Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?
Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stim...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/12/3331 |
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| author | Mohamed J. Nsaibia Anichavezhi Devendran Eshak Goubaa Jamal Bouitbir Romain Capoulade Rihab Bouchareb |
| author_facet | Mohamed J. Nsaibia Anichavezhi Devendran Eshak Goubaa Jamal Bouitbir Romain Capoulade Rihab Bouchareb |
| author_sort | Mohamed J. Nsaibia |
| collection | DOAJ |
| description | Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis. |
| first_indexed | 2024-03-09T23:28:24Z |
| format | Article |
| id | doaj.art-9095afc9daa1453ea22b16c5f75487ba |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:28:24Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-9095afc9daa1453ea22b16c5f75487ba2023-11-23T17:14:14ZengMDPI AGJournal of Clinical Medicine2077-03832022-06-011112333110.3390/jcm11123331Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?Mohamed J. Nsaibia0Anichavezhi Devendran1Eshak Goubaa2Jamal Bouitbir3Romain Capoulade4Rihab Bouchareb5Department of Cell Biology and Molecular Medicine, Rutgers University, Newark, NJ 07103, USADepartment of Medicine, Cardiovascular Research Institute, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAThomas Jefferson University East Falls, Philadelphia, PA 19144, USADepartment of Pharmaceutical Sciences, Division of Molecular and Systems Toxicology, University of Basel, 4056 Basel, SwitzerlandL’institut Du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceDepartment of Medicine, Division of Nephrology, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACalcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis.https://www.mdpi.com/2077-0383/11/12/3331aortic valvelipidsstatinsLp(a)PCSK9 |
| spellingShingle | Mohamed J. Nsaibia Anichavezhi Devendran Eshak Goubaa Jamal Bouitbir Romain Capoulade Rihab Bouchareb Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail? Journal of Clinical Medicine aortic valve lipids statins Lp(a) PCSK9 |
| title | Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail? |
| title_full | Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail? |
| title_fullStr | Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail? |
| title_full_unstemmed | Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail? |
| title_short | Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail? |
| title_sort | implication of lipids in calcified aortic valve pathogenesis why did statins fail |
| topic | aortic valve lipids statins Lp(a) PCSK9 |
| url | https://www.mdpi.com/2077-0383/11/12/3331 |
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