Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: Collagen accumulation in the young and loss in the aged

Horn, M; Graham, Helen K.; Richards, Mark; Clarke, Jessica D.; Greensmith, David J.; Briston, Sarah J.; Hall, Mark; Dibb, Katharine M.; Trafford, Andrew W.

doi:10.1016/j.yjmcc.2012.03.011

Cited by 87 publications

(75 citation statements)

References 41 publications

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“…3), although still great enough to maintain a higher E/A ratio in our SHAM mice, is likely the result of various LVage-related mechanisms. Past literature has postulated a reduction in calcium handling with SERCA2 ), increase in LV fibrosis and collagen accumulation (Emter and Baines 2010;Horn et al 2012), or mitochondrial damage due to reactive oxygen species (Dai and Rabinovitch 2009) as possible mediators of the agerelated decline in passive filling velocity.…”

Section: Discussionmentioning

confidence: 99%

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Turner

Guderian

Wikstrom

et al. 2016

AGE

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We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-toactive filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan.

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Section: Discussionmentioning

confidence: 99%

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Turner

Guderian

Wikstrom

et al. 2016

AGE

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“…In mouse models, Th2 induction resulted in reduced ventricular stiffness, and Th1 cells were involved in initiation of fibrosis and collagen crosslinking (Yu et al, 2005;, whereasanother 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 21 study did detecta shift from Th1 to Th2 response in old mice in association with interstitial myocardial fibrosis (Cieslik et al, 2011). We observed a reduction of all three immune modulatory markers (IL-2, IL-4,IFN-γ)with age in thefemale cats, which might be consistent with a generally reduced myocardial inflammatory response, as suggested by thereduced transcriptionof IL-1 and IL-6.Aupperle and co-authors (2011) observed reduced TIMP-2 expression in association with myocardial fibrosis in cats.In older sheep (> 8 years), rat and mouse models, higher myocardial MMP-2 and reduced TIMP-2 mRNA and protein expression, as well as cardiomyocyte hypertrophy and perivascular and interstitial fibrosis, imbalanced cardiac remodelling and impaired repair was observed (Kandalam et al, 2010;Wang et al, 2010;Horn et al, 2012;Givvimani et al, 2013). The age-associated reduced TIMP-2 and MMP-2 transcription in female and male cats, respectively,suggests therefore a pro-fibrotic potential and impaired repair of the female myocardium, and further supports a reactive male myocardium facilitating appropriate repair (Davis et al, 2007;Chen and Frangogiannis, 2010).…”

Section: Discussionmentioning

confidence: 99%

Age- and gender-dependent myocardial transcription patterns of cytokines and extracellular matrix remodelling enzymes in cats with non-cardiac diseases

Fonfara

Hetzel

Hahn

et al. 2015

Experimental Gerontology

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Background:Age, genderand systemic diseases all influence cardiac function and remodelling.In cats, age and genderassociated myocardial remodelling and the effect of systemic diseases on the myocardium have so far not been studied. The aim of the study was therefore to investigate whetherrelevant cytokines and extracellular matrix (ECM) remodellingenzymesare expressed in the myocardium of cats with non-cardiac diseasesand whether transcription levels are influenced by age and gender. Methods:The study was performed on myocardial samples from 26 cats aged between 2 and 19 years that had died with non-cardiac diseases. Seventeen cats were female (2 entire), nine were male (1 entire). Of these, nine cats were diagnosed with diseases unlikely to affect the myocardium (control cats). The remaining 17 cats suffered from diseases with likely systemic effects.All hearts were assessed for any pathological changes, and the myocardium was analysed for interleukin (IL)-1, -2, -4, -6, -18, tumour necrosis factor (TNF)-, interferon(IFN)-, transforming growth factor (TGF)-, matrix metalloproteinase (MMP)-2, -3, -13, tissue inhibitor of MMP (TIMP)-1, -2 and -3 transcription using quantitative RT-PCR assays. Results:Despite the absence of any histological evidence of myocardial damage,inflammation and fibrosis, the myocardium of all cats was found to constitutively transcribe cytokines and ECM remodelling enzymes, with generally higher mRNA concentrations in atria than in ventricles.Young and male cats exhibited higher transcription levels throughout the myocardium in comparison to older and female cats. Furthermore, age-associated transcription pattern differed between male and female cats. Conclusion:The constitutive transcription of ECM remodellingenzymes suggests continuous myocardial remodelling throughout the entire life of a cat. The myocardium of young and malecats appears to be in a pro-inflammatory state, whereas in older and female cats the myocardium exhibits a reduced inflammatory reaction to systemic disease.Age-associated cardiac remodelling seems to be influenced bynon-hormonal factors inmale and female cats. Abstract: Background: Age, gender and systemic diseases all influence cardiac function and remodelling. In cats, age and gender associated myocardial remodelling and the effect of systemic diseases on the myocardium have so far not been studied. The aim of the study was therefore to investigate whether relevant cytokines and extracellular matrix (ECM) remodelling enzymes are expressed in the myocardium of cats with non-cardiac diseases and whether transcription levels are influenced by age and gender. Methods: The study was performed on myocardial samples from 26 cats aged between 2 and 19 years that had died with non-cardiac diseases. Seventeen cats were female (2 entire), nine were male (1 entire). Of these, nine cats were diagnosed with diseases unlikely to affect the myocardium (control cats). The remaining 17 cats suffered from diseases with likely systemic effects. All hearts were assessed fo...

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“…In muscle, the collagen content of the LV increased with age in wild-type mice, 76 sheep, 77 and humans (independent of pathology), [78][79][80] This change in LV collagen concentration may result from a variety of molecular factors recently reviewed. 81 Additionally, older (20 months old) BALB/c mice had more LV hydroxyproline, collagen, fibronectin, a-1 integrin, and a-5 integrin, but less b-1 integrin, than young (2 months old) or middle-aged (12 months old) mice.…”

Section: Compositional Changes With Age and Potential Influence On Msmentioning

confidence: 99%

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

Lynch

Pei²

2014

Organogenesis

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A recent paper demonstrated that decellularized extracellular matrix (DECM) deposited by synovium-derived stem cells (SDSCs), especially from fetal donors, could rejuvenate human adult SDSCs in both proliferation and chondrogenic potential, in which expanded cells and corresponding culture substrate (such as DECM) were found to share a mutual reaction in both elasticity and protein profiles (see ref.

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Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: Collagen accumulation in the young and loss in the aged

Cited by 87 publications

References 41 publications

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Age- and gender-dependent myocardial transcription patterns of cytokines and extracellular matrix remodelling enzymes in cats with non-cardiac diseases

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

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