Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis
Calcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America. Despite the large burden of disease, there are no medical treatments to slow the development of AS, due at least in part to our incomplete understand...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520351713 |
| _version_ | 1818417716420149248 |
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| author | George Thanassoulis |
| author_facet | George Thanassoulis |
| author_sort | George Thanassoulis |
| collection | DOAJ |
| description | Calcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America. Despite the large burden of disease, there are no medical treatments to slow the development of AS, due at least in part to our incomplete understanding of its causes. The Cohorts for Heart and Aging Research in Genetic Epidemiology extra-coronary calcium consortium reported a genome-wide association study demonstrating that genetic variants in LPA are strongly associated with aortic valve (AV) calcium and clinical AS. Using a Mendelian randomization study design, it was demonstrated that the effect of this genetic variant is mediated by plasma lipoprotein (a) [Lp(a)], directly implicating elevations in Lp(a) as a cause of AV calcium and progression to AS. This discovery has sparked intense interest in Lp(a) as a modifiable cause for AV disease. Herein, we will review the mounting epidemiological and genetic findings in support of Lp(a)-mediated valve disease, discuss potential mechanisms underlying this observation, and outline the steps to translate this discovery to a much needed novel preventive and/or therapeutic strategy for AV disease. |
| first_indexed | 2024-12-14T12:11:12Z |
| format | Article |
| id | doaj.art-dcfaeb35f346468499fb19e5bcde7640 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T12:11:12Z |
| publishDate | 2016-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-dcfaeb35f346468499fb19e5bcde76402022-12-21T23:01:43ZengElsevierJournal of Lipid Research0022-22752016-06-01576917924Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosisGeorge Thanassoulis0To whom correspondence should be addressed; To whom correspondence should be addressed; Preventive and Genomic Cardiology, McGill University Health Center and Research Institute and Department of Medicine, McGill University, Montreal, QC, CanadaCalcific aortic stenosis (AS) is the most common form of valve disease in the Western world and affects over 2.5 million individuals in North America. Despite the large burden of disease, there are no medical treatments to slow the development of AS, due at least in part to our incomplete understanding of its causes. The Cohorts for Heart and Aging Research in Genetic Epidemiology extra-coronary calcium consortium reported a genome-wide association study demonstrating that genetic variants in LPA are strongly associated with aortic valve (AV) calcium and clinical AS. Using a Mendelian randomization study design, it was demonstrated that the effect of this genetic variant is mediated by plasma lipoprotein (a) [Lp(a)], directly implicating elevations in Lp(a) as a cause of AV calcium and progression to AS. This discovery has sparked intense interest in Lp(a) as a modifiable cause for AV disease. Herein, we will review the mounting epidemiological and genetic findings in support of Lp(a)-mediated valve disease, discuss potential mechanisms underlying this observation, and outline the steps to translate this discovery to a much needed novel preventive and/or therapeutic strategy for AV disease.http://www.sciencedirect.com/science/article/pii/S0022227520351713calciumdrug therapy/hypolipidemic drugslipoproteinsoxidized lipidsmendelian randomization |
| spellingShingle | George Thanassoulis Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis Journal of Lipid Research calcium drug therapy/hypolipidemic drugs lipoproteins oxidized lipids mendelian randomization |
| title | Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis |
| title_full | Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis |
| title_fullStr | Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis |
| title_full_unstemmed | Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis |
| title_short | Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis |
| title_sort | lipoprotein a in calcific aortic valve disease from genomics to novel drug target for aortic stenosis |
| topic | calcium drug therapy/hypolipidemic drugs lipoproteins oxidized lipids mendelian randomization |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520351713 |
| work_keys_str_mv | AT georgethanassoulis lipoproteinaincalcificaorticvalvediseasefromgenomicstonoveldrugtargetforaorticstenosis |