretinal barrier breakdown and edema (Miyamoto et al 2007;Kowalczuk et al 2011) Knockout or aPlGF: impaired choroidal neovascularization (Carmeliet et al 2001;Rakic et al 2003;Van de Veire et al 2010) Knockout or aPlGF does not impair retinal vascularization during development (Carmeliet et al 2001;Feeney et al 2003 (Carmeliet et al 2001;Scholz et al 2003;Gigante et al 2006) (Eriksson et al 2002;Xu et al 2006;Schomber et al 2007;Tarallo et al 2010) PlGF educates CD34 þ progenitors to proangiogenic CD11b þ myelomonocytes in breast cancer (Laurent et al 2011...…”