Entry
Name
Lipid and atherosclerosis - Homo sapiens (human)
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 disease
BRITE hierarchy
Pathway map
Ortholog table
Disease
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
3949 LDLR; low density lipoprotein receptor [KO:K12473 ]
4973 OLR1; oxidized low density lipoprotein receptor 1 [KO:K08763 ]
9138 ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330 ]
387 RHOA; ras homolog family member A [KO:K04513 ]
9475 ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388 ] [EC:2.7.11.1 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159 ]
572 BAD; BCL2 associated agonist of cell death [KO:K02158 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
1548 CYP2A6; cytochrome P450 family 2 subfamily A member 6 [KO:K17683 ] [EC:1.14.14.-]
1549 CYP2A7; cytochrome P450 family 2 subfamily A member 7 [KO:K17683 ] [EC:1.14.14.-]
1555 CYP2B6; cytochrome P450 family 2 subfamily B member 6 [KO:K17709 ] [EC:1.14.14.-]
177 AGER; advanced glycosylation end-product specific receptor [KO:K19722 ]
1536 CYBB; cytochrome b-245 beta chain [KO:K21421 ] [EC:1.-.-.-]
1535 CYBA; cytochrome b-245 alpha chain [KO:K08009 ]
4688 NCF2; neutrophil cytosolic factor 2 [KO:K08010 ]
4689 NCF4; neutrophil cytosolic factor 4 [KO:K08012 ]
6774 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
998 CDC42; cell division cycle 42 [KO:K04393 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
6347 CCL2; C-C motif chemokine ligand 2 [KO:K14624 ]
3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
7412 VCAM1; vascular cell adhesion molecule 1 [KO:K06527 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
3312 HSPA8; heat shock protein family A (Hsp70) member 8 [KO:K03283 ]
3303 HSPA1A; heat shock protein family A (Hsp70) member 1A [KO:K03283 ]
3305 HSPA1L; heat shock protein family A (Hsp70) member 1 like [KO:K03283 ]
3304 HSPA1B; heat shock protein family A (Hsp70) member 1B [KO:K03283 ]
3310 HSPA6; heat shock protein family A (Hsp70) member 6 [KO:K03283 ]
3306 HSPA2; heat shock protein family A (Hsp70) member 2 [KO:K26598 ]
3308 HSPA4; heat shock protein family A (Hsp70) member 4 [KO:K09489 ]
3320 HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079 ]
3326 HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079 ]
7184 HSP90B1; heat shock protein 90 beta family member 1 [KO:K09487 ]
3929 LBP; lipopolysaccharide binding protein [KO:K05399 ]
114609 TIRAP; TIR domain containing adaptor protein [KO:K05403 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
353376 TICAM2; TIR domain containing adaptor molecule 2 [KO:K05409 ]
148022 TICAM1; TIR domain containing adaptor molecule 1 [KO:K05842 ]
7187 TRAF3; TNF receptor associated factor 3 [KO:K03174 ]
10010 TANK; TRAF family member associated NFKB activator [KO:K12650 ]
9641 IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211 ] [EC:2.7.11.10 ]
3665 IRF7; interferon regulatory factor 7 [KO:K09447 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
948 CD36; CD36 molecule (CD36 blood group) [KO:K06259 ]
5468 PPARG; peroxisome proliferator activated receptor gamma [KO:K08530 ]
10451 VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730 ]
7409 VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730 ]
7410 VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730 ]
5906 RAP1A; RAP1A, member of RAS oncogene family [KO:K04353 ]
5908 RAP1B; RAP1B, member of RAS oncogene family [KO:K07836 ]
6352 CCL5; C-C motif chemokine ligand 5 [KO:K12499 ]
6348 CCL3; C-C motif chemokine ligand 3 [KO:K05408 ]
6349 CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408 ]
414062 CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408 ]
2919 CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505 ]
2920 CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505 ]
2921 CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505 ]
114548 NLRP3; NLR family pyrin domain containing 3 [KO:K12800 ]
22926 ATF6; activating transcription factor 6 [KO:K09054 ]
1649 DDIT3; DNA damage inducible transcript 3 [KO:K04452 ]
30001 ERO1A; endoplasmic reticulum oxidoreductase 1 alpha [KO:K10950 ] [EC:1.8.4.-]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515 ] [EC:2.7.11.17 ]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515 ] [EC:2.7.11.17 ]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515 ] [EC:2.7.11.17 ]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515 ] [EC:2.7.11.17 ]
9451 EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860 ] [EC:2.7.11.1 ]
1965 EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
2081 ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852 ] [EC:2.7.11.1 3.1.26.-]
19 ABCA1; ATP binding cassette subfamily A member 1 [KO:K05641 ]
9619 ABCG1; ATP binding cassette subfamily G member 1 [KO:K05679 ]
4780 NFE2L2; NFE2 like bZIP transcription factor 2 [KO:K05638 ]
29108 PYCARD; PYD and CARD domain containing [KO:K12799 ]
7436 VLDLR; very low density lipoprotein receptor [KO:K20053 ]
4772 NFATC1; nuclear factor of activated T cells 1 [KO:K04446 ]
4773 NFATC2; nuclear factor of activated T cells 2 [KO:K17332 ]
4775 NFATC3; nuclear factor of activated T cells 3 [KO:K17333 ]
5534 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
5535 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
8743 TNFSF10; TNF superfamily member 10 [KO:K04721 ]
8797 TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722 ]
8795 TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722 ]
7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158 ]
637 BID; BH3 interacting domain death agonist [KO:K04726 ]
317 APAF1; apoptotic peptidase activating factor 1 [KO:K02084 ]
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 pathway
hsa04141 Protein processing in endoplasmic reticulum
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04670 Leukocyte transendothelial migration
hsa05418 Fluid shear stress and atherosclerosis
KO pathway
LinkDB
All DBs