Abstract 13: Vascular Chemerin, Particularly from PVAT, contributes to Norepinephrine and Serotonin-Induced Vasoconstriction and Vascular Stiffness in a Sex-Dependent Manner

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 81; no. Suppl_1
• Main Authors: Wabel, Emma, Krieger-Burke, Teresa, Watts, Stephanie
• Format: Journal Article
• Language: English
• Published: 01.09.2024
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.81.suppl_1.13

Abstract only The adipokine chemerin has been implicated in healthy blood pressure maintenance and adiposity-associated hypertension, evidenced by falls in mean arterial pressure after administration of an antisense oligonucleotide against chemerin in Dahl SS rats. Circulating levels of chemerin are positively associated, in humans, with hypertension and aortic stiffening—a blood pressure-independent risk factor of cardiovascular disease. While chemerin’s role in blood pressure is observed in whole animals, mechanisms of chemerin’s influence on vascular health and disease remain unknown. Chemerin causes direct vasoconstriction through its main receptor Chemerin1 and indirect vasoconstriction by amplifying electrical field stimulation-induced contraction. We identified chemerin production at the vasculature—the blood vessel and its perivascular adipose tissue (PVAT)—and are working to discover the mechanistic role of vascular chemerin in blood vessel function and disease. Using RNAScope®, QPCR, isometric contractility, western blot, and in vivo imaging, we test the hypothesis that vascular chemerin increases arterial contractility through Chemerin1 and plays a role in aortic stiffening. RNAScope® probes detected CMKLR1 expression in the tunica media and PVAT of the thoracic aorta. QPCR revealed Rarres2 expression was higher in the PVAT, and CMKLR1 expression was higher in the media. Chemerin1 antagonism via the selective inhibitor CCX832 (1μM) significantly reduced maximal contraction to both norepinephrine (NE) and serotonin (5-HT) (see figure), but not angiotensin II, in the male rat +PVAT groups. This supports that PVAT-derived chemerin plays a role in sympathetic stimulation of the vasculature. Interestingly, in females, this change in contractile response to NE and 5-HT was not observed. Western blot showed that females express significantly lower levels of chemerin protein in PVAT, suggesting PVAT as the primary source of active chemerin. Finally, male, but not female, genetic chemerin knockout Dahl SS rats have lower aortic arch pulse wave velocity than wild types (M WT: 3.7 ± .7 M KO: 1.4 ± .3 F WT: 2.6 ± .5, F KO: 1.5 ± .3 m/s, N=4-6/group), highlighting a role of chemerin in aortic stiffening. Thus, chemerin, sourced by the PVAT, plays a significant role in vascular contractility and aortic stiffening in males. Future work will determine if chemerin’s influence is amplified in adiposity-associated hypertension, where chemerin levels are elevated in both sexes.