Lipoprotein lipase underlies the vascular anti- contractile effect of perivascular adipose tissue (PVAT)

Physiologically, perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature. This effect is mediated by the biosynthesis and liberation of a myriad of anti-contractile molecules (e.g., adipokines). However, this anti-contractile function generally is lost with aging and cardiovascular diseases such as hypertension and diabetes. Lipoprotein lipase (LPL) is an enzyme classically known for hydrolyzing triglycerides into free fatty acids and glycerol. However, it is unknown whether LPL underlies the anti-contractile effect of PVAT. Specifically, we hypothesized that by inhibiting lipoprotein lipase (LPL) activity with Atglistatin, we would abolish the anti-contractile effect of PVAT. To test this hypothesis, mesenteric resistance arteries (MRA), with and without PVAT, were isolated from 3-month-old male Wistar rats and mounted on a wire myograph. Phenylephrine concentration-response curves were performed with and without Atglistatin (10 -5 M). As expected, PVAT exerted a significant anti-contractile effect on phenylephrine-induced contraction [Emax (mN), -PVAT-vehicle: 18.1±3.0 vs. +PVAT-vehicle: 7.1±1.1, p<0.05]. Incubation of MRA with intact PVAT with Atglistatin significantly increased contraction [Emax (mN), +PVAT-vehicle: 7.1±1.1vs. +PVAT-Atglistatin: 22.6±4.2, p<0.05], suggesting that LPL is indeed important for the anti-contractile effect of PVAT. Crucially, no difference was observed with Atglistatin in MRA lacking PVAT [Emax (mN), -PVAT-vehicle: 18.1±3.0 vs. -PVAT-Atglistatin: 18.5±2.9, p>0.05], indicating that Atglistatin was not increasing contraction via non-PVAT-dependent mechanisms. Overall, these data suggest that LPL is an important mechanism mediating the anti-contractile effect of PVAT and that reduced LPL activity could be contributing to pro-contractile PVAT in aging and cardiovascular diseases. NHLBI (R00HL151889), NIGMS (1P20GM103641 - Pilot Project), UofSC SOM (Startup funds) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.