Perivascular adipose tissue in vascular function: does locally synthesized angiotensinogen play a role?

ABSTRACT In recent years, perivascular adipose tissue (PVAT) research has gained special attention in an effort to understand its involvement in vascular function. PVAT is recognized as an important endocrine organ that secretes pro- and anti-contractile factors, including components of the renin-angiotensin-aldosterone system, in particular angiotensinogen. This review critically addresses the occurrence of angiotensinogen in PVAT, its release into the blood stream, and its contribution to the generation and effects of angiotensins (notably angiotensin-(1-7) and angiotensin II) in the vascular wall. It describes that the introduction of transgenic animals, expressing angiotensinogen at 0, 1 or more specific location(s), combined with the careful measurement of angiotensins, have revealed that the assumption that PVAT independently generates angiotensins from locally synthesized angiotensinogen is incorrect. Indeed, selective deletion of angiotensinogen from adipocytes did not lower circulating angiotensinogen, neither under a control diet nor under a high-fat diet, and only liver-specific angiotensinogen deletion resulted in the disappearance of angiotensinogen from blood plasma and adipose tissue. An entirely novel scenario therefore develops, supporting local angiotensin generation in PVAT that depends on the uptake of both angiotensinogen and renin from blood, in addition to the possibility that circulating angiotensins exert vascular effects. The review ends with a summary of where we stand now, and recommendations for future research.