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HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype
Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine single nucleotide polymorphisms (SNPs) associated with the extent of abdominal (AAC, n = 9,417) or descending thoracic (TAC, n = 8,422) aortic...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2019
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858575/ https://www.ncbi.nlm.nih.gov/pubmed/31659325 http://dx.doi.org/10.1038/s41588-019-0514-8 |
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| author | Malhotra, Rajeev Mauer, Andreas C. Cardenas, Christian L. Lino Guo, Xiuqing Yao, Jie Zhang, Xiaoling Wunderer, Florian Smith, Albert V. Wong, Quenna Pechlivanis, Sonali Hwang, Shih-Jen Wang, Judy Lu, Lingyi Nicholson, Christopher J. Shelton, Georgia Buswell, Mary D. Barnes, Hanna J. Sigurslid, Haakon H. Slocum, Charles O’Rourke, Caitlin Rhee, David K. Bagchi, Aranya Nigwekar, Sagar U. Buys, Emmanuel S. Campbell, Catherine Y. Harris, Tamara Budoff, Matthew Criqui, Michael H. Rotter, Jerome I. Johnson, Andrew D. Song, Ci Franceschini, Nora Debette, Stephanie Hoffmann, Udo Kälsch, Hagen Nöthen, Markus M. Sigurdsson, Sigurdur Freedman, Barry I. Bowden, Donald W. Jöckel, Karl-Heinz Moebus, Susanne Erbel, Raimund Feitosa, Mary F. Gudnason, Vilmundur Thanassoulis, George Zapol, Warren M. Lindsay, Mark E. Bloch, Donald B. Post, Wendy S. O’Donnell, Christopher J. |
| author_facet | Malhotra, Rajeev Mauer, Andreas C. Cardenas, Christian L. Lino Guo, Xiuqing Yao, Jie Zhang, Xiaoling Wunderer, Florian Smith, Albert V. Wong, Quenna Pechlivanis, Sonali Hwang, Shih-Jen Wang, Judy Lu, Lingyi Nicholson, Christopher J. Shelton, Georgia Buswell, Mary D. Barnes, Hanna J. Sigurslid, Haakon H. Slocum, Charles O’Rourke, Caitlin Rhee, David K. Bagchi, Aranya Nigwekar, Sagar U. Buys, Emmanuel S. Campbell, Catherine Y. Harris, Tamara Budoff, Matthew Criqui, Michael H. Rotter, Jerome I. Johnson, Andrew D. Song, Ci Franceschini, Nora Debette, Stephanie Hoffmann, Udo Kälsch, Hagen Nöthen, Markus M. Sigurdsson, Sigurdur Freedman, Barry I. Bowden, Donald W. Jöckel, Karl-Heinz Moebus, Susanne Erbel, Raimund Feitosa, Mary F. Gudnason, Vilmundur Thanassoulis, George Zapol, Warren M. Lindsay, Mark E. Bloch, Donald B. Post, Wendy S. O’Donnell, Christopher J. |
| author_sort | Malhotra, Rajeev |
| collection | PubMed |
| description | Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine single nucleotide polymorphisms (SNPs) associated with the extent of abdominal (AAC, n = 9,417) or descending thoracic (TAC, n = 8,422) aortic calcification. Two genetic loci, HDAC9 and RAP1GAP, were associated with AAC at a genome-wide level (P < 5.0 × 10(−8)). No SNPs were associated with TAC at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells (HASMCs) promoted calcification and reduced contractility, while inhibition of HDAC9 in HASMCs inhibited calcification and enhanced cell contractility. In matrix Gla protein (MGP)-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a novel role for HDAC9 in the development of vascular calcification. |
| format | Online Article Text |
| id | pubmed-6858575 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-68585752020-04-28 HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype Malhotra, Rajeev Mauer, Andreas C. Cardenas, Christian L. Lino Guo, Xiuqing Yao, Jie Zhang, Xiaoling Wunderer, Florian Smith, Albert V. Wong, Quenna Pechlivanis, Sonali Hwang, Shih-Jen Wang, Judy Lu, Lingyi Nicholson, Christopher J. Shelton, Georgia Buswell, Mary D. Barnes, Hanna J. Sigurslid, Haakon H. Slocum, Charles O’Rourke, Caitlin Rhee, David K. Bagchi, Aranya Nigwekar, Sagar U. Buys, Emmanuel S. Campbell, Catherine Y. Harris, Tamara Budoff, Matthew Criqui, Michael H. Rotter, Jerome I. Johnson, Andrew D. Song, Ci Franceschini, Nora Debette, Stephanie Hoffmann, Udo Kälsch, Hagen Nöthen, Markus M. Sigurdsson, Sigurdur Freedman, Barry I. Bowden, Donald W. Jöckel, Karl-Heinz Moebus, Susanne Erbel, Raimund Feitosa, Mary F. Gudnason, Vilmundur Thanassoulis, George Zapol, Warren M. Lindsay, Mark E. Bloch, Donald B. Post, Wendy S. O’Donnell, Christopher J. Nat Genet Article Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine single nucleotide polymorphisms (SNPs) associated with the extent of abdominal (AAC, n = 9,417) or descending thoracic (TAC, n = 8,422) aortic calcification. Two genetic loci, HDAC9 and RAP1GAP, were associated with AAC at a genome-wide level (P < 5.0 × 10(−8)). No SNPs were associated with TAC at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells (HASMCs) promoted calcification and reduced contractility, while inhibition of HDAC9 in HASMCs inhibited calcification and enhanced cell contractility. In matrix Gla protein (MGP)-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a novel role for HDAC9 in the development of vascular calcification. 2019-10-28 2019-11 /pmc/articles/PMC6858575/ /pubmed/31659325 http://dx.doi.org/10.1038/s41588-019-0514-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Malhotra, Rajeev Mauer, Andreas C. Cardenas, Christian L. Lino Guo, Xiuqing Yao, Jie Zhang, Xiaoling Wunderer, Florian Smith, Albert V. Wong, Quenna Pechlivanis, Sonali Hwang, Shih-Jen Wang, Judy Lu, Lingyi Nicholson, Christopher J. Shelton, Georgia Buswell, Mary D. Barnes, Hanna J. Sigurslid, Haakon H. Slocum, Charles O’Rourke, Caitlin Rhee, David K. Bagchi, Aranya Nigwekar, Sagar U. Buys, Emmanuel S. Campbell, Catherine Y. Harris, Tamara Budoff, Matthew Criqui, Michael H. Rotter, Jerome I. Johnson, Andrew D. Song, Ci Franceschini, Nora Debette, Stephanie Hoffmann, Udo Kälsch, Hagen Nöthen, Markus M. Sigurdsson, Sigurdur Freedman, Barry I. Bowden, Donald W. Jöckel, Karl-Heinz Moebus, Susanne Erbel, Raimund Feitosa, Mary F. Gudnason, Vilmundur Thanassoulis, George Zapol, Warren M. Lindsay, Mark E. Bloch, Donald B. Post, Wendy S. O’Donnell, Christopher J. HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| title | HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| title_full | HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| title_fullStr | HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| title_full_unstemmed | HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| title_short | HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| title_sort | hdac9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858575/ https://www.ncbi.nlm.nih.gov/pubmed/31659325 http://dx.doi.org/10.1038/s41588-019-0514-8 |
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