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 disease
BRITE hierarchy
Pathway map
Ortholog table
Disease
Orthology
K12473 low-density lipoprotein receptor
K08763 oxidised low-density lipoprotein receptor 1
K12330 Rho guanine nucleotide exchange factor 1
K01388 matrix metalloproteinase-1 (interstitial collagenase) [EC:3.4.24.7 ]
K04513 Ras homolog gene family, member A
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02159 apoptosis regulator BAX
K02158 Bcl-2-antagonist of cell death
K04570 Bcl-2-like 1 (apoptosis regulator Bcl-X)
K02161 apoptosis regulator Bcl-2
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K09364 POU domain transcription factor, class 2
K03160 tumor necrosis factor receptor superfamily member 5
K03161 tumor necrosis factor ligand superfamily member 5
K17683 cytochrome P450 family 2 subfamily A6 [EC:1.14.14.-]
K17709 cytochrome P450 family 2 subfamily B6 [EC:1.14.14.-]
K19722 receptor for advanced glycosylation end products
K21421 NADPH oxidase 2 [EC:1.-.-.-]
K08011 neutrophil cytosolic factor 1
K08009 cytochrome b-245, alpha polypeptide
K08010 neutrophil cytosolic factor 2
K08012 neutrophil cytosolic factor 4
K04392 Ras-related C3 botulinum toxin substrate 1
K04692 signal transducer and activator of transcription 3
K04393 cell division control protein 42
K04379 proto-oncogene protein c-fos
K04448 transcription factor AP-1
K06490 intercellular adhesion molecule 1
K04735 transcription factor p65
K02580 nuclear factor NF-kappa-B p105 subunit
K06494 selectin, endothelial cell
K06527 vascular cell adhesion molecule 1
K01394 matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17 ]
K04390 tumor necrosis factor receptor superfamily member 6
K03156 tumor necrosis factor superfamily, member 2
K03283 heat shock 70kDa protein 1/6/8
K26598 heat shock 70kDa protein 2
K09489 heat shock 70kDa protein 4
K04079 molecular chaperone HtpG
K09487 heat shock protein 90kDa beta
K05399 lipopolysaccharide-binding protein
K04391 monocyte differentiation antigen CD14
K05403 toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K04729 myeloid differentiation primary response protein MyD88
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734 NF-kappa-B inhibitor alpha
K05409 TRIF-related adaptor molecule
K05842 toll-like receptor adapter molecule 1
K03174 TNF receptor-associated factor 3
K12650 TRAF family member-associated NF-kappa-B activator
K07211 inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K09447 interferon regulatory factor 7
K05411 interferon regulatory factor 3
K08530 peroxisome proliferator-activated receptor gamma
K08524 retinoid X receptor alpha
K08525 retinoid X receptor beta
K08526 retinoid X receptor gamma
K05730 guanine nucleotide exchange factor VAV
K04353 Ras-related protein Rap-1A
K07836 Ras-related protein Rap-1B
K05505 C-X-C motif chemokine 1/2/3
K12800 NACHT, LRR and PYD domains-containing protein 3
K09054 cyclic AMP-dependent transcription factor ATF-6 alpha
K04452 DNA damage-inducible transcript 3
K10950 ERO1-like protein alpha [EC:1.8.4.-]
K04958 inositol 1,4,5-triphosphate receptor type 1
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K08860 eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1 ]
K03237 translation initiation factor 2 subunit 1
K04374 cyclic AMP-dependent transcription factor ATF-4
K08852 serine/threonine-protein kinase/endoribonuclease IRE1 [EC:2.7.11.1 3.1.26.-]
K09027 X box-binding protein 1
K05641 ATP-binding cassette, subfamily A (ABC1), member 1
K05679 ATP-binding cassette, subfamily G (WHITE), member 1
K05638 nuclear factor erythroid 2-related factor 2
K12799 apoptosis-associated speck-like protein containing a CARD
K20053 very low-density lipoprotein receptor
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K17333 nuclear factor of activated T-cells, cytoplasmic 3
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K06268 serine/threonine-protein phosphatase 2B regulatory subunit
K04721 tumor necrosis factor ligand superfamily member 10
K04722 tumor necrosis factor receptor superfamily member 10A/B
K03158 tumor necrosis factor receptor superfamily member 1A
K04389 tumor necrosis factor ligand superfamily member 6
K04726 BH3 interacting domain death agonist
K02084 apoptotic protease-activating factor
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
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
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