Tachycardia pacing induces myocardial neovascularization and mobilizes circulating endothelial progenitor cells partly via SDF-1 pathway in canines

Abstract

Neovascularization plays pivotal role in ischemic heart failure; however, it is unclear in non-ischemic heart failure. Non-ischemic heart failure was induced by chronic rapid right ventricular pacing at 200 beats/min, respectively, for 3 and 6 weeks in 12 dogs. Sham-operation was performed in another 6 dogs as control. Three-week tachycardia pacing could induce mild/moderate heart failure and 6-week pacing could induce severe heart failure. Pan-microvessel density (MVD) was assessed by CD31 and neovascularization density was assessed by CD105. Mean CD31-MVD and CD105-MVD were significantly increased after 3-week pacing. However, CD105-MVD was significantly decreased by 80 % in 6-week pacing group compared with 3-week pacing group, whereas CD31-MVD was only decreased slightly (15 %; P < 0.05). Myocardial proangiogenic factor stromal cell-derived factor 1 (SDF-1), hypoxia-inducible factors 1α (HIF-1α, a transcription factor which could regulate SDF-1 expression), serum SDF-1 levels and circulating EPC mobilization were greatly elevated after 3-week pacing but nearly returned to baseline level after 6-week pacing, which were in accordance with the changes of neovascularization levels assessed by CD105. Angiogenesis and migrating ability of EPCs were enhanced after stimulation of SDF-1, which could be abolished by pretreatment with SDF-1 receptor antagonist AMD3100. In addition, angiogenesis and migrating functions of EPCs were significantly enhanced by the serum from 3-week pacing dogs, but had much weaker response to the serum from 6-week pacing dogs. In conclusion, tachycardia pacing-induced non-ischemic heart failure, promoted myocardial neovascularization and mobilized circulating EPCs, which might be mediated partly through SDF-1 pathway.

The impact of cardiomotor rehabilitation on endothelial function in elderly patients with chronic heart failure

“…EPC increased significantly in the early stage of HF, promoted angiogenesis, and protected endothelial cell function from restoring myocardial blood supply and improving myocardial function. At the same time, EPC decreased significantly in the late stage of heart failure [ 21 ]. Anti-heart failure treatments can improve the number of EPC in peripheral blood of patients with heart failure, promote the proliferation and migration of EPCs.…”

Prospects for the Use of Umbilical Cord Blood in the Treatment of Diseases of the Cardiovascular System

“…Indeed, it is well known that some of the mentioned substances contribute to the proliferation, recruitment (accumulation) and survival of SC in the tissues of the recipient. Thus, SDF helps the homing of progenitor cells [30,37,38], T4 promotes cell migration, bFGF enhances the proliferation of endothelial and smooth muscle cells, G-CSF accelerates the proliferation and differentiation of neutrophils, M-CSF enhances the proliferation and differentiation of monocytes, SFRP1accelerates cell development, SFRP2accelerates cell development and inhibits apoptosis IGF-1 -regulates cell growth and proliferation, inhibits apoptosis [31]. Factors of angiogenic action are important components of SC secretomes in the aspect of protection and restoration of heart tissues: VEGF -stimulates proliferation and migration of endothelial cells, formation of blood vessels [30], FGF-7 -induces proliferation of endothelial cells, FGF-2 -induces proliferation of endothelium and smooth muscle muscles, PDGFstimulates the proliferation of smooth muscles, MCP-1 -enhances angiogenesis, promotes the re cruit ment of monocytes, PlGF -promotes angiogenesis, TGF-accelerates cell maturation.…”