Abstract 4572: Reduced Cardiac Progenitors in the Right Ventricle of Cyanotic Heart Lesions: Insights into RV Adaptation
The RV in hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF) is exposed to hypoxia and abnormal load which may lead to RV dysfunction despite surgical repair. The ability of hypoxia to upregulate angiogenic signaling in the RV is not known. We measured vascular endothelial growth factor (VEGF) mediated regulation of cardiac progenitors in the RV of patients with HLHS and TOF.
Methods: RV myocardial samples were obtained from 6 pts with HLHS (age 0.96±1.5 yrs), 6 pts with TOF (age 3.5±6.3 yrs) and 9 age-matched controls with structurally normal hearts (age 0.16±0.3 yrs) at surgery/transplant/autopsy. The following were measured: VEGF, thymosin β-4 (recruits progenitors), Nkx2.5 (myocyte precursor), Flk-1 (smooth muscle progenitor), CD34 (endothelial progenitor), and von willebrand factor (vWf) (endothelial marker).
Results: (i) VEGF and thymosin β-4 expression was lower in HLHS vs controls. This was associated with reduced cardiac progenitors and lower myocardial capillary density vs controls (0.14±0.01 vs 0.55±0.16, p<0.05). (ii) VEGF expression was preserved but thymosin β-4 was reduced in RV in TOF. This was associated with preserved myocyte progenitors but reduction in endothelial and smooth muscle lineages and reduced capillary density vs controls (0.13±0.03 vs 0.55±0.16, p<0.05) (Figure 1⇓).
Conclusion: Hypoxia fails to induce an angiogenic response in the RV in cyanotic heart lesions. This may be due to reduced VEGF (HLHS) or impaired coupling of VEGF to thymosin β-4 (TOF). This maladaptation may contribute to post-operative RV dysfunction and lower RV regenerative capacity in later life.