Title |
Cardiovascular Protection by ApoE and ApoE-HDL Linked to Suppression of ECM Gene Expression and Arterial Stiffening
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Published in |
Cell Reports, October 2012
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DOI | 10.1016/j.celrep.2012.09.018 |
Pubmed ID | |
Authors |
Devashish Kothapalli, Shu-Lin Liu, Yong Ho Bae, James Monslow, Tina Xu, Elizabeth A. Hawthorne, Fitzroy J. Byfield, Paola Castagnino, Shilpa Rao, Daniel J. Rader, Ellen Puré, Michael C. Phillips, Sissel Lund-Katz, Paul A. Janmey, Richard K. Assoian |
Abstract |
Arterial stiffening is a risk factor for cardiovascular disease, but how arteries stay supple is unknown. Here, we show that apolipoprotein E (apoE) and apoE-containing high-density lipoprotein (apoE-HDL) maintain arterial elasticity by suppressing the expression of extracellular matrix genes. ApoE interrupts a mechanically driven feed-forward loop that increases the expression of collagen-I, fibronectin, and lysyl oxidase in response to substratum stiffening. These effects are independent of the apoE lipid-binding domain and transduced by Cox2 and miR-145. Arterial stiffness is increased in apoE null mice. This stiffening can be reduced by administration of the lysyl oxidase inhibitor BAPN, and BAPN treatment attenuates atherosclerosis despite highly elevated cholesterol. Macrophage abundance in lesions is reduced by BAPN in vivo, and monocyte/macrophage adhesion is reduced by substratum softening in vitro. We conclude that apoE and apoE-containing HDL promote healthy arterial biomechanics and that this confers protection from cardiovascular disease independent of the established apoE-HDL effect on cholesterol. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 2% |
Netherlands | 1 | <1% |
Canada | 1 | <1% |
Unknown | 141 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 36 | 25% |
Researcher | 31 | 21% |
Student > Doctoral Student | 13 | 9% |
Student > Master | 12 | 8% |
Professor | 8 | 5% |
Other | 26 | 18% |
Unknown | 20 | 14% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 29 | 20% |
Agricultural and Biological Sciences | 29 | 20% |
Medicine and Dentistry | 25 | 17% |
Engineering | 18 | 12% |
Neuroscience | 4 | 3% |
Other | 12 | 8% |
Unknown | 29 | 20% |