PVAT
Years ago: An adrenergic system in PVAT…The study depicted above was our first deep foray into perivascular adipose tissue (PVAT). Using HPLC, we have discovered time and again that the PVATs around rodent and human blood vessels contains significant amounts of amines, especially norepinephrine (NE), the neurotransmitter of the sympathetic nervous system. Importantly, these catecholamines are vasoactive, meaning that if we stimulate their release, they cause vascular contraction! As such, the fat living right outside the vessel is poised to change how the vessel functions, and this is relevant to CV disease. Our goal is to determine whether a true adrenergic system (synthesis, storage, release and uptake) of NE exists in PVAT, and how this changes in obesity associated hypertension. The references in (A) supports the existence and release of functional catecholamines as facilitated by organic cation transporter 3 (B). The predominant release of NE over 5-HT was validated with use of fenfluramine (C), and Maleeha Ahmad, Nadia Sayal-Lopez, Emma Darios, Alex Ismail, Robert Burnett and Arun Anantharam were the first to demonstrate functional VMAT vesicles in the adipocytes of PVAT (D). The importance of OCT3 has been reproduced by other investigators. In 2024, this is STILL a goal. We don’t know what endogenous substance causes the adipocyte stored amines to be released.
2020: We’ve since expanded this area of research significantly with a submission of a Program Project Grant (PPG) to NIH. This involves MANY investigators throughout MSU, and in departments outside of PHM/TOX. Our goal of this project is to test that PVAT is a key Integrator of vascular health…and it is (so data say!).
2022: The work above led to a Program Project Grant funded by NHLBI that investigates PVAT as a Central Integrator in vascular health. The adrenergic project above was adopted in part within this PPG, but the PPG encompasses far more science.
2024: Here is the separate website for the PPG: http://www.pvatppgmsu.com