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Cholesterol induced heart valve inflammation and injury: efficacy of cholesterol lowering treatment
  1. Layan A El-Khatib1,
  2. Heather De Feijter-Rupp2,
  3. Abed Janoudi2,
  4. Levi Fry2,
  5. Michael Kehdi2 and
  6. George S Abela2,3
  1. 1Internal Medicine, Henry Ford Hospital, Detroit, Michigan, USA
  2. 2Department of Medicine, Division of Cardiovascular Medicine, Michigan State University College of Human Medicine, East Lansing, Michigan, USA
  3. 3Department of Physiology, Division of Pathology, Michigan State University, East Lansing, Michigan, USA
  1. Correspondence to George S Abela; abela{at}


Background Heart valves often undergo a degenerative process leading to mechanical dysfunction that requires valve replacement. This process has been compared with atherosclerosis because of shared pathology and risk factors. In this study, we aimed to elucidate the role of inflammation triggered by cholesterol infiltration and cholesterol crystals formation causing mechanical and biochemical injury in heart valves.

Methods Human and atherosclerotic rabbit heart valves were evaluated. New Zealand White male rabbits were fed an enriched cholesterol diet alone or with simvastatin and ezetimibe simultaneous or after 6 months of initiating cholesterol diet. Inflammation was measured using C-reactive protein (CRP) and RAM 11 of tissue macrophage content. Cholesterol crystal presence and content in valves was evaluated using scanning electron microscopy.

Results Cholesterol diet alone induced cholesterol infiltration of valves with associated increased inflammation. Tissue cholesterol, CRP levels and RAM 11 were significantly lower in simvastatin and ezetimibe rabbit groups compared with cholesterol diet alone. However, the treatment was effective only when initiated with a cholesterol diet but not after lipid infiltration in valves. Aortic valve cholesterol content was significantly greater than all other cardiac valves. Extensive amounts of cholesterol crystals were noted in rabbit valves on cholesterol diet and in diseased human valves.

Conclusions Prevention of valve infiltration with cholesterol and reduced inflammation by simvastatin and ezetimibe was effective only when given during the initiation of high cholesterol diet but was not effective when given following infiltration of cholesterol into the valve matrix.

  • aortic valve disease
  • mitral regurgitation
  • pulmonary valve disease
  • atherosclerosis

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  • Contributors LAE-K contributed to writing the manuscript and data analysis. HD-R collected data and processed tissue for SEM. AJ conducted data analysis and helped in writing the manuscript. LF and MK reviewed the manuscript and provided critique. GA wrote the manuscript and provided data interpretation.

  • Funding Department of Medicine and College of Human Medicine, Michigan State University, East Lansing, Michigan, Merck-Schering/Plough, Kenilworth, NJ. and Edward Sparrow Hospital, Lansing, MI.

  • Competing interests GA is a speaker for Amgen and Kowa Pharmaceutical. He is a former recipient of grant from Merck.

  • Patient consent for publication Not required.

  • Ethics approval This protocol was approved by Michigan State University’s Animal Care and Use Committee following National Institute of Health guidelines (Institutional Animal Care and Use Committee # 03/18-034-01).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data is presented and anlaysed in the manuscript.

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