Perivascular fat, AMP-activated protein kinase and vascular diseases.
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.
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
T A M
TA
Almabrouk
M A
MA
Ewart
I P
IP
Salt
S
S
Kennedy
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050154:Adiposity; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014652:Vascular Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D002317:Cardiovascular Agents; D020536:Enzyme Activators; D055372:AMP-Activated Protein Kinases
AMP-activated protein kinase; adipocytes; adiponectin; atherosclerosis; diabetes; hypertension; leptin; metformin; perivascular fat; vascular reactivity