- Title
- Aging is protective against pressure overload cardiomyopathy via adaptive extracellular matrix remodeling
- Creator
- Geng, Xiaoyong; Hwang, Joy; Boyle, Andrew J.; Ye, Jianqin; Shih, Henry; Coulter, Brianna; Naudin, Crystal; Jun, Kristine; Sievers, Richard; Yeghiazarians, Yerem; Lee, Randall J.
- Relation
- American Journal of Cardiovascular Disease Vol. 7, Issue 3, p. 72-82
- Relation
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498818/
- Publisher
- E-Century Publishing
- Resource Type
- journal article
- Date
- 2017
- Description
- When challenged by hemodynamic stress, aging hearts respond differently to young hearts. Preclinical models of heart disease should take into account the effects of age. However, in the transverse aortic constriction (TAC) model of pressure-overload cardiomyopathy, the larger aorta of aging mice has not previously been taken into account. First, we studied the aortic size in mice, and found that the aortic cross-sectional area (CSA) is 28% larger in aging mice than in young adult mice (P=0.001). We then performed TAC to make the same proportional reduction in CSA in young and aging mice. This produced the same pressure gradient across the constriction and the same rise in B-type natriuretic peptide expression. Young mice showed acute deterioration in systolic function assessed by pressure-volume loops, progressive LV remodeling on echocardiography, and a 50% mortality at 12 weeks post-TAC. In contrast, aging mice showed no acute deterioration in systolic function, much less ventricular remodeling and were protected from death. Aging mice also showed significantly increased levels of matrix metalloproteinase-3 (MMP-3; 3.2 fold increase, P<0.001) and MMP-12 (1.5-fold increase, P<0.001), which were not seen in young mice. Expression of tissue inhibitor of MMP-1 (TIMP-1) increased 8.6-fold in aging hearts vs 4.3-fold in young hearts (P<0.01). In conclusion, following size-appropriate TAC, aging mice exhibit less LV remodeling and lower mortality than young adult mice. This is associated with induction of protective ECM changes.
- Subject
- aging; heart failure; pressure overload; cardiac fibrosis
- Identifier
- http://hdl.handle.net/1959.13/1397274
- Identifier
- uon:34229
- Identifier
- ISSN:2160-200X
- Rights
- © 2017 Published under the “Creative Commons Attribution Noncommercial License”, enabling the unrestricted non-commercial use, distribution, and reproduction of the published article in any medium, provided that the original work is properly cited.
- Language
- eng
- Full Text
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