Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production

Sawaki, Daigo; Czibik, Gabor; Pini, Maria Silvia; Ternacle, Julien; Suffee, Nadine; Mercedes, Raquel; Marcelin, Geneviève; Surénaud, Mathieu; Marcos, Élisabeth; Gual, Philippe; Clément, Karine; Hüe, Sophie; Adnot, Serge; Hatem, Stéphane; Tsuchimochi, Izuru; Yoshimitsu, Takehiko; Hénégar, Corneliu; Dérumeaux, Geneviève

doi:10.1161/circulationaha.117.031358

Cited by 128 publications

(108 citation statements)

References 50 publications

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“…Transthoracic echocardiography. Transthoracic echocardiography was performed in conscious mice as previously described (43,44). Briefly, in hand-gripped mouse parasternal images were acquired at the level of papillary muscles using a 13-MHz linear-array transducer with a Vivid 7 ultrasound system (GE Medical System).…”

Section: Methodsmentioning

confidence: 99%

“…Left ventricular dimensions were serially obtained in M-mode, and derived parameters were calculated using standard formulas. Left ventricular mass was determined using the uncorrected cube assumption (43,44). Peak systolic values of strain rate in the anterior and posterior wall were obtained using Tissue Doppler Imaging.…”

Section: Methodsmentioning

confidence: 99%

“…Strain rate analysis with EchoPac Software (GE Medical System) was performed offline by a blinded observer. Peak systolic strain rate on 8 consecutive cardiac cycles were averaged to reduce the effect of respiratory variations (43,44).…”

Section: Methodsmentioning

confidence: 99%

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Carbon monoxide–induced metabolic switch in adipocytes improves insulin resistance in obese mice

Braud¹,

Pini²,

Muchová³

et al. 2018

JCI Insight

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Carbon monoxide–induced metabolic switch in adipocytes improves insulin resistance in obese mice

Braud¹,

Pini²,

Muchová³

et al. 2018

JCI Insight

Self Cite

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“…Such systemic effects are currently being studied in the European BETA3-LVH trial testing the re-purposing of mirabegron in patients with structural cardiac remodelling with or at risk of developing heart failure with preserved ejection fraction 35 . Further, β3-AR modulation of visceral adipose tissue may have remote effects on cardiac aging by regulating fibroblast senescence 36 , although this has not been directly demonstrated so far.…”

Section: Discussionmentioning

confidence: 94%

Beta-3 Adrenoreceptors protect from hypertrophic remodelling through AMP-Activated Protein Kinase and Autophagy

Dubois‐Deruy

Gélinas

Beauloye

et al. 2020

Preprint

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Aims: The abundance of beta3-adrenergic receptors (β3-ARs) is upregulated in diseased human myocardium. We previously showed that cardiac-specific expression of β3-AR inhibits the hypertrophic response to neurohormonal stimulation. Here, we further analyzed signalling pathways involved in the anti-hypertrophic effect of β3-AR.Methods : In vitro hypertrophic responses to phenylephrine (PE) were analyzed in neonatal rat ventricular myocytes (NRVM) infected with a recombinant adenovirus expressing the human β3-AR (AdVhβ3). We confirmed results in mice with cardiomyocyte-specific moderate expression of human β3-AR (β3-TG) and WT littermates submitted to thoracic transverse aortic constriction (TAC) for 9 weeks.Results: We observed a colocalization of β3-AR with the AMP-activated protein kinase (AMPK) both in neonatal rat andin adult mouse cardiomyocytes. Treatment of NRVM with PE induced hypertrophy and a decrease in phosphorylation of Thr172-AMPK (/2, p=0.0487) and phosphorylation of Ser79-acetyl-CoA carboxylase (ACC) (/2.6, p=0.0317), inducing an increase in phosphorylated Ser235/236 S6 protein (x2.5, p=0.0367) known to be involved in protein synthesis. These effects were reproduced by TAC in WT mice, but restored to basal levels in β3-AR expressing cells/mice. siRNA targeting of AMPK partly abrogated the anti-hypertrophic effect of β3-AR in response to PE in NRVM (x1.3, p<0.0001). Concomitant with hypertrophy, autophagy measured by microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I ratio and p62 abundance was decreased by PE in NRVM (/2.6, p=0.0010 and x3, p=0.0016, respectively) or TAC in WT mice (/5.4, p=0.0159); and preserved in human β3-AR expressing cells and mice, together with reduced hypertrophy.Conclusions: Cardiac-specific moderate expression of β3-AR inhibits the hypertrophic response in part through AMPK activation followed byinhibition of protein synthesis and preservation of autophagy.Activation of the cardiac β3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodelling.

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“…Moreover, OPN knockdown has been shown to reduce senile cardiac fibrosis by inducing senescence of myofibroblasts (Sawaki et al, 2018). Therefore, a large amount of research is required to explore the effect of induced cell senescence on fibrosis in elderly or chronic diseases.…”

Section: Effect Of Myofibroblast Senescence On Lung Fibrosismentioning

confidence: 99%

The potential role of senescence in limiting fibrosis caused by aging

Meng

Wang

Song

et al. 2019

Journal Cellular Physiology

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Fibrosis-related diseases carry with them a high mortality rate and their morbidity increases with age. Recent findings indicate that induced senescence in myofibroblasts can limit or reduce myocardial fibrosis, cirrhosis, and idiopathic pulmonary fibrosis, while also accelerating wound healing. However, more senescent cells are accumulated as organisms age, which exacerbates aging-related diseases. These two contradictory theories inspired us to summarize papers on the restrictive effect of senescence on fibrosis and to input the key findings into simple software that we developed to assist with data organization and presentation. In this review, we illustrate that senescent cells secrete more matrix metalloproteinases to solubilize excess collagen, while chemokines and cytokines activate immune cells to eliminate senescent cells. In the elderly, it is perhaps more effective to limit fibrosis by inducing myofibroblast senescence and then removing senescent cells that are not cleared via normal mechanisms by antisenescence therapies.

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Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production

Cited by 128 publications

References 50 publications

Carbon monoxide–induced metabolic switch in adipocytes improves insulin resistance in obese mice

Carbon monoxide–induced metabolic switch in adipocytes improves insulin resistance in obese mice

Beta-3 Adrenoreceptors protect from hypertrophic remodelling through AMP-Activated Protein Kinase and Autophagy

The potential role of senescence in limiting fibrosis caused by aging

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