Postprandial lipoproteins and the molecular regulation of vascular homeostasis

Abstract

Blood levels of triglyceride-rich lipoproteins (TRL) increase postprandially, and a delay in their clearance results in postprandial hyperlipidemia, an important risk factor in atherosclerosis development. Atherosclerosis is a multifactorial inflammatory disease, and its initiation involves endothelial dysfunction, invasion of the artery wall by leukocytes and subsequent formation of foam cells. TRL are implicated in several of these inflammatory processes, including the formation of damaging free radicals, leukocyte activation, endothelial dysfunction and foam cell formation. Recent studies have provided insights into the mechanisms of uptake and the signal transduction pathways mediating the interactions of TRL with leukocytes and vascular cells, and how they are modified by dietary lipids. Multiple receptor and non-receptor mediated pathways function in macrophage uptake of TRL. TRL also induce expression of adhesion molecules, cyclooxygenase-2 and heme-oxygenase-1 in endothelial cells, and activate intracellular signaling pathways involving mitogen-activated protein kinases, NF-κB and Nrf2. Many of these effects are strongly influenced by dietary components carried in TRL. There is extensive evidence indicating that raised postprandial TRL levels are a risk factor for atherosclerosis, but the molecular mechanisms involved are only now becoming appreciated. Here, we review current understanding of the mechanisms by which TRL influence vascular cell function.

Keywords: 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine; ABC; AMP kinase; AMPK; AP; ATP binding cassette transporter; Akt; Apo; C reactive protein; CD; CM; CMR; COX; CREB; CRP; DHA; EC; EGF; EPA; EPC; ERK; Egr; Endothelial cells; FAK; FFA; GPIHBP1; HAEC; HDL; HMDM; HO; HSPG; HUVEC; ICAM; IFN; IL; Inflammation; IκB; JNK; LDL; LDLR; LOX; LPL; LPS; LR11; LRP; M1; M2; MAPK; MCP; MEK; MIP; MMP; MUFA; Macrophages; Monocytes; Mox; NAD(P)H oxidase; NF-κB; NO; Nox; Nrf; P; PAI-1; PAPC; PGE(2); PKC; PL; POA; PPAR; PUFA; Postprandial lipemia; RAP; RLP; ROS; RXR; SFA; SR; TG; TGF; TLR; TNF; TRL; Triglyceride-rich lipoproteins; V; VCAM; VE cadherin; VEGF; VLDL; VLDLR; VSMC; activator protein; alternatively activated macrophages; apoB48R; apolipoprotein; apolipoprotein B48 receptor; c-Jun N-terminal kinase; cAMP response element binding; chylomicron remnants; chylomicrons; classically activated macrophages; cluster of differentiation; cyclooxygenase; docosahexaenoic acid; eNOS; early growth response protein; eicosapentaenoic acid; endothelial cell; endothelial nitric oxide synthase; endothelial progenitor cell; epidermal growth factor; extracellular-signal-regulated kinase; focal adhesion kinase; free fatty acid; glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1; hemeoxygenase; heparan sulfate proteoglycans; high density lipoprotein; human aortic endothelial cell; human monocyte-derived macrophages; human umbilical vein endothelial cells; inhibitor of κB; intercellular adhesion molecule; interferon; interleukin; lectin-like oxidized low density lipoprotein receptor; lipopolysaccharide; lipoprotein lipase; low density lipoprotein; low density lipoprotein receptor; low density lipoprotein receptor-related protein; macrophage inflammatory protein; macrophage phenotype induced by oxidised phospholipids; matrix-metalloproteinase; mitogen activated protein kinase kinase; mitogen-activated kinase; monocyte chemoattractant protein; monousaturated fatty acids; nitric oxide; nuclear factor (erythroid-derived 2)-like 2; nuclear factor-κB; ox; oxidized; peroxisome proliferator-activated receptor; phospholipid; plasminogen activator inhibitor type 1; polyunsaturated fatty acids; pomace oil supplemented with oleanolic acid test meal; pomace olive oil test meal; prostglandin E2; protein kinase B; protein kinase C; reactive oxygen species; receptor associated protein; remnant-like particles; retinoid X receptor; saturated fatty acids; scavenger receptor; sortilin-related receptor; toll-like receptor; transforming growth factor; triacylglycerol; triglyceride-rich lipoproteins; tumor necrosis factor; vascular cell adhesion molecule; vascular endothelial cadherin; vascular endothelial growth factor; vascular smooth muscle cells; very low density lipoprotein; very low density lipoprotein receptor; virgin olive oil test meal.