Author + information
- Received March 24, 2020
- Revision received June 2, 2020
- Accepted June 2, 2020
- Published online August 24, 2020.
- Antonio Frasca, PhDa,
- Yingfei Xue, PhDa,
- Alexander P. Kossar, MDa,
- Samuel Keeney, BSb,
- Christopher Rock, PhDb,
- Andrey Zakharchenko, PhDb,
- Matthew Streeter, PhDc,
- Robert C. Gorman, MDd,
- Juan B. Grau, MDe,
- Isaac George, MDa,
- Joseph E. Bavaria, MDd,
- Abba Krieger, PhDd,
- David A. Spiegel, PhDc,
- Robert J. Levy, MDb and
- Giovanni Ferrari, PhDa,∗ ()
- aDepartment of Surgery, Columbia University, New York, New York
- bDepartment of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- cDepartment of Chemistry, Yale University, New Haven, Connecticut
- dDepartment of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
- eOttawa Heart Institute, Ottawa, Ontario, Canada
- ↵∗Address for correspondence:
Dr. Giovanni Ferrari, Departments of Surgery and Biomedical Engineering. Columbia University, 630 West 168th Street, 17.413, New York, New York 10032.
• Two novel and interacting mechanisms contributing to BHV SVD are reported: glycation and serum albumin infiltration.
• Glycation product formation and serum albumin deposition were observed in 45 clinical BHV explanted due to SVD as well as BHV tissue subcutaneously implanted in rats.
• In vitro exposure to glycation and serum albumin elicited collagen network misalignment similar to that seen in clinical and rat explant BHV tissue.
• Glycation was sufficient to impair BHV hydrodynamic function in ISO-5840-compliant pulse duplication testing and concomitant serum albumin infiltration exacerbated these effects.
Valvular heart diseases are associated with significant cardiovascular morbidity and mortality, and often require surgical and/or percutaneous repair or replacement. Valve replacement is limited to mechanical and biological prostheses, the latter of which circumvent the need for lifelong anticoagulation but are subject to structural valve degeneration (SVD) and failure. Although calcification is heavily studied, noncalcific SVD, which represent roughly 30% of BHV failures, is relatively underinvestigated. This original work establishes 2 novel and interacting mechanisms—glycation and serum albumin incorporation—that occur in clinical valves and are sufficient to induce hallmarks of structural degeneration as well as functional deterioration.
This work was supported by National Institutes of Health grants R01s HL122805 (to Dr. Ferrari) and HL143008 (to Drs. Levy and Ferrari), T32s HL007915 (to Drs. Levy and Rock), HL007854 (to Dr. Kossar) and HL007343 (to Dr. Frasca), The Kibel Fund for Aortic Valve Research (to Drs. Ferrari and Levy), The Valley Hospital Foundation ’Marjorie C Bunnel’ charitable fund (to Drs. Ferrari and Grau), the American Diabetes Association Pathway to Stop Diabetes Grant 1-17-VSN-04 and the SENS Research Foundation (to Dr. Spiegel), and both Erin’s Fund and the William J Rashkind Endowment of the Children’s Hospital of Philadelphia (to Dr. Levy). Dr. Spiegel is cofounder and chief scientific adviser at REVEL Pharmaceuticals. Dr. Levy is a consultant for WL Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 24, 2020.
- Revision received June 2, 2020.
- Accepted June 2, 2020.
- 2020 The Authors