Paradoxical Roles of Perivascular Adipose Tissue in Atherosclerosis and Hypertension

Chang, Lin; Hamblin, Milton; Eitzman, Daniel T.; Chen, Y. Eugene

doi:10.1253/circj.cj-12-1393

Cited by 78 publications

(67 citation statements)

References 72 publications

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“…Moreover, the beneficial effect on glucose metabolism was also extended to humans: in healthy volunteers Chondronikola et al demonstrated that activated BAT increased insulin sensitivity [19]. In addition, perivascular and epicardial adipose tissue depots, which share characteristics of BAT [20], are implicated in the modulation of atherosclerosis and blood pressure [21]. …”

Section: Introductionmentioning

confidence: 99%

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Thoonen

Ernande

Cheng

et al. 2015

Journal of Molecular and Cellular Cardiology

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Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1 −/− ) mice, which have dysfunctional BAT, were subjected to catecholamineinduced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1 −/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1 −/− mice. UCP1 −/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1 −/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1 −/− BAT transplanted to either UCP1 −/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1 −/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1 −/− mice,

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Section: Introductionmentioning

confidence: 99%

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Thoonen

Ernande

Cheng

et al. 2015

Journal of Molecular and Cellular Cardiology

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“…Through both endocrine and paracrine functions, PVAT regulates vascular tone in both humans and rodents ( Figure 6). (Chang et al, 2013) Under normal physiological conditions, the balance between the pro-and anti-contractile activities of PVAT is essential for maintaining vascular homeostasis and normal blood pressure. PVAT exerts its anti-contractile effect via direct action on VSMCs through the activation of potassium channels (Lohn et al, 2002) and subsequent vasorelaxation.…”

Section: Involvement Of Perivascular Adipose Tissue In Vascular Inflamentioning

confidence: 99%

Targeting vascular remodeling in abdominal aortic aneurysm : To identify novel treatment strategies and drug candidates

Vorkapić¹

2016

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Abdominal aortic aneurysm (AAA) is a degenerative weakening of the aortic wall, mainly affecting elderly men with a prevalence of 4.4-7.7 %. AAA is characterized by medial and adventitial inflammatory cell infiltration associated with vascular remodeling of the extracellular matrix proteins such as collagen and elastin and with phenotypic modulation and loss of vascular smooth muscle cells (VSMCs). Although much research has been performed, the precise cellular and molecular pathways behind these processes are still poorly understood. The overall aim of this thesis was to target signaling pathways that affect vascular remodeling of AAA to potentially identify novel strategies and drug candidates for future treatment of aneurysmal diseases. In order to develop our understanding of the pathophysiology of AAA, we used the angiotensin (Ang) II-induced AAA animal model and human biopsies taken at end-stage of disease to recapitulate key aspects of disease formation.Innate immune receptors such as toll-like receptors (TLRs) are known to regulate immunological processes leading to the formation and progression of vascular disease including AAA. In paper I, we aimed to investigate the role of TLR signaling under the control of the TRIF adaptor protein in the formation of AAA. Human, aneurysmal aortas displayed increased expression of TLR3 and TLR4 in surface of macrophages and T lymphocytes. AngII-induced aneurysm formation was attenuated in mice lacking the Trif gene (ApoE −/− Trif −/− ), and these knockout mice presented with a more intact medial layer together with a reduced inflammatory response by macrophages and T lymphocytes and reduced levels of pro-inflammatory cytokines, chemokines, and proteases. Our results suggest an involvement of TRIF in the pathophysiology of AAA.Current management of AAA fully depends on imaging and surgical techniques, and drugbased therapies are still mostly ineffective. In paper II, we aimed to investigate the potential protective role of the tyrosine kinase inhibitor imatinib on the molecular mechanism involved in AAA formation. In AngII-infused ApoE −/− mice, 10 mg/kg imatinib per day affected several key features important in aneurysmal formation, including preservation of the medial layer of the VSMCs, reduced infiltration of CD3ε-positive T lymphocytes, and reduced gene expression of mast cell chymase, resulting in decreased aortic diameter and vessel wall thickness. These results highlight the importance of the tyrosine kinase inhibitor imatinib as a VI potential drug in the treatment of pathological vascular inflammation and remodeling in conditions such as AAA.In paper III, we aimed to investigate the role of adiponectin in experimentally induced AAA formation in mice. In mice with elevated adiponectin levels, AAA development was inhibited, and this was associated with reduced inflammatory cell infiltration, reduced medial degeneration of VSMCs and of elastin in the aortic vessel wall together with an improved systemic cytokine profile and the attenuation of periaorti...

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“…81,82 Such dysfunctional PVAT has been shown to constantly feature a typical immune cell infiltration, which is thought to be able to trigger inflammation and oxidative stress, possibly resulting in local hypoxic processes. 83 In this modified milieu, PVAT changes its physiologic secretion profile, decreasing the production of 'healthy' adipokines, such as adiponectin, and increasing the production of vascular endothelial grow factor (VEGF), hepatocyte growth factor (HGF), acidic fibroblast growth factor, monocyte chemoattractant protein 1 (MCP-1) and insulin-like growth factors, promoting vascular wall remodelling and possibly causing lesion instability and plaque rupture.…”

Section: The Discontinuation Of the Internal Elastic Laminamentioning

confidence: 99%

Localizing factors in atherosclerosis

Pescetelli

Zimarino

Ghirarduzzi

et al. 2015

Journal of Cardiovascular Medicine

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Atherosclerotic vascular disease is the leading cause of death worldwide. Although the entire vascular bed is constantly exposed to the same risk factors, atheromatous lesions present a distinct intra-individual pattern of localization and progression, being consistently more frequent in specific segments of the arterial vascular bed. This peculiar distribution may be related to selective sensitivity of such locations to the influence of risk factors or to histopathological and flow differences, and has relevant clinical implications, as the prognosis of the disease varies according to localization. We here review the theories that have been formulated to explain such preferential locations, as its understanding can be useful to pursue diagnostic screening strategies and focused preventive measures.

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Paradoxical Roles of Perivascular Adipose Tissue in Atherosclerosis and Hypertension

Cited by 78 publications

References 72 publications

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Targeting vascular remodeling in abdominal aortic aneurysm : To identify novel treatment strategies and drug candidates

Localizing factors in atherosclerosis

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