Investigation of thrombospondin-1 and transforming growth factor-β expression in the heart of aging mice

Cai, Huacong; Yuan, Zhanggen; Fei, Qing; Zhao, Junjun

doi:10.3892/etm.2011.426

Cited by 23 publications

(20 citation statements)

References 19 publications

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“…Whilst inflammatory cytokines reduced with age, TGF-β transcriptionincreasedsuggestinga profibrotic potential of the myocardium. In mouse models of ageing, increased TGF-β protein expression was seen in association with interstitial myocardial fibrosis and decreased ventricular compliance (Brooks and Conrad, 2000;Wang et al, 2010;Cai et al, 2012), andin cardiac diseases, TGF-β is known to be involved in the pathogenesis of cardiac remodelling and fibrosis (Khan and Sheppard, 2006;Dobaczewski et al, 2011).…”

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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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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“…Levels of TSPs increase in multiple tissues with age (21, 116, 179-182). The significance of this increase in TSPs production is still unclear, although in some tissues it appears to be beneficial (21, 26, 179, 180).…”

Section: Introductionmentioning

confidence: 99%

“…The significance of this increase in TSPs production is still unclear, although in some tissues it appears to be beneficial (21, 26, 179, 180). In others, TSPs are associated with aging-related pathological changes (27, 116, 182, 183). …”

Section: Introductionmentioning

confidence: 99%

Invoking the power of thrombospondins: Regulation of thrombospondins expression

Stenina‐Adognravi¹

2014

Matrix Biology

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Increasing evidence suggests critical functions of thrombospondins (TSPs) in a variety of physiological and pathological processes. With the growing understanding of the importance of these matricellular proteins, the need to understand the mechanisms of regulation of their expression and potential approaches to modulate their levels is also increasing. The regulation of TSPs expression is multi-leveled, cell- and tissue-specific, and very precise. However, the knowledge of mechanisms modulating the levels of TSPs is fragmented and incomplete. This review discusses the known mechanisms of regulation of TSPs levels and the gaps in our knowledge that prevent us from developing strategies to modulate the expression of these physiologically important proteins.

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“…2 TGF-b has been reported to increase in the myocardium during aging, although why this occurs remains poorly understood. 43,44 We observed an increase in TGF-b signaling in the myocardium as early as 40 weeks. In addition to this increase in TGF-b, we also report here for the first time an age-related increase in the production of the downstream mediator CTGF.…”

Section: Discussionmentioning

confidence: 85%

Disruption of Collagen Homeostasis Can Reverse Established Age-Related Myocardial Fibrosis

Rosin

Sopel

Falkenham

et al. 2015

The American Journal of Pathology

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Heart failure, the leading cause of hospitalization of elderly patients, is correlated with myocardial fibrosis (ie, deposition of excess extracellular matrix proteins such as collagen). A key regulator of collagen homeostasis is lysyl oxidase (LOX), an enzyme responsible for cross-linking collagen fibers. Our objective was to ameliorate age-related myocardial fibrosis by disrupting collagen cross-linking through inhibition of LOX. The nonreversible LOX inhibitor β-aminopropionitrile (BAPN) was administered by osmotic minipump to 38-week-old C57BL/6J male mice for 2 weeks. Sirius Red staining of myocardial cross sections revealed a reduction in fibrosis, compared with age-matched controls (5.84 ± 0.30% versus 10.17 ± 1.34%) (P < 0.05), to a level similar to that of young mice at 8 weeks (4.9 ± 1.2%). BAPN significantly reduced COL1A1 mRNA, compared with age-matched mice (3.5 ± 0.3-fold versus 15.2 ± 4.9-fold) (P < 0.05), suggesting that LOX is involved in regulation of collagen synthesis. In accord, fibrotic factor mRNA expression was reduced after BAPN. There was also a novel increase in Ly6C expression by resident macrophages. By interrupting collagen cross-linking by LOX, the BAPN treatment reduced myocardial fibrosis. A novel observation is that BAPN treatment modulated the transforming growth factor-β pathway, collagen synthesis, and the resident macrophage population. This is especially valuable in terms of potential therapeutic targeting of collagen regulation and thereby age-related myocardial fibrosis.

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Investigation of thrombospondin-1 and transforming growth factor-β expression in the heart of aging mice

Cited by 23 publications

References 19 publications

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

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

Invoking the power of thrombospondins: Regulation of thrombospondins expression

Disruption of Collagen Homeostasis Can Reverse Established Age-Related Myocardial Fibrosis

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