The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis

Karan Sud, Navneet Narula*, Elena Aikawa, Eloisa Arbustini, Philippe Pibarot, Giampaolo Merlini, Robert S. Rosenson, Surya V. Seshan, Edgar Argulian, Amir Ahmadi, Fang Zhou, Andre L. Moreira, Nancy Côté, Sotirios Tsimikas, Valentin Fuster, Sam Gandy, Robert O. Bonow, Olga Gursky, Jagat Narula

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Original languageEnglish (US)
Pages (from-to)418-428
Number of pages11
JournalNature Reviews Cardiology
Volume20
Issue number6
DOIs
StatePublished - Jun 2023

Funding

P.P. has received grant funding from Cardiac Phoenix, Edwards Lifesciences, Medtronic and Pi-Cardia for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation; he has also received lecture fees from Edwards Lifesciences and Medtronic. R.S.R. has received research grants to his institution from Amgen, Arrowhead, NIH, Novartis and Regeneron, is a member of the advisory board of Amgen, Novartis, Regeneron and 89 Bio, has received honoraria for non-promotional speaking from Kowa, has stock holdings with MediMergent, and receives royalties from Wolters Kluwer (UpToDate). S.T. is a co-inventor who receives royalties from patents owned by University of California, San Diego on oxidation-specific antibodies and biomarkers related to oxidized lipoproteins, and is a co-founder who has equity interests in Kleanthi Diagnostics and in Oxitope and affiliates. Although these relationships have been identified for conflict of interest management based on the overall scope of the project and its potential benefit to Kleanthi and Oxitope, the research findings included in this particular publication do not necessarily relate to the interests of Kleanthi and Oxitope. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with conflict of interest policies. S.G. serves as a consultant for Altpep, Cognition Therapeutics, and Ritrova Therapeutics and is a founder of Recuerdo Pharmaceuticals (inactive), has served as a consultant in the past for Diagenic, has received research support in the past from Avid, Baxter, Pfizer and Warner-Lambert, and also receives compensation for chart review in connection with medical litigation in the area of cognitive function. The other authors declare no competing interests. E. Aikawa has received support from the NIH (grant numbers R01 HL136431, R01 HL141917 and R01 HL147095). S.G. has received support from the National Institute on Aging – Designated Alzheimer’s Disease Research Center (P50 AG005138 and P30 AG066514). O.G. has received support from the NIH (grants R01 GM067260 and R01 GM135158).

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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