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Maik Gollasch - One of the best experts on this subject based on the ideXlab platform.

  • Aging affects KV7 channels and Perivascular-Adipose Tissue-mediated vascular tone
    2021
    Co-Authors: Yibin Wang, Fatima Yildiz, Andrey Struve, Mario Kassmann, Friedrich C. Luft, Maik Gollasch, Dmitry Tsvetkov
    Abstract:

    AbstractAging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of Perivascular Adipose Tissue and downstream vasoconstriction targets, voltage-dependent KV7 channels, and their pharmacological modulators (flupirtine, retigabine, QO58, QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteries in vitro using wire myography. We also performed bulk RNA sequencing and quantitative reverse transcription polymerase chain reaction tests in mesenteric arteries and Perivascular Adipose Tissue to elucidate molecular underpinnings of age-related phenotypes. Results revealed impaired Perivascular Adipose Tissue-mediated control of vascular tone particularly via KV7.3-5 channels with increased age through metabolic and inflammatory processes and release of Perivascular Adipose Tissue-derived relaxation factors. Moreover, QO58 was identified as novel pharmacological vasodilator to activate XE991-sensitive KCNQ channels in old mesenteric arteries. Our data suggest that targeting inflammation and metabolism in Perivascular Adipose Tissue could represent novel approaches to restore vascular function during aging. Furthermore, QO58 represents a novel tool for cardiovascular and hypertension research in aging.

  • Perivascular Adipose Tissue: the Sixth Man of the Cardiovascular System.
    Cardiovascular drugs and therapy, 2018
    Co-Authors: Chak Kwong Cheng, Maik Gollasch, Hamidah Abu Bakar, Yu Huang
    Abstract:

    Perivascular Adipose Tissue (PVAT) refers to the local aggregate of Adipose Tissue surrounding the vascular tree, exhibiting phenotypes from white to brown and beige adipocytes. Although PVAT has long been regarded as simply a structural unit providing mechanical support to vasculature, it is now gaining reputation as an integral endocrine/paracrine component, in addition to the well-established modulator endothelium, in regulating vascular tone. Since the discovery of anti-contractile effect of PVAT in 1991, the use of multiple rodent models of reduced amounts of PVAT has revealed its regulatory role in vascular remodeling and cardiovascular implications, including atherosclerosis. PVAT does not only release PVAT-derived relaxing factors (PVRFs) to activate multiple subsets of endothelial and vascular smooth muscle potassium channels and anti-inflammatory signals in the vasculature, but it does also provide an interface for neuron-adipocyte interactions in the vascular wall to regulate arterial vascular tone. In this review, we outline our current understanding towards PVAT and attempt to provide hints about future studies that can sharpen the therapeutic potential of PVAT against cardiovascular diseases and their complications.

  • Perivascular Adipose Tissue (PVAT) in Health and Disease
    Frontiers Research Topics, 2018
    Co-Authors: Maik Gollasch, Stephanie W Watts
    Abstract:

    In 1991, Soltis and Cassis (Clin Exp Hypertens A 1991 13:277-296) published the first paper that the fat Tissue around an artery – Perivascular Adipose Tissue or PVAT – changed how the artery contracted to norepinephrine. Followed later by important work showing that PVAT itself contained vasoactive molecules, the scientific community recognized that PVAT was not simply a store of fat but is a vasoactive Tissue that contributes to the functioning and status of the vessel it surrounds. Our goal for this Frontiers Research Topic is to highlight the significant reach of PVAT in vascular function, from contractility to growth in health and in disease. In doing so, we explicitly place findings that can be taken advantage of in creating new therapies for cardiovascular diseases that continue to challenge our community. These include hypertension, atherosclerosis, and diabetes to name a few

  • A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk
    Current Hypertension Reports, 2016
    Co-Authors: Xiaoming Lian, Maik Gollasch
    Abstract:

    Perivascular Adipose Tissue (PVAT) is now recognized as an important paracrine organ influencing the homeostasis of the vessel wall, regional blood flow and peripheral arterial resistance. There is remarkable phenotypic variability and plasticity of PVAT among various vascular beds, exhibiting phenotypes from white to brown and beige adipocytes. PVAT dysfunction is characterized by disturbed secretion of various adipokines, which, together with endothelial dysfunction, contribute to hypertension and cardiovascular disease (CVD). This brief review describes our current knowledge on PVAT in health and cardiovascular disease, with a special focus on different phenotypes and signaling pathways in adipocytes of PVAT associated with hypertension, obesity and cardiovascular disorders.

  • Regional differences in Perivascular Adipose Tissue impacting vascular homeostasis
    Trends in endocrinology and metabolism: TEM, 2015
    Co-Authors: Maik Gollasch, María S. Fernández-alfonso, Marta Gil-ortega, Beatriz Somoza, Yu Huang
    Abstract:

    Perivascular Adipose Tissue (PVAT) releases several important vasoactive factors with physiological and pathophysiological paracrine effects. A large body of evidence suggests regional phenotypic and functional differences among PVAT depots, depending on the specific vascular bed or different regions in the vascular bed where the PVAT is located. These non-uniform and separate PVATs exert various paracrine effects on vascular structure and function that largely impact disease states, such as endothelial dysfunction, atherosclerosis, or insulin resistance. This emerging view of PVAT function requires considering heterogeneous PVAT as a specialized organ that can differentially regulate vascular function depending on its anatomical location. In this context, the Adipose-vascular axis may represent a novel target for pharmacological intervention in vasculopathy in cardiometabolic disorders.

Johnathan D. Tune - One of the best experts on this subject based on the ideXlab platform.

  • Perivascular Adipose Tissue and Coronary Vascular Disease
    Arteriosclerosis thrombosis and vascular biology, 2014
    Co-Authors: Meredith K. Owen, Jillian N. Noblet, Daniel J. Sassoon, Abass M. Conteh, Adam G. Goodwill, Johnathan D. Tune
    Abstract:

    Coronary Perivascular Adipose Tissue is a naturally occurring Adipose Tissue depot that normally surrounds the major coronary arteries on the surface of the heart. Although originally thought to promote vascular health and integrity, there is a growing body of evidence to support that coronary Perivascular Adipose Tissue displays a distinct phenotype relative to other Adipose depots and is capable of producing local factors with the potential to augment coronary vascular tone, inflammation, and the initiation and progression of coronary artery disease. The purpose of the present review is to outline previous findings about the cardiovascular effects of coronary Perivascular Adipose Tissue and the potential mechanisms by which Adipose-derived factors may influence coronary vascular function and the progression of atherogenesis.

  • Perivascular Adipose Tissue potentiates contraction of coronary vascular smooth muscle influence of obesity
    Circulation, 2013
    Co-Authors: Meredith K. Owen, Frank A Witzmann, Mikaela Mckenney, Xianyin Lai, Zachary C Berwick, Steven P Moberly, Mouhamad Alloosh, Michael Sturek, Johnathan D. Tune
    Abstract:

    Background—This investigation examined the mechanisms by which coronary Perivascular Adipose Tissue (PVAT)–derived factors influence vasomotor tone and the PVAT proteome in lean versus obese swine....

  • epicardial Perivascular Adipose Tissue as a therapeutic target in obesity related coronary artery disease
    British Journal of Pharmacology, 2012
    Co-Authors: Gregory A Payne, Meredith C Kohr, Johnathan D. Tune
    Abstract:

    UNLABELLED Adipose Tissue is an active endocrine and paracrine organ that may influence the development of atherosclerosis and vascular disease. In the setting of obesity, Adipose Tissue produces a variety of inflammatory cytokines (or adipokines) that are known to modulate key mechanisms of atherogenesis. In particular, Adipose Tissue located on the surface of the heart surrounding large coronary arteries (i.e. epicardial Perivascular Adipose Tissue) has been implicated in the pathogenesis of coronary artery disease. The present review outlines our current understanding of the cellular and molecular links between Perivascular Adipose Tissue and atherosclerosis with a focus on potential mechanisms by which epicardial Perivascular Adipose Tissue contributes to obesity-related coronary disease. The pathophysiology of Perivascular Adipose Tissue in obesity and its influence on oxidative stress, inflammation, endothelial dysfunction and vascular reactivity is addressed. In addition, the contribution of specific epicardial Perivascular Adipose-derived adipokines (e.g. leptin, adiponectin) to the initiation and expansion of coronary disease is also highlighted. Finally, future investigative goals are discussed with an emphasis on indentifying novel therapeutic targets and disease markers within Perivascular Adipose Tissue. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.

Anthony M. Heagerty - One of the best experts on this subject based on the ideXlab platform.

  • Modulation of Vascular Reactivity by Perivascular Adipose Tissue (PVAT)
    Current Hypertension Reports, 2018
    Co-Authors: Claudia Agabiti-rosei, Carolina De Ciuceis, Anthony M. Heagerty, Adam Greenstein, Anna Paini, Sarah Withers, Damiano Rizzoni
    Abstract:

    Purpose of Review In this review, we discuss the role of Perivascular Adipose Tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation. Recent Findings PVAT possesses a relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades, it has been shown that PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in Adipose Tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anti-contractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress. Summary Adipose Tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regard.

  • Blockade of the renin-angiotensin system in small arteries and anticontractile function of Perivascular Adipose Tissue.
    Journal of hypertension, 2015
    Co-Authors: Claudia Agabiti Rosei, Sarah B Withers, Laila Belcaid, Carolina De Ciuceis, Damiano Rizzoni, Anthony M. Heagerty
    Abstract:

    BACKGROUND/AIMS In patients with obesity, there is increased inflammation with attendant oxidative stress in Perivascular Adipose Tissue. This has functional consequences with loss of vasodilator adipokine bioavailability. Part of the inflammatory response is mediated by increased activation of the renin-angiotensin-aldosterone axis. Therefore, this study was designed to investigate whether angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can improve the anticontractile function of Perivascular Adipose Tissue. METHODS Segments of rat mesenteric small artery were dissected and mounted in a wire myograph and contracted to incremental doses of norepinephrine in the presence and absence of Perivascular Adipose Tissue and in conditions of normal oxygenation or after hypoxia and incubated with captopril or telmisartan. RESULTS Vessels with Perivascular Adipose Tissue contracted significantly less than arteries with Perivascular Adipose Tissue removed under normal oxygenation conditions, indicating that Perivascular Adipose Tissue exerts an anticontractile effect. Hypoxia induced a loss of this anticontractile effect which could be completely prevented with captopril or telmisartan. CONCLUSION The in-vitro creation of a hypoxic environment can simulate the loss of anticontractile Perivascular Adipose Tissue function seen in vivo in obese patients, and this can be prevented using inhibitors of the renin-angiotensin cascade.

  • Effects of Obesity on Perivascular Adipose Tissue Vasorelaxant Function: Nitric Oxide, Inflammation and Elevated Systemic Blood Pressure
    Journal of vascular research, 2015
    Co-Authors: Reza Aghamohammadzadeh, Adam Greenstein, Richard D. Unwin, Anthony M. Heagerty
    Abstract:

    Introduction: Perivascular Adipose Tissue (PVAT) surrounds most vessels in the human body. Healthy PVAT has a vasorelaxant effect which is not observed in obesity

  • Perivascular Adipose Tissue-derived adiponectin activates BKCa channels to induce anticontractile responses
    American journal of physiology. Heart and circulatory physiology, 2013
    Co-Authors: Fiona M Lynch, Sarah B Withers, Zhihong Yao, Matthias Werner, Gillian Edwards, Arthur H. Weston, Anthony M. Heagerty
    Abstract:

    This study aims to identify the potential mechanisms by which Perivascular Adipose Tissue (PVAT) reduces tone in small arteries. Small mesenteric arteries from wild-type and large-conductance Ca2+-...

  • Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of Perivascular Adipose Tissue.
    Annals of Medicine, 2012
    Co-Authors: Reza Aghamohammadzadeh, Anthony M. Heagerty
    Abstract:

    The advent of the obesity epidemic has highlighted the need to re-assess more closely the pathophysiology of obesity-related hypertension with the aim of identifying new therapies. In this article, we review the role of the renin-angiotensin-aldosterone system, sympathetic nervous system, and inflammation in relation to the pathophysiology of this condition. We also discuss the potential role of the Perivascular Adipose Tissue in the context of obesity-related hypertension.

Claudia Agabitirosei - One of the best experts on this subject based on the ideXlab platform.

  • modulation of vascular reactivity by Perivascular Adipose Tissue pvat
    Current Hypertension Reports, 2018
    Co-Authors: Am Heagerty, Sarah B Withers, Carolina De Ciuceis, Adam Greenstein, Claudia Agabitirosei, Anna Paini, Damiano Rizzoni
    Abstract:

    In this review, we discuss the role of Perivascular Adipose Tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation. PVAT possesses a relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades, it has been shown that PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in Adipose Tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anti-contractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress. Adipose Tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regard.

Shuntaro Ikeda - One of the best experts on this subject based on the ideXlab platform.