Entry Name Lipid and atherosclerosis
Description Atherosclerosis is a chronic inflammatory disease marked by a narrowing of the arteries from lipid-rich plaques present within the walls of arterial blood vessels. It represents the root cause of the majority of cardiovascular diseases (CVDs) and their complications, including conditions such as coronary artery disease, myocardial infarction and stroke. An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for genesis of atherosclerosis. LDL can accumulate within the blood vessel wall and undergo modification by oxidation. Oxidized LDL (oxLDL) leads to endothelial dysfunction leading to expression of adhesion molecules and recruitment of monocyte in subendothelial space. The monocytes proliferate, differentiate into macrophages, and take up the lipoproteins, forming cholesterol-engorged "foam cells." With the time, the foam cells die, leaving a 'necrotic core' of crystalline cholesterol and cell debris. Smooth muscle cells proliferate and migrate into the region, laying down a protective cap over the lesion. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which mediates the recognition and internalization of oxLDL, is involved in all of these events critical in the pathogenesis of atherosclerosis.
Class Human Diseases; Cardiovascular diseaseBRITE hierarchy
Pathway map Disease Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K01388 MMP1; matrix metalloproteinase-1 (interstitial collagenase) [EC:3.4.24.7 ]
K01394 MMP3; matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17 ]
K02084 APAF1; apoptotic protease-activating factor
K02158 BAD; Bcl-2-antagonist of cell death
K02159 BAX; apoptosis regulator BAX
K02161 BCL2; apoptosis regulator Bcl-2
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03160 TNFRSF5, CD40; tumor necrosis factor receptor superfamily member 5
K03161 TNFSF5, CD40L, CD154; tumor necrosis factor ligand superfamily member 5
K03174 TRAF3; TNF receptor-associated factor 3
K03237 EIF2S1; translation initiation factor 2 subunit 1
K03283 HSPA1_6_8; heat shock 70kDa protein 1/6/8
K04079 HSP90A, htpG; molecular chaperone HtpG
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04353 RAP1A; Ras-related protein Rap-1A
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04379 FOS; proto-oncogene protein c-fos
K04389 TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390 TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04391 CD14; monocyte differentiation antigen CD14
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04393 CDC42; cell division control protein 42
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04426 MAP3K5, ASK1; mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04430 MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04451 TP53, P53; tumor protein p53
K04452 DDIT3, GADD153; DNA damage-inducible transcript 3
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04513 RHOA; Ras homolog gene family, member A
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04519 IL1B; interleukin 1 beta
K04570 BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04692 STAT3; signal transducer and activator of transcription 3
K04721 TNFSF10, TRAIL, CD253; tumor necrosis factor ligand superfamily member 10
K04722 TNFRSF10A_B, TRAILR1_2, DR4_5, CD261_2; tumor necrosis factor receptor superfamily member 10A/B
K04726 BID; BH3 interacting domain death agonist
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K05399 LBP; lipopolysaccharide-binding protein
K05400 LY96, MD-2; lymphocyte antigen 96
K05403 TIRAP; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K05408 CCL3; C-C motif chemokine 3
K05409 TIRP, TRAM; TRIF-related adaptor molecule
K05411 IRF3; interferon regulatory factor 3
K05482 IL18, IL1F4; interleukin 18
K05505 CXCL1_2_3, GRO; C-X-C motif chemokine 1/2/3
K05638 NFE2L2, NRF2; nuclear factor erythroid 2-related factor 2
K05641 ABCA1; ATP-binding cassette, subfamily A (ABC1), member 1
K05679 ABCG1; ATP-binding cassette, subfamily G (WHITE), member 1
K05730 VAV; guanine nucleotide exchange factor VAV
K05842 TRIF; toll-like receptor adapter molecule 1
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06276 PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1 ]
K06490 ICAM1, CD54; intercellular adhesion molecule 1
K06494 SELE, CD62E; selectin, endothelial cell
K06496 SELP, CD62P; selectin, platelet
K06527 VCAM1, CD106; vascular cell adhesion molecule 1
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07211 IKBKE, IKKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K07827 KRAS, KRAS2; GTPase KRas
K07836 RAP1B; Ras-related protein Rap-1B
K08008 NOX1, MOX1; NADPH oxidase 1
K08009 CYBA, P22PHOX; cytochrome b-245, alpha polypeptide
K08010 NCF2, P67PHOX; neutrophil cytosolic factor 2
K08011 NCF1, P47PHOX; neutrophil cytosolic factor 1
K08012 NCF4, P40PHOX; neutrophil cytosolic factor 4
K08524 RXRA, NR2B1; retinoid X receptor alpha
K08525 RXRB, NR2B2; retinoid X receptor beta
K08526 RXRG, NR2B3; retinoid X receptor gamma
K08530 NR1C3, PPARG; peroxisome proliferator-activated receptor gamma
K08757 APOA1; apolipoprotein A-I
K08760 APOA4; apolipoprotein A-IV
K08763 OLR1; oxidised low-density lipoprotein receptor 1
K08852 ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [EC:2.7.11.1 3.1.26.-]
K08860 EIF2AK3, PERK; eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1 ]
K09027 XBP1; X box-binding protein 1
K09054 ATF6A; cyclic AMP-dependent transcription factor ATF-6 alpha
K09364 POU2F, OTF; POU domain transcription factor, class 2
K09447 IRF7; interferon regulatory factor 7
K09487 HSP90B, TRA1; heat shock protein 90kDa beta
K09489 HSPA4; heat shock 70kDa protein 4
K10030 IL8, CXCL8; interleukin 8
K10159 TLR2, CD282; toll-like receptor 2
K10160 TLR4, CD284; toll-like receptor 4
K10169 TLR6, CD286; toll-like receptor 6
K10950 ERO1L; ERO1-like protein alpha [EC:1.8.4.-]
K12330 ARHGEF1; Rho guanine nucleotide exchange factor 1
K12473 LDLR; low-density lipoprotein receptor
K12499 CCL5; C-C motif chemokine 5
K12650 TANK; TRAF family member-associated NF-kappa-B activator
K12799 PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD
K12800 NLRP3, PYPAF1; NACHT, LRR and PYD domains-containing protein 3
K14624 CCL2, MCP1; C-C motif chemokine 2
K17332 NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333 NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17683 CYP2A6; cytochrome P450 family 2 subfamily A6 [EC:1.14.14.-]
K17709 CYP2B6; cytochrome P450 family 2 subfamily B6 [EC:1.14.14.-]
K19722 AGER, RAGE; receptor for advanced glycosylation end products
K20053 VLDLR; very low-density lipoprotein receptor
K21421 NOX2, GP91, CYBB; NADPH oxidase 2 [EC:1.-.-.-]
K26598 HSPA2; heat shock 70kDa protein 2
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C21011 [Protein]-N(epsilon)-(carboxymethyl)lysine
C21012 [Protein]-N(epsilon)-(carboxyethyl)lysine
Reference Authors Hopkins PN
Title Molecular biology of atherosclerosis.
Journal Reference Authors Weber C, Noels H
Title Atherosclerosis: current pathogenesis and therapeutic options.
Journal Reference Authors Tabas I, Garcia-Cardena G, Owens GK
Title Recent insights into the cellular biology of atherosclerosis.
Journal Reference Authors Tall AR, Yvan-Charvet L
Title Cholesterol, inflammation and innate immunity.
Journal Reference Authors Kattoor AJ, Goel A, Mehta JL
Title LOX-1: Regulation, Signaling and Its Role in Atherosclerosis.
Journal Reference Authors Mehta JL, Li D
Title Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor.
Journal Reference Authors Li D, Mehta JL
Title Intracellular signaling of LOX-1 in endothelial cell apoptosis.
Journal Reference Authors Lubrano V, Balzan S
Title LOX-1 and ROS, inseparable factors in the process of endothelial damage.
Journal Reference Authors Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P
Title LOX-1 in atherosclerosis: biological functions and pharmacological modifiers.
Journal Reference Authors Mitra S, Goyal T, Mehta JL
Title Oxidized LDL, LOX-1 and atherosclerosis.
Journal Reference Authors Lu J, Mitra S, Wang X, Khaidakov M, Mehta JL
Title Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis.
Journal Reference Authors Ou HC, Song TY, Yeh YC, Huang CY, Yang SF, Chiu TH, Tsai KL, Chen KL, Wu YJ, Tsai CS, Chang LY, Kuo WW, Lee SD
Title EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling.
Journal Reference Authors Chen XP, Zhang TT, Du GH
Title Lectin-like oxidized low-density lipoprotein receptor-1, a new promising target for the therapy of atherosclerosis?
Journal Reference Authors Mattaliano MD, Wooters J, Shih HH, Paulsen JE
Title ROCK2 associates with lectin-like oxidized LDL receptor-1 and mediates oxidized LDL-induced IL-8 production.
Journal Reference Authors Salvador B, Arranz A, Francisco S, Cordoba L, Punzon C, Llamas MA, Fresno M
Title Modulation of endothelial function by Toll like receptors.
Journal Reference Authors Moore KJ, Sheedy FJ, Fisher EA
Title Macrophages in atherosclerosis: a dynamic balance.
Journal Reference Authors Butoi E, Gan AM, Manduteanu I
Title Molecular and functional interactions among monocytes/macrophages and smooth muscle cells and their relevance for atherosclerosis.
Journal Reference Authors Sheedy FJ, Moore KJ
Title IL-1 signaling in atherosclerosis: sibling rivalry.
Journal Reference Authors Moore KJ, Tabas I
Title Macrophages in the pathogenesis of atherosclerosis.
Journal Reference Authors Gui T, Shimokado A, Sun Y, Akasaka T, Muragaki Y
Title Diverse roles of macrophages in atherosclerosis: from inflammatory biology to biomarker discovery.
Journal Reference Authors Collot-Teixeira S, Martin J, McDermott-Roe C, Poston R, McGregor JL
Title CD36 and macrophages in atherosclerosis.
Journal Reference Authors Park YM, Febbraio M, Silverstein RL
Title CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima.
Journal Reference Authors Park YM
Title CD36, a scavenger receptor implicated in atherosclerosis.
Journal Reference Authors Seimon TA, Nadolski MJ, Liao X, Magallon J, Nguyen M, Feric NT, Koschinsky ML, Harkewicz R, Witztum JL, Tsimikas S, Golenbock D, Moore KJ, Tabas I
Title Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress.
Journal Reference Authors Nimgulkar C, Ghosh S, Sankar AB, Uday KP, Surekha MV, Madhusudhanachary P, Annapurna BR, Raghu P, Bharatraj DK
Title Combination of spices and herbal extract restores macrophage foam cell migration and abrogates the athero-inflammatory signalling cascade of atherogenesis.
Journal Reference Authors Canton J, Neculai D, Grinstein S
Title Scavenger receptors in homeostasis and immunity.
Journal Reference Authors Erridge C
Title The roles of Toll-like receptors in atherosclerosis.
Journal Reference Authors Seneviratne AN, Sivagurunathan B, Monaco C
Title Toll-like receptors and macrophage activation in atherosclerosis.
Journal Reference Authors Miller YI, Choi SH, Wiesner P, Fang L, Harkewicz R, Hartvigsen K, Boullier A, Gonen A, Diehl CJ, Que X, Montano E, Shaw PX, Tsimikas S, Binder CJ, Witztum JL
Title Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity.
Journal Reference Authors Tabas I
Title The role of endoplasmic reticulum stress in the progression of atherosclerosis.
Journal Reference Authors Grootaert MOJ, Moulis M, Roth L, Martinet W, Vindis C, Bennett MR, De Meyer GRY
Title Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis.
Journal Reference Authors Lipskaia L, Pourci ML, Delomenie C, Combettes L, Goudouneche D, Paul JL, Capiod T, Lompre AM
Title Phosphatidylinositol 3-kinase and calcium-activated transcription pathways are required for VLDL-induced smooth muscle cell proliferation.
Journal Reference Authors Cervantes Gracia K, Llanas-Cornejo D, Husi H
Title CVD and Oxidative Stress.
Journal Reference Authors Hansson GK, Hermansson A
Title The immune system in atherosclerosis.
Journal Reference Authors Roy H, Bhardwaj S, Yla-Herttuala S
Title Molecular genetics of atherosclerosis.
Journal Reference Authors Lusis AJ, Fogelman AM, Fonarow GC
Title Genetic basis of atherosclerosis: part I: new genes and pathways.
Journal Reference Authors Lusis AJ, Mar R, Pajukanta P
Title Genetics of atherosclerosis.
Journal Related ko04141 Protein processing in endoplasmic reticulum
ko04620 Toll-like receptor signaling pathway
ko04621 NOD-like receptor signaling pathway
ko04670 Leukocyte transendothelial migration
ko04975 Fat digestion and absorption
ko05418 Fluid shear stress and atherosclerosis
