Adipose Specific Loss of PCPE2 Promotes Microvascular Endothelial Dysfunction and Decreased Angiogenic Potential

Procollagen C‐endopeptidase enhancer 2 (PCPE2) is an extracellular matrix protein which regulates the oligomerization of the high and low‐density lipoprotein (HDL/LDL) receptors that enable cellular uptake of HDL/LDL from the extracellular matrix under healthy conditions. To evaluate Effect of adipose PCPE2 floxed mice were crossed with mice expressing adipose specific cre recombinase. We hypothesized elevated lipid levels induced by PCPE2 KO mice vascular function and angiogenic potential. In Adipose specific PCPE2 KO we found that due to the inability of lipoprotein lipids in HDL to be taken up by the adipocytes, the concentration of HDL in the plasma compartment significantly increased. Using this model vascular function was evaluated using pressure mayo graph setup. Endothelial function was determined by dose response curves to ACH or increasing levels of shear stress. Smooth muscle function was tested by response to Papaverine. Angiogenic potential was evaluated by embedding sections of brown adipose tissue in Matrigel and vascular growth measured by sprout formation. Statistical significance was established using a student t‐test P<0.05 vs. CTRL. Adipose specific PCPE2 KO resulted in elevated plasma lipid levels as elevated by insert numbers. Homozygous loss of Ad‐PCPE2 resulted in decreased endothelial function compared to control mice. Interestingly heterozygote deletion of Ad‐PCPE2 deletion trended toward increase in endothelial mediated dilation (Fig. 1A and B). Smooth muscle function was not affected by either genotype (Fig. 1C). Angiogenic Potential was significantly decreased in both heterozygote Ad‐PCPE2 KO mice compared to CTRLs (% growth Mean, SEM, N: CTRL 3.05±1.31, 6; Het 1.07±0.59*, 4) In conclusion, our data suggest that ad‐PCPE2 loss of function elevated plasma lipid levels that promote endothelial dysfunction as assessed by decreased vasodilator capacity and angiogenic potential. Support or Funding Information Funded by MST HL127649 and HL138907; AMB R01‐HL133029‐02 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .