The role of the scavenger receptor CD36 in regulating mononuclear phagocyte trafficking to atherosclerotic lesions and vascular inflammation

Abstract

Our results support a role for CD36 signalling in the regulation of mononuclear phagocyte trafficking to atherosclerotic-prone sites and in the associated vascular wall inflammation.

Molecular Biology of Atherosclerosis

“…As for MSR above, results for KO with this receptor have been somewhat variable (654) but generally confirmatory (716). Confirmed also in LDLR KO BMT (1121).…”

“…JAK2 activation was dependent on Src but likely also on PYK2 with signaling through CD36 (716). In another study, increased expression of STAT3 by adenoassociated virus delivery of human STAT3 appeared protective with a 15% reduction in atherosclerosis.…”

“…Endothelial PYK2 also mediates Ras and ERK1/2 activation mediated by LPC (1488), and LPA (lysophosphatidic acid), as well as the bradykinin receptor (426). PYK2 supports leukocyte adhesion to fibronectin (through integrin ␤3) (586), macrophage migration (1341), IL-10 production in macrophages in response to zymosan (which signals through the ITAM-containing Dectin receptor with Syk activation) (894), macrophage activation through CD36 binding of oxidized phospholipids (716), and neutrophil degranulation (877). VSMC proliferation induced by PDGF is dependent on PYK2 (1404).…”

“…Active PKC and Rac1 promote assembly and activation of NOX2 to enhance ROS production (1210). These pathways provide greater understanding of the marked reduction in atherosclerosis after CD36 KO or pharmacological CD36 inhibition in mice (716).…”

Vav Family Rho Guanine Nucleotide Exchange Factors Regulate CD36-mediated Macrophage Foam Cell Formation

“…In this setting CD36-mediated lipid uptake cannot be mitigated by efflux mechanisms, thereby contributing to foam cell formation. Furthermore, activation of CD36-mediated intracellular signaling cascades promotes vascular inflammation and interferes with macrophage migration, leading to their accumulation in the vessel wall (27,28). Although there has been some controversy about the contribution of CD36 to atherogenesis (29), studies of several murine in vivo model systems, including high fat diet-stressed apoE Ϫ/Ϫ and LDLR Ϫ/Ϫ strains crossed into at least two CD36 Ϫ/Ϫ strains, as well as studies of CD36 Ϫ/Ϫ bone marrow chimeras and CD36 inhibitor-treated mice have shown dramatically smaller plaque lesions and/or less complex lesions with less aortic cholesterol in the absence of functional CD36 (5-8, 30, 31).…”