PMID- 28695053
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2160-200X (Print)
IS  - 2160-200X (Electronic)
IS  - 2160-200X (Linking)
VI  - 7
IP  - 3
DP  - 2017
TI  - Aging is protective against pressure overload cardiomyopathy via adaptive 
      extracellular matrix remodeling.
PG  - 72-82
AB  - 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.
FAU - Geng, Xiaoyong
AU  - Geng X
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
AD  - Department of Cardiology, The Third Hospital of Hebei Medical UniversityChina.
FAU - Hwang, Joy
AU  - Hwang J
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
FAU - Ye, Jianqin
AU  - Ye J
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
AD  - Edyth and Eli Broad Center for Regenerative Medicine and Stem Cell ResearchUSA.
FAU - Shih, Henry
AU  - Shih H
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
FAU - Coulter, Brianna
AU  - Coulter B
AD  - Faculty of Health and Medicine, University of NewcastleAustralia.
FAU - Naudin, Crystal
AU  - Naudin C
AD  - Cardiovascular Research Institute, University of California San FranciscoSan 
      Francisco, CA, USA.
FAU - Jun, Kristine
AU  - Jun K
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
FAU - Sievers, Richard
AU  - Sievers R
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
FAU - Yeghiazarians, Yerem
AU  - Yeghiazarians Y
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
AD  - Edyth and Eli Broad Center for Regenerative Medicine and Stem Cell ResearchUSA.
FAU - Lee, Randall J
AU  - Lee RJ
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
AD  - Edyth and Eli Broad Center for Regenerative Medicine and Stem Cell ResearchUSA.
AD  - Cardiovascular Research Institute, University of California San FranciscoSan 
      Francisco, CA, USA.
FAU - Boyle, Andrew J
AU  - Boyle AJ
AD  - Department of Medicine, Division of Cardiology, University of California San 
      FranciscoSan Francisco, CA, USA.
AD  - Edyth and Eli Broad Center for Regenerative Medicine and Stem Cell ResearchUSA.
AD  - Faculty of Health and Medicine, University of NewcastleAustralia.
AD  - Hunter Medical Research InstituteNewcastle, Australia.
AD  - Department of Cardiovascular Medicine, John Hunter HospitalNewcastle, Australia.
LA  - eng
GR  - UL1 TR000004/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20170615
PL  - United States
TA  - Am J Cardiovasc Dis
JT  - American journal of cardiovascular disease
JID - 101569582
PMC - PMC5498818
OTO - NOTNLM
OT  - Aging
OT  - cardiac fibrosis
OT  - heart failure
OT  - pressure overload
COIS- None.
EDAT- 2017/07/12 06:00
MHDA- 2017/07/12 06:01
PMCR- 2017/06/15
CRDT- 2017/07/12 06:00
PHST- 2017/01/10 00:00 [received]
PHST- 2017/04/09 00:00 [accepted]
PHST- 2017/07/12 06:00 [entrez]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2017/07/12 06:01 [medline]
PHST- 2017/06/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cardiovasc Dis. 2017 Jun 15;7(3):72-82. eCollection 2017.