Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis

Drosos, Ioannis; Chalikias, Georgios K.; Pavlaki, Maria; Kareli, Dimitra; Epitropou, Grigorios; Bougioukas, Georgios; Mikroulis, Dimitrios; Konstantinou, Fotis; Giatromanolaki, Alexandra; Ritis, Konstantinos; Münzel, Thomas; Tziakas, Dimitrios; Konstantinides, Stavros; Schäfer, Katrin

doi:10.1007/s00392-016-0996-7

Cited by 51 publications

(42 citation statements)

References 58 publications

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“…Furthermore, it was well established that an inflammatory micro‐environment induced by trauma exert a key role in the development of HO (Bartlett et al, ; Rapuano et al, ; Schurch, Capaul, Vallotton, & Rossier, ). Although leptin has been considered as a vital pro‐inflammatory mediator (Drosos et al, ; Vuolteenaho et al, ), which may subsequently lead to pathogenesis and progression of HO due to its pro‐inflammatory effect, its function and action mechanism in HO of tendon tissues have been unclear. Our study demonstrated that leptin promoted osteogenic differentiation of TDSCs in vitro and in vivo, which contributed to the accelerated heterotopic formation in the rat model.…”

Section: Discussionmentioning

confidence: 99%

Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling

Jiang¹,

Chen²,

Chen³

et al. 2017

Journal Cellular Physiology

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Leptin, an adipocyte-derived cytokine associated with bone metabolism, is believed to play a critical role in the pathogenesis of heterotopic ossification (HO). The effect and underlying action mechanism of leptin were investigated on osteogenic differentiation of tendon-derived stem cells (TDSCs) in vitro and the HO formation in rat tendons. Isolated rat TDSCs were treated with various concentrations of leptin in the presence or absence of mTORC1 signaling specific inhibitor rapamycin in vitro. A rat model with Achilles tenotomy was employed to evaluate the effect of leptin on HO formation together with or without rapamycin treatment. In vitro studies with TDSCs showed that leptin increased the expression of osteogenic biomarkers (alkaline phosphatase, runt-related transcription factor 2, osterix, osteocalcin) and enhanced mineralization of TDSCs via activating the mTORC1 signal pathway (as indicated by phosphorylation of p70 ribosomal S6 kinase 1 and p70 ribosomal S6). However, mTORC1 signaling blockade with rapamycin treatment suppressed leptin-induced osteogenic differentiation and mineralization. In vivo studies showed that leptin promoted HO formation in the Achilles tendon after tenotomy, and rapamycin treatment blocked leptin-induced HO formation. In conclusion, leptin can promote TDSC osteogenic differentiation and heterotopic bone formation via mTORC1 signaling in both vitro and vivo model, which provides a new potential therapeutic target for HO prevention.

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Section: Discussionmentioning

confidence: 99%

Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling

Jiang¹,

Chen²,

Chen³

et al. 2017

Journal Cellular Physiology

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“…PVAT of the murine thoracic aorta) or mixed adipose tissue (e.g. PVAT of the murine abdominal aorta) and may have different vascularization, innervation and adipokine profiles (Szasz and Webb, ; Padilla et al, ; Brown et al, ; Gil‐Ortega et al, ; Drosos et al, ; Victorio et al, ).…”

Section: Pvat: General Aspectsmentioning

confidence: 99%

The role of perivascular adipose tissue in obesity‐induced vascular dysfunction

Xia

2016

British J Pharmacology

162

152

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Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist‐induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1–7, adiponectin, methyl palmitate, hydrogen sulfide, NO and leptin. This anticontractile effect of PVAT is lost under conditions of obesity. The central mechanism underlying this PVAT dysfunction in obesity is likely to be an ‘obesity triad’ (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to the impairment of PVAT‐derived vasoregulators. The production of hydrogen sulfide, NO and adiponectin by PVAT is reduced in obesity, whereas the vasodilator response to leptin is impaired (vascular leptin resistance). Strikingly, the vasodilator response to acetylcholine is reduced only in PVAT‐containing, but not in PVAT‐free thoracic aorta isolated from diet‐induced obese mice, indicating a unique role for PVAT in obesity‐induced vascular dysfunction. Furthermore, PVAT dysfunction has also been observed in small arteries isolated from the gluteal/visceral fat biopsy samples of obese individuals. Therefore, PVAT may represent a new therapeutic target for vascular complications in obesity. A number of approaches are currently being tested under experimental conditions. Potential therapeutic strategies improving PVAT function include body weight reduction, enhancing PVAT hydrogen sulfide release (e.g. rosiglitazone, atorvastatin and cannabinoid CB1 receptor agonists) and NO production (e.g. arginase inhibitors), inhibition of the renin–angiotensin–aldosterone system, inhibition of inflammation with melatonin or cytokine antagonists, activators of AMP‐activated kinase (e.g. metformin, resveratrol and diosgenin) and adiponectin releasers or expression enhancers.Linked ArticlesThis article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc

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“…In addition, patients with abdominal aortic aneurysms had local necrotic and highly inflamed PVAT compared to PVAT surrounding aortae from patients without vascular disease[45]. One study compared PVAT surrounding the heart (atherosusceptible) and PVAT surrounding the internal mammary artery (atheroresistant) in males undergoing coronary artery bypass grafting (CABG) surgery for advanced atherosclerotic disease[46]. That study showed that leptin levels were lower in PVAT from the internal mammary artery compared to PVAT surrounding the aortic root and coronary arteries.…”

Section: Discussionmentioning

confidence: 99%

Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation

Boucher

Robich

Scott

et al. 2018

Cardiovasc Drugs Ther

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Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis

Abstract: A higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

Cited by 51 publications

References 58 publications

Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling

Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling

The role of perivascular adipose tissue in obesity‐induced vascular dysfunction

Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation

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