Abstract 15777: Vascular Density and Fibrosis in Heart Failure Recovery

Abstract

Introduction: Chronic unloading with a left ventricular assist device (LVAD) leads to LV remodeling including increased endothelial density, reduction of fibrosis, and improved cardiac function. Specific mechanisms of such recovery have not been fully explored in humans. Hypothesis: We hypothesize that recovery from non-ischemic heart failure is accompanied by increased vascular density and reduction in fibrosis. Methods: We developed and characterized a murine model of non-ischemic heart failure (HF) and recovery (HFR) using Angiotensin II infusion pumps and L-NAME/NaCl in water for 5 weeks followed by removal of these insults to induce a recovery. Ejection fraction, LV mass, fibrosis, and vessel density were assessed at various time points. We quantified vessel density using fluorescent microsphere bead perfusion and measured fibrosis using Masson’s Trichrome staining. Statistical analysis was performed using One way ANOVA, n=5 mice/group with 2 replicate experiments. ( p <0.05 was considered significant.)Results: LV mass and interstitial fibrosis increased significantly while ejection fraction and vascular density showed significant decreases in HF vs control mice while recovering hearts showed normalized ejection fraction and LV mass with a significant reduction in fibrosis. There was a very significant increase in vascular density when compared to HF mice (Fig. 1). Together, these preliminary data support our hypothesis that recovery from heart failure involves a vascular recovery. Conclusions: Morphological recovery of cardiac function is accompanied by an increase in vascular density along with a reduction in fibrosis in a non-ischemic mouse model of heart failure recovery. This increase in vascular density may be a required component of the recovery process from heart failure and further studies are necessary to understand the specifics of such mechanisms.