Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload
Summary: Activated factor X is a key component of the coagulation cascade, but whether it directly regulates pathological cardiac remodeling is unclear. In mice subjected to pressure overload stress, cardiac factor X mRNA expression and activity increased concurrently with cardiac hypertrophy, fibro...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | JACC: Basic to Translational Science |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X19303146 |
| _version_ | 1828367569950605312 |
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| author | Xinji Guo, PhD Mikhail A. Kolpakov, MD, PhD Bahman Hooshdaran, PhD William Schappell, BS Tao Wang, MD, PhD Satoru Eguchi, MD, PhD Katherine J. Elliott, PhD Douglas G. Tilley, PhD A. Koneti Rao, MD Patricia Andrade-Gordon, PhD Matthew Bunce, PhD Chintala Madhu, PhD Steven R. Houser, PhD Abdelkarim Sabri, PhD |
| author_facet | Xinji Guo, PhD Mikhail A. Kolpakov, MD, PhD Bahman Hooshdaran, PhD William Schappell, BS Tao Wang, MD, PhD Satoru Eguchi, MD, PhD Katherine J. Elliott, PhD Douglas G. Tilley, PhD A. Koneti Rao, MD Patricia Andrade-Gordon, PhD Matthew Bunce, PhD Chintala Madhu, PhD Steven R. Houser, PhD Abdelkarim Sabri, PhD |
| author_sort | Xinji Guo, PhD |
| collection | DOAJ |
| description | Summary: Activated factor X is a key component of the coagulation cascade, but whether it directly regulates pathological cardiac remodeling is unclear. In mice subjected to pressure overload stress, cardiac factor X mRNA expression and activity increased concurrently with cardiac hypertrophy, fibrosis, inflammation and diastolic dysfunction, and responses blocked with a low coagulation-independent dose of rivaroxaban. In vitro, neurohormone stressors increased activated factor X expression in both cardiac myocytes and fibroblasts, resulting in activated factor X-mediated activation of protease-activated receptors and pro-hypertrophic and -fibrotic responses, respectively. Thus, inhibition of cardiac-expressed activated factor X could provide an effective therapy for the prevention of adverse cardiac remodeling in hypertensive patients. Key Words: activated coagulation factor X, cardiac hypertrophy, coagulation, fibrosis, protease-activated receptors, rivaroxaban |
| first_indexed | 2024-04-14T05:59:31Z |
| format | Article |
| id | doaj.art-129e8e00131747649c682ca916df38a5 |
| institution | Directory Open Access Journal |
| issn | 2452-302X |
| language | English |
| last_indexed | 2024-04-14T05:59:31Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Basic to Translational Science |
| spelling | doaj.art-129e8e00131747649c682ca916df38a52022-12-22T02:08:48ZengElsevierJACC: Basic to Translational Science2452-302X2020-01-01516983Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure OverloadXinji Guo, PhD0Mikhail A. Kolpakov, MD, PhD1Bahman Hooshdaran, PhD2William Schappell, BS3Tao Wang, MD, PhD4Satoru Eguchi, MD, PhD5Katherine J. Elliott, PhD6Douglas G. Tilley, PhD7A. Koneti Rao, MD8Patricia Andrade-Gordon, PhD9Matthew Bunce, PhD10Chintala Madhu, PhD11Steven R. Houser, PhD12Abdelkarim Sabri, PhD13Cardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCenter of Translational Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaSol Sherry Thrombosis Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaJanssen Pharmaceutical, Spring House, PennsylvaniaJanssen Pharmaceutical, Spring House, PennsylvaniaJanssen Pharmaceutical, Spring House, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, PennsylvaniaCardiovascular Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania; Address for correspondence: Dr. Abdelkarim Sabri, Cardiovascular Research Center, Temple University, MERB 1045, 3500 North Broad Street, Philadelphia, Pennsylvania 19140.Summary: Activated factor X is a key component of the coagulation cascade, but whether it directly regulates pathological cardiac remodeling is unclear. In mice subjected to pressure overload stress, cardiac factor X mRNA expression and activity increased concurrently with cardiac hypertrophy, fibrosis, inflammation and diastolic dysfunction, and responses blocked with a low coagulation-independent dose of rivaroxaban. In vitro, neurohormone stressors increased activated factor X expression in both cardiac myocytes and fibroblasts, resulting in activated factor X-mediated activation of protease-activated receptors and pro-hypertrophic and -fibrotic responses, respectively. Thus, inhibition of cardiac-expressed activated factor X could provide an effective therapy for the prevention of adverse cardiac remodeling in hypertensive patients. Key Words: activated coagulation factor X, cardiac hypertrophy, coagulation, fibrosis, protease-activated receptors, rivaroxabanhttp://www.sciencedirect.com/science/article/pii/S2452302X19303146 |
| spellingShingle | Xinji Guo, PhD Mikhail A. Kolpakov, MD, PhD Bahman Hooshdaran, PhD William Schappell, BS Tao Wang, MD, PhD Satoru Eguchi, MD, PhD Katherine J. Elliott, PhD Douglas G. Tilley, PhD A. Koneti Rao, MD Patricia Andrade-Gordon, PhD Matthew Bunce, PhD Chintala Madhu, PhD Steven R. Houser, PhD Abdelkarim Sabri, PhD Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload JACC: Basic to Translational Science |
| title | Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload |
| title_full | Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload |
| title_fullStr | Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload |
| title_full_unstemmed | Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload |
| title_short | Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload |
| title_sort | cardiac expression of factor x mediates cardiac hypertrophy and fibrosis in pressure overload |
| url | http://www.sciencedirect.com/science/article/pii/S2452302X19303146 |
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