Gene therapy vector-mediated expression of insulin-like growth factors protects cardiomyocytes from apoptosis and enhances neovascularization

Abstract

therapy vectormediated expression of insulin-like growth factors protects cardiomyocytes from apoptosis and enhances neovascularization.

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

“…27,29,41 The most important difference between HB-EGF and HGF/IGF, which accounts for the observed discrepancy, is the lack of a direct cytoprotective effect of HB-EGF on cardiomyocytes, in contrast to the potent cytoprotective effect observed for HGF and IGF in injured hearts. 27,29,41 This is a unique feature of HB-EGF, because most organogenic and/or organotrophic growth factors exert direct antiapoptotic effects, for example, HGF or IGF in mouse or rat cardiomyocytes [26][27][28][29] and HB-EGF in the small intestine. 42 In this regard, future studies to explore the differences among the molecules and signal transduction pathways involved in the activity of each growth factor would be biologically important.…”

“…It should be noted that improvement of cardiac dysfunction after MI has been successfully achieved by gene therapy using angiogenic factors that do not directly act on cardiomyocytes. 29,43 This fact suggests that angiogenesis plays a crucial role in postinfarction remodeling, and that the absence of an angiogenic effect of overexpressed HB-EGF may be largely responsible for its lack of therapeutic action.…”

“…24,25 However, overexpression of HGF and IGF induced cardiac hypertrophy, but inconsistently exhibited potent therapeutic and beneficial effects on the injured heart, including that damaged by MI. [27][28][29] Taken together with these facts, HB-EGF-induced cardiac hypertrophy may not be a sole or direct source of pathogenesis in MI, even though cardiac hypertrophy may, in fact, be involved in specific types of heart failure. In this context, the present results importantly imply that HB-EGFinduced exacerbation of remodeling may be a novel pathological mechanism for MI.…”

“…24,25 However, several previous studies demonstrated that overexpression of hepatocyte growth factor (HGF) and insulin-like growth factor (IGF), which are also cardiogenic growth factors, significantly induced cardiac hypertrophy but had potent therapeutic rather than pathologic effects in injured hearts, including those damaged by MI. [26][27][28][29] This led us to question whether HB-EGF might also possess therapeutic activity in the injured heart. Intriguingly, were HB-EGF to prove pathogenic, it could be the result of a secondary biological effect of this molecule separate from its promotion of hypertrophy.…”

A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle

“…The latter examined cytokine responses to SDF-1 delivery in a synthetic scaffold; however, our results also suggest that the SDF-1 microsphere matrix supports a favourable environment for angiogenic activity through local factors, as evidenced by increased IGF-1 and VCAM-1 in hindlimb lysates. IGF-1 is a stimulator of angiogenesis (Su et al, 2003) and is cytoprotective (Li et al, 1997), and elevated IGF-1 is ideal for recovery. Pelosi et al (2007) have shown that persistent IGF-1 expression accelerates the regenerative response and restores architecture and structure soon after skeletal muscle injury.…”