PVAT as a vasoactive adipose depot: chemerin as a vasocontrictor

This is one of our discoveries that changes how we think about the function of perivascular adipose tissue (PVAT, adipose tissue surrounding blood vessels).  First, we discovered the expression of the adipokine chemerin in PVAT (a), and were the first to show this substance which is elevated in obesity causes vasoconstriction.  We have recently made a chemerin KO rat using Crispr Cas technology that allowed us to knockdown this adipokine (d).  Important findings include the ability of chemerin to ‘tweak’ the sympathetic nervous system that innervates blood vessels (c), and the signaling of the chemerin receptor in the vasculature (b).

In 2019, we received a Transformational Project Award from the American Heart Association to develop and test the idea that selective delivery of a tool we use (antisense oligonucleotide) to the adipocyte would reduce blood pressure in an adiposity based model. The amazing things about ASO is their half-life - 2 to 4 weeks! The potential of treating obesity association hypertension, a significant health problem right now, is very real.

a. Watts, S.W., Dorrance, A.M., Penfold, M.E., Rourke, J.L., Sinal, C.J., Seitz, B., Sullivan, T.J., Charvat, T.T., Thompson, J.M., Burnett, R. and Fink, G.D.: Chemerin connects fat to arterial contraction.  Art. Thromb. Vasc. Biol, 33:1320-1328, 2013.  PMCID:PMC3752465.

b. Ferland D, Darios, E. S., Neubig, R. R., Sjogren, B., Truong, N., Torres, R., Dexheimer, T. S., Thompson J. M. and Watts, S. W.: Chemerin-induced arterial contraction is Gi and calcium-dependent, Vasc Pharmacology, 88:30-41, 2017.

c. Darios, E. S., Winner, B. M., Charvat, T., Karsinksi, A., Punna, S. and Watts, S.W.: The adipokine chemerin amplifies electrical field stimulated contraction in the isolated superior mesenteric artery,  Am J Physiol Heart Circ Physiol, 311:H498-H507, 2016.

D. Watts, S. W., Darios, E. M., Mullick, A. E., Garver, H., Saunders T. L., Hughes, E. D., Filipiak, W. E., Zeidler, M. G., McMullen, N., Sinal, C. J., Kumar, R. K., Ferland, D. J. and Fink, G. D.: The chemerin knockout rat reveals chemerin dependence in female but not male experimental hypertension, FASEB J, doi:10/1096/fj.201800479,  2018.