Perivascular fat, AMP-activated protein kinase and vascular diseases

Almabrouk, T.A.M. , Ewart, M.-A., Salt, I.P. and Kennedy, S. (2014) Perivascular fat, AMP-activated protein kinase and vascular diseases. British Journal of Pharmacology, 171(3), pp. 595-617. (doi: 10.1111/bph.12479) (PMID:24490856) (PMCID:PMC3969075)

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Abstract

Perivascular adipose tissue (PVAT) is an active endocrine and paracrine organ that modulates vascular function, with implications for the pathophysiology of cardiovascular disease (CVD). Adipocytes and stromal cells contained within PVAT produce mediators (adipokines, cytokines, reactive oxygen species and gaseous compounds) with a range of paracrine effects modulating vascular smooth muscle cell contraction, proliferation and migration. However, the modulatory effect of PVAT on the vascular system in diseases, such as obesity, hypertension and atherosclerosis, remains poorly characterized. AMP-activated protein kinase (AMPK) regulates adipocyte metabolism, adipose biology and vascular function, and hence may be a potential therapeutic target for metabolic disorders such as type 2 diabetes mellitus (T2DM) and the vascular complications associated with obesity and T2DM. The role of AMPK in PVAT or the actions of PVAT have yet to be established, however. Activation of AMPK by pharmacological agents, such as metformin and thiazolidinediones, may modulate the activity of PVAT surrounding blood vessels and thereby contribute to their beneficial effect in cardiometabolic diseases. This review will provide a current perspective on how PVAT may influence vascular function via AMPK. We will also attempt to demonstrate how modulating AMPK activity using pharmacological agents could be exploited therapeutically to treat cardiometabolic diseases.

Item Type:Articles (Other)
Keywords:adipocytes, adiponectin, AMP-activated protein kinase, atherosclerosis, diabetes, leptin, perivascular fat, hypertension, vascular reactivity, metformin
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Simon and ALMABROUK, Tarek Ali Mohamed and Ewart, Dr Marie-Ann and Salt, Dr Ian
Authors: Almabrouk, T.A.M., Ewart, M.-A., Salt, I.P., and Kennedy, S.
Subjects:R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:British Journal of Pharmacology
Journal Abbr.:BJP
Publisher:Wiley
ISSN:0007-1188
ISSN (Online):1476-5381

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
547511Involvement of AMPK in calcium regulation in atherosclerotic blood vessels.Marie-Ann EwartBritish Heart Foundation (BHF)PG/10/70/28384RI CARDIOVASCULAR & MEDICAL SCIENCES