RGD Reference Report - Reverse cholesterol transport and cholesterol efflux in atherosclerosis. - Rat Genome Database

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Reverse cholesterol transport and cholesterol efflux in atherosclerosis.

Authors: Ohashi, R  Mu, H  Wang, X  Yao, Q  Chen, C 
Citation: Ohashi R, etal., QJM. 2005 Dec;98(12):845-56. Epub 2005 Oct 28.
RGD ID: 1600654
Pubmed: PMID:16258026   (View Abstract at PubMed)
DOI: DOI:10.1093/qjmed/hci136   (Journal Full-text)

Reverse cholesterol transport (RCT) is a pathway by which accumulated cholesterol is transported from the vessel wall to the liver for excretion, thus preventing atherosclerosis. Major constituents of RCT include acceptors such as high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I), and enzymes such as lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), hepatic lipase (HL) and cholesterol ester transfer protein (CETP). A critical part of RCT is cholesterol efflux, in which accumulated cholesterol is removed from macrophages in the subintima of the vessel wall by ATP-binding membrane cassette transporter A1 (ABCA1) or by other mechanisms, including passive diffusion, scavenger receptor B1 (SR-B1), caveolins and sterol 27-hydroxylase, and collected by HDL and apoA-I. Esterified cholesterol in the HDL is then delivered to the liver for excretion. In patients with mutated ABCA1 genes, RCT and cholesterol efflux are impaired and atherosclerosis is increased. In studies with transgenic mice, disruption of ABCA1 genes can induce atherosclerosis. Levels of HDL are inversely correlated with incidences of cardiovascular disease. Supplementation with HDL or apoA-I can reverse atherosclerosis by accelerating RCT and cholesterol efflux. On the other hand, pro-inflammatory factors such as interferon-gamma (IFN-gamma), endotoxin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), can be atherogenic by impairing RCT and cholesterol efflux, according to in vitro studies. RCT and cholesterol efflux play a major role in anti-atherogenesis, and modification of these processes may provide new therapeutic approaches to cardiovascular disease. Further research on new modifying factors for RCT and cholesterol efflux is warranted.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ABCA1Humanreverse cholesterol transport pathway  TAS  RGD 
APOA1Humanreverse cholesterol transport pathway  TAS  RGD 
Abca1Ratreverse cholesterol transport pathway  ISOABCA1 (Homo sapiens) RGD 
Abca1Mousereverse cholesterol transport pathway  ISOABCA1 (Homo sapiens) RGD 
Apoa1Ratreverse cholesterol transport pathway  ISOAPOA1 (Homo sapiens) RGD 
Apoa1Mousereverse cholesterol transport pathway  ISOAPOA1 (Homo sapiens) RGD 
CAV1Humanreverse cholesterol transport pathway  TAS  RGD 
CAV2Humanreverse cholesterol transport pathway  TAS  RGD 
CETPHumanreverse cholesterol transport pathway  TAS  RGD 
CYP27A1Humanreverse cholesterol transport pathway  TAS  RGD 
Cav1Ratreverse cholesterol transport pathway  ISOCAV1 (Homo sapiens) RGD 
Cav1Mousereverse cholesterol transport pathway  ISOCAV1 (Homo sapiens) RGD 
Cav2Ratreverse cholesterol transport pathway  ISOCAV2 (Homo sapiens) RGD 
Cav2Mousereverse cholesterol transport pathway  ISOCAV2 (Homo sapiens) RGD 
Cyp27a1Ratreverse cholesterol transport pathway  ISOCYP27A1 (Homo sapiens) RGD 
Cyp27a1Mousereverse cholesterol transport pathway  ISOCYP27A1 (Homo sapiens) RGD 
LCATHumanreverse cholesterol transport pathway  TAS  RGD 
LIPCHumanreverse cholesterol transport pathway  TAS  RGD 
LcatRatreverse cholesterol transport pathway  ISOLCAT (Homo sapiens) RGD 
LcatMousereverse cholesterol transport pathway  ISOLCAT (Homo sapiens) RGD 
LipcRatreverse cholesterol transport pathway  ISOLIPC (Homo sapiens) RGD 
LipcMousereverse cholesterol transport pathway  ISOLIPC (Homo sapiens) RGD 
PLTPHumanreverse cholesterol transport pathway  TAS  RGD 
PltpRatreverse cholesterol transport pathway  ISOPLTP (Homo sapiens) RGD 
PltpMousereverse cholesterol transport pathway  ISOPLTP (Homo sapiens) RGD 
SCARB1Humanreverse cholesterol transport pathway  TAS  RGD 
Scarb1Ratreverse cholesterol transport pathway  ISOSCARB1 (Homo sapiens) RGD 
Scarb1Mousereverse cholesterol transport pathway  ISOSCARB1 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Abca1  (ATP binding cassette subfamily A member 1)
Apoa1  (apolipoprotein A1)
Cav1  (caveolin 1)
Cav2  (caveolin 2)
Cyp27a1  (cytochrome P450, family 27, subfamily a, polypeptide 1)
Lcat  (lecithin cholesterol acyltransferase)
Lipc  (lipase C, hepatic type)
Pltp  (phospholipid transfer protein)
Scarb1  (scavenger receptor class B, member 1)

Genes (Mus musculus)
Abca1  (ATP-binding cassette, sub-family A member 1)
Apoa1  (apolipoprotein A-I)
Cav1  (caveolin 1, caveolae protein)
Cav2  (caveolin 2)
Cyp27a1  (cytochrome P450, family 27, subfamily a, polypeptide 1)
Lcat  (lecithin cholesterol acyltransferase)
Lipc  (lipase, hepatic)
Pltp  (phospholipid transfer protein)
Scarb1  (scavenger receptor class B, member 1)

Genes (Homo sapiens)
ABCA1  (ATP binding cassette subfamily A member 1)
APOA1  (apolipoprotein A1)
CAV1  (caveolin 1)
CAV2  (caveolin 2)
CETP  (cholesteryl ester transfer protein)
CYP27A1  (cytochrome P450 family 27 subfamily A member 1)
LCAT  (lecithin-cholesterol acyltransferase)
LIPC  (lipase C, hepatic type)
PLTP  (phospholipid transfer protein)
SCARB1  (scavenger receptor class B member 1)


Additional Information