knockout in Dahl SS rats. We administered the ASO to the KO rat to test that the ASO against chemerin reduced blood pressure by preventing chemerin production only. However, the ASO against chemerin lowered blood pressure both in WT and KO rats, indicating the ASO has off-target effects. This finding necessitated use of CCX832 and the chemerin KO rat to understand chemerin's role in cardiovascular health and disease. Here we test the hypothesis that CCX832 administration or genetic chemerin loss will reveal chemerin's role in driving adiposity-associated hypertension and vascular stiffness. CCX832 reduced blood pressure in high fat diet (HFD)-induced, but not high salt diet (HSD)-induced hypertensive males, supporting that chemerin's effects on blood pressure are obesity-related and at least in part Chemerin1-mediated. In addition, genetic chemerin loss blunted development of HFD-induced hypertension in males but, interestingly, exacerbated it in females. Aortic arch stiffening was prevented in the KO male rat on HFD, but no differences were observed in females. KO males on HFD had significantly lower collagen deposition in thoracic aorta than control diet (CD) or HFD-fed male WTs, while there were no significant differences among females. Our findings support chemerin as a sex-dependent driver of adiposity-associated hypertension and vascular stiffness and prompt broader investigation into chemerin's role in other vascular or sex-specific diseases.
Wabel et al. (Mon,) studied this question.