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Updated: Oct 15, 2025
Studying Left Ventricular Reverse Remodeling by Aortic Debanding in Rodents
Published on: July 14, 2021
Matrix-Degrading Enzyme Expression and Aortic Fibrosis During Continuous-Flow Left Ventricular Mechanical Support
Amrut V Ambardekar1, Matthew S Stratton1, Evgenia Dobrinskikh2
1Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Continuous-flow (CF) left ventricular assist devices (LVADs) cause aortic remodeling and fibrosis, linked to support duration. This occurs due to suppressed matrix-degrading enzymes, highlighting potential areas for therapeutic intervention.
Area of Science:
- Cardiovascular Science
- Biomedical Engineering
- Translational Medicine
Background:
- Nonphysiological blood flow from continuous-flow (CF) left ventricular assist devices (LVADs) can impact aortic tissue, but the specific effects are not fully understood.
- Understanding vascular remodeling in response to CF-LVADs is crucial for improving patient outcomes.
Purpose of the Study:
- To quantify fibrosis in the aorta after CF-LVAD implantation.
- To determine the molecular changes in aortic tissue associated with CF-LVAD support.
Main Methods:
- Paired aortic tissue samples were collected from 22 patients at CF-LVAD implantation and subsequent heart transplant.
- Aortic wall morphometry, collagen content (fibrosis), and whole-transcriptome RNA sequencing were performed.
- Immunohistochemistry was used to validate RNA sequencing findings for specific gene and protein expression.
Main Results:
- A significant increase in adventitial layer thickness and collagen intensity in the intima and media was observed post-CF-LVAD.
- Increased fibrosis correlated with longer durations of CF-LVAD support.
- CF-LVAD support led to decreased expression of extracellular matrix-degrading enzymes, with no evidence of fibroblast activation.
Conclusions:
- Aortic remodeling and fibrosis occur after CF-LVAD implantation, with severity related to support duration.
- The observed fibrosis is partly attributed to the downregulation of extracellular matrix-degrading enzymes.
- Further investigation into nonphysiological flow effects and pulsatility modulation is warranted to improve vascular remodeling and long-term outcomes.
