Chemerin is resident to vascular tunicas and contributes to vascular tone

Abstract

The adipokine chemerin may support blood pressure, evidenced by a fall in mean arterial pressure after whole body antisense oligonucleotide (ASO)-mediated knockdown of chemerin protein in rat models of normal and elevated blood pressure. While the liver is the greatest contributor of circulating chemerin, liver-specific ASOs that abolished hepatic-derived chemerin did not change blood pressure. Thus, other sites must produce the chemerin that supports blood pressure. We hypothesize the vasculature as a source of chemerin independent of the liver that supports arterial tone. RNAScope®, PCR, Western analyses, ASOs, isometric contractility, and radiotelemetry were used in the Dahl salt sensitive (SS) rat (male and female) on a normal diet. Rarres2 mRNA was detected in the smooth muscle, adventitia, and perivascular adipose tissue of the thoracic aorta. Chemerin protein was detected immunohistochemically in the endothelium, smooth muscle cells, adventitia, and perivascular adipose tissue. Chemerin colocalized with the vascular smooth muscle marker a-actin and the adipocyte marker perilipin. Importantly, chemerin protein in the thoracic aorta was not reduced when liver-derived chemerin was abolished by a liver-specific ASO against chemerin. Chemerin protein was similarly absent in arteries from a newly created global chemerin knockout in Dahl SS rats. Inhibition of the receptor Chemerin1 by the receptor antagonist CCX832 resulted in loss of vascular tone that supports potential contributions of chemerin by both PVAT and the media. These data suggest that vessel-derived chemerin may support vascular tone locally through constitutive activation of Chemerin1. This posits chemerin as a potential therapeutic target in blood pressure regulation.

Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia

“…Given the existence of multiple isoforms in the case of both chemerin and PlGF, 8,10,[32][33][34][35][36] we used human retinoic acid receptor responder 2 small interfering RNA (small interfering-Chemerin, 10 nmol/L; Thermo Fisher Scientific, 12179), and human PlGF siRNA (small interfering-PlGF, 50 nmol/L; Thermo Fisher Scientific, 143789) to knockdown chemerin and PlGF in HepG2 cells (ATCC, Manassas, VA) and placenta villous explants. 37,38 A nontargeting siRNA (small interfering control) was used as a negative control (Thermo Fisher Scientific, AM4611).…”