Key result
Decreased HMW VWF and elevated ANGPT-2 linked to post-CF-LVAD bleeding and angiogenesis.
Why the study?
Do VWF and ANGPT-2 levels predict non-surgical bleeding in CF-LVAD patients?
Observational (n=19)
Do VWF and ANGPT-2 levels predict non-surgical bleeding in CF-LVAD patients?
VWF and ANGPT-2 work cooperatively to induce angiogenesis and may serve as biomarkers for predicting non-surgical bleeding risk in CF-LVAD patients.
Background: Continuous Flow Left Ventricular Assist Devices (CF-LVADs) are the gold standard therapy for heart failure (HF) patients. Although this therapeutic approach is associated with improved clinical outcomes, CF-LVAD patients experience non-physiological reductions in arterial pressure and flow pulsatility, which are linked to an increased risk of nonsurgical bleeding, and arteriovenous malformations (AVMs). Studies suggest reduced pulsatility leads to von Willebrand factor (VWF) degradation and Angiopoietin-2 (ANGPT-2) induction in the bloodstream. While their interaction in endothelial cells is observed, their combined effects in CF-LVAD patients are underexplored. This study evaluates the cooperative effect of VWF and ANGPT-2 on non-surgical bleeding in CF-LVAD patients. Methods: First, we quantitatively assessed VWF and ANGPT-2 levels in the blood of CF-LVAD patients (n=19), both before VAD implantation and monthly thereafter, using ELISA and Western blotting. The impact of pulsatility loss on VWF/ANGPT-2 status and angiogenesis was assessed using an in vitro vascular pulse perfusion model (VPPM). Plasma samples from CF-LVAD patients were analyzed for VWF and ANGPT-2 complexes via immunoprecipitation. Additionally, endothelial cells were treated with recombinant ANGPT-2 and VWF to assess angiogenic marker expression. Results: High molecular weight (HMW) VWF levels significantly decreased in all CF-LVAD patients. In contrast, ANGPT-2 levels transiently increased in patients experiencing bleeding, whereas LVAD patients without bleeding showed decreased ANGPT-2 levels. Our results suggest that increased ANGPT-2 and the loss of HMW-VWF may predict bleeding in CF-LVAD patients. Using VPPM, we mimicked the stretch generated during CF-LVAD flow and observed induced angiogenesis, with marked upregulation of VWF and ANGPT-2. Next, we evaluated the cooperative promotion of angiogenesis by VWF and ANGPT-2. Immunoprecipitation confirmed the presence of VWF and ANGPT-2 complexes in patients’ plasma. Treatment of endothelial cells with recombinant ANGPT-2 and VWF proteins significantly increased the expression of angiogenic markers at both the transcriptional and translational levels. Conclusion: Our data reveal that VWF and ANGPT-2 work cooperatively in developing non-surgical bleeding, potentially by inducing angiogenesis, and can serve as biomarkers for predicting bleeding risk and guiding treatment in CF-LVAD patients.
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Sah et al. (2025) conducted an observational in Heart failure with Continuous Flow Left Ventricular Assist Devices (CF-LVAD) (n=19). VWF and ANGPT-2 levels vs. CF-LVAD patients without bleeding was evaluated on Non-surgical bleeding and angiogenesis marker expression. In 19 CF-LVAD patients, high molecular weight VWF decreased and ANGPT-2 transiently increased in those with bleeding, suggesting they work cooperatively to induce angiogenesis and bleeding.
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