News | Heart Failure | June 07, 2024

New Study Suggests that Amyloid Contributes to Calcific Aortic Valve Disease Development

“Much-needed pharmacologic interventions is paramount to better understand the complex modulators of the disease”

Calcific aortic valve disease (CAVD) is the major heart valve disease that afflicts nearly 10 million patients globally

Getty Images


June 7, 2024 — Calcific aortic valve disease (CAVD) is the major heart valve disease that afflicts nearly 10 million patients globally with an annual mortality exceeding 100,000, and the numbers continue to rise. In CAVD, microcrystals of hydroxyapatite (a calcium phosphate mineral) deposit onto the heart valve leaflets and impair cardiac function. The disease has a dismal prognosis with most untreated patients dying two years after diagnosis. Currently, the only available treatment is surgical aortic valve replacement, which is not appropriate for all patients.

While previous studies of the histology samples from explanted calcified aortic valves have found amyloid deposits in or near calcified areas, the causal relationship between amyloid deposition and calcification is unclear.

Researchers from Boston University Chobanian & Avedisian School of Medicine, in collaboration with clinical cardiologists from New York University and University of Texas Houston, have now proposed a molecular mechanism that links amyloid deposition in the aortic valve with degenerative calcification. They also theorize that other risk factors for CAVD, such as high blood levels of lipoprotein, can contribute to calcification both directly and indirectly through the mechanisms that involve amyloid accumulation.

Harnessing the “resolution revolution” in cryogenic electron microscopy, groups of researchers around the world were able to determine hundreds of structures of patient-derived protein aggregates called amyloid fibrils. Such fibrils are associated with major human diseases including Alzheimer’s and Parkinson’s diseases, diabetes, and heart diseases such as atherosclerosis and calcific aortic valve disease.  “We noticed that the unique geometry of amyloid fibrils, with their periodic arrays of acidic residues on the surface, provides a perfect match for the precursors of calcium phosphate crystals that deposit in the heart valve and impair its normal function,” explained corresponding author Olga Gursky, PhD, professor of pharmacology, physiology & biophysics at the school.

The researchers propose that amyloid deposits, which are often found adjacent to calcified areas of the heart valve, can modulate CAVD and accelerate degenerative calcification. This implies that blocking amyloid formation may be a much-needed novel therapeutic target for CAVD and, potentially, other diseases involving degenerative calcification and amyloid formation, such as Alzheimer’ disease.

“We hope that a better understanding of molecular mechanisms and drivers of degenerative biomineralization will help identify new therapeutic targets for major human diseases, such as calcific aortic valve disease,” adds Gursky.

These findings appear online in the journal Trends in Molecular Medicine.

For more information: https://www.cell.com/trends/molecular-medicine/home


Related Content

News | Cardiovascular Clinical Studies

Aug. 15, 2024 — According to a new study being presented at ACC Asia 2024 in Delhi, India, drinking over 400 mg of ...

Home August 14, 2024
Home
Videos | Cardiovascular Clinical Studies

As part of DAIC's continuing Thought Leadership Series, this month Editorial Director Melinda Taschetta-Millane sits ...

Home July 30, 2024
Home
News | Cardiovascular Clinical Studies

July 25, 2024 — BioCardia, Inc., a global leader in cellular and cell-derived therapeutics for the treatment of ...

Home July 25, 2024
Home
News | Cardiovascular Clinical Studies

July 18, 2024 — Elucid, a pioneering AI medical technology company providing physicians with imaging analysis software ...

Home July 18, 2024
Home
News | Cardiovascular Clinical Studies

July 10, 2024 — CellProthera, a private company specializing in cell-based therapies for repairing ischemic tissues, and ...

Home July 10, 2024
Home
News | Cardiovascular Clinical Studies

July 9, 2024 — Microbot Medical Inc. announced the completion of the first procedure in a patient utilizing its LIBERTY ...

Home July 09, 2024
Home
News | Cardiovascular Clinical Studies

June 26, 2024 — Semaglutide, a medication initially developed for type 2 diabetes and obesity, significantly improves ...

Home June 26, 2024
Home
News | Cardiovascular Clinical Studies

June 21, 2024 — Lexicon Pharmaceuticals, Inc. announced that the peer-reviewed Journal of the American College of ...

Home June 21, 2024
Home
News | Cardiovascular Clinical Studies

June 20, 2024 — Microbot Medical Inc. announced its agreement with Brigham and Women’s Hospital (BWH), a leading ...

Home June 20, 2024
Home
News | Cardiovascular Clinical Studies

June 20, 2024 — A programming algorithm, being tested by HonorHealth Research Institute for those patients with new or ...

Home June 20, 2024
Home
Subscribe Now