TY - JOUR

T1 - Disruption of GPR35 Signaling in Bone Marrow-Derived Cells Does Not Influence Vascular Inflammation and Atherosclerosis in Hyperlipidemic Mice

AU - Baumgartner, Roland

AU - Casagrande, Felipe B.

AU - Mikkelsen, Randi B.

AU - Berg, Martin

AU - Polyzos, Konstantinos A.

AU - Forteza, Maria J.

AU - Arora, Aastha

AU - Schwartz, Thue W.

AU - Hjorth, Siv A.

AU - Ketelhuth, Daniel F. J.

PY - 2021

Y1 - 2021

N2 - G-protein-coupled receptor-35 (GPR35) has been identified as a receptor for the tryptophan metabolite kynurenic acid (KynA) and suggested to modulate macrophage polarization in metabolic tissues. Whether GPR35 can influence vascular inflammation and atherosclerosis has however never been tested. Lethally irradiated LdlrKO mice were randomized to receive GPR35KO or wild type (WT) bone marrow transplants and fed a high cholesterol diet for eight weeks to develop atherosclerosis. GPR35KO and WT chimeric mice presented no difference in the size of atherosclerotic lesions in the aortic arch (2.37 +/- 0.58% vs. 1.95 +/- 0.46%, respectively) or in the aortic roots (14.77 +/- 3.33% vs. 11.57 +/- 2.49%, respectively). In line with these data, no changes in the percentage of VCAM-1+, IA(b) + cells, and CD3+ T cells, as well as alpha smooth muscle cell actin expression, was observed between groups. Interestingly, the GPR35KO group presented a small but significant increase in CD68+ macrophage infiltration in the plaque. However, in vitro culture experiments using bone marrow-derived macrophages from both groups indicated that GPR35 plays no role in modulating the secretion of major inflammatory cytokines. Our study indicates that GPR35 expression does not play a direct role in macrophage activation, vascular inflammation, and the development of atherosclerosis.

AB - G-protein-coupled receptor-35 (GPR35) has been identified as a receptor for the tryptophan metabolite kynurenic acid (KynA) and suggested to modulate macrophage polarization in metabolic tissues. Whether GPR35 can influence vascular inflammation and atherosclerosis has however never been tested. Lethally irradiated LdlrKO mice were randomized to receive GPR35KO or wild type (WT) bone marrow transplants and fed a high cholesterol diet for eight weeks to develop atherosclerosis. GPR35KO and WT chimeric mice presented no difference in the size of atherosclerotic lesions in the aortic arch (2.37 +/- 0.58% vs. 1.95 +/- 0.46%, respectively) or in the aortic roots (14.77 +/- 3.33% vs. 11.57 +/- 2.49%, respectively). In line with these data, no changes in the percentage of VCAM-1+, IA(b) + cells, and CD3+ T cells, as well as alpha smooth muscle cell actin expression, was observed between groups. Interestingly, the GPR35KO group presented a small but significant increase in CD68+ macrophage infiltration in the plaque. However, in vitro culture experiments using bone marrow-derived macrophages from both groups indicated that GPR35 plays no role in modulating the secretion of major inflammatory cytokines. Our study indicates that GPR35 expression does not play a direct role in macrophage activation, vascular inflammation, and the development of atherosclerosis.

KW - atherosclerosis

KW - GPR35

KW - inflammation

KW - immunometabolism

KW - kynurenine

KW - tryptophan

KW - macrophages

KW - KYNURENIC ACID

U2 - 10.3390/metabo11070411

DO - 10.3390/metabo11070411

M3 - Journal article

C2 - 34201526

VL - 11

JO - Metabolites

JF - Metabolites

SN - 2218-1989

IS - 7

M1 - 411

ER -