Author + information
- Corey Tabit,
- Mitchell Coplan,
- Phetcharat Chen,
- Valluvan Jeevanandam,
- Nir Uriel and
- James Liao
Background: Non-surgical bleeding (NSB) due to angiodysplasia is common in patients with LVADs. We reported that thrombin-induced Angiopoietin-2 (Ang-2) expression in LVAD patients drives altered angiogenesis and is associated with decreased Angiopoietin-1 (Ang-1) expression. However, the mechanism for decreased Ang-1, which is made by pericytes, is not known and the etiology of thrombin activation in LVAD patients is not clear. We aimed to assess if high levels of Tumor Necrosis Factor-α (TNF-α) in patients with LVADs induce pericyte apoptosis, promote Tissue Factor (TF) expression, and promote vascular instability.
Methods: TNF-α and TF were measured by ELISA in blood from 101 patients with heart failure (HF), LVAD, or orthotopic heart transplant (OHT). Cultured pericytes were incubated with serum from each patient with/without TNF-α blockade. Ang-1 expression was measured by RT-PCR and pericyte death was measured by fluorescent live/dead stain. TF expression was measured by RT-PCR in cultured endothelial cells incubated with plasma from each patient with/without TNF-α blockade. TF expression in endothelial biopsy samples from these patients was measured by quantitative immunofluorescence. Cultured endothelial cells were incubated on Matrigel with serum from each patient with/without TNF-α blockade and tube formation was assessed by microscopy.
Results: LVAD patients had higher levels of TNF-α compared with HF or OHT. Serum from LVAD patients suppressed Ang-1 expression in pericytes and induced pericyte death more than serum from HF or OHT patients. Both plasma and endothelial cells from LVAD patients contained higher amounts of TF, and plasma from LVAD patients induced more endothelial TF expression than plasma from HF or OHT patients. Serum from LVAD patients had more angiogenic potential than serum from HF or OHT patients. All of these effects of LVAD serum were reversed or reduced with TNF-α blockade. Interestingly, all NSB events in the LVAD cohort occurred in patients with high levels of TNF-α.
Conclusions: Elevated TNF-α in LVAD patients regulates altered angiogenesis, pericyte apoptosis, and TF expression. TNF-α blockade may reduce vascular complications in LVAD patients.
Room 144 A
Saturday, March 18, 2017, 8:51 a.m.-9:01 a.m.
Session Title: Highlighted Original Research: Heart Failure and Cardiomyopathies and the Year in Review
Abstract Category: 13. Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 902-10
- 2017 American College of Cardiology Foundation