Abstract
Lipid metabolism plays an essential role in the pathogenesis of cardiovascular and metabolic diseases. Cholesteryl ester transfer protein (CETP) is a crucial glycoprotein involved in lipid metabolism by transferring cholesteryl esters (CE) and triglycerides (TG) between plasma lipoproteins. CETP activity results in reduced HDL-C and increased VLDL- and LDL-C concentrations, thus increasing the risk of cardiovascular and metabolic diseases. In this review, we discuss the structure of CETP and its mechanism of action. Furthermore, we focus on recent experiments on animal CETP-expressing models, deciphering the regulation and functions of CETP in various genetic backgrounds and interaction with different external factors. Finally, we discuss recent publications revealing the association of CETP single nucleotide polymorphisms (SNPs) with the risk of cardiovascular and metabolic diseases, lifestyle factors, diet and therapeutic interventions. While CETP SNPs can be used as effective diagnostic markers, diet, lifestyle, gender and ethnic specificity should also be considered for effective treatment.
[http://dx.doi.org/10.1016/0305-0491(82)90252-8] [PMID: 7060347]
[http://dx.doi.org/10.1016/j.bbalip.2016.01.016] [PMID: 26825693]
[http://dx.doi.org/10.1038/nsmb1197] [PMID: 17237796]
[http://dx.doi.org/10.1371/journal.pcbi.1002299]
[http://dx.doi.org/10.1038/nchembio.796] [PMID: 22344176]
[http://dx.doi.org/10.1074/jbc.M116.744623] [PMID: 27445332]
[http://dx.doi.org/10.1016/j.jsb.2016.02.016] [PMID: 26876146]
[http://dx.doi.org/10.1038/342448a0] [PMID: 2586614]
[http://dx.doi.org/10.1056/NEJM199011013231803] [PMID: 2215607]
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.09.035] [PMID: 30347344]
[http://dx.doi.org/10.1016/j.cca.2020.09.012] [PMID: 32941836]
[http://dx.doi.org/10.1007/s11883-023-01087-1] [PMID: 36881278]
[http://dx.doi.org/10.3390/ijms23052417] [PMID: 35269559]
[http://dx.doi.org/10.1007/s11883-022-01070-2] [PMID: 36409446]
[http://dx.doi.org/10.1097/MOL.0000000000000352] [PMID: 27676199]
[http://dx.doi.org/10.1194/jlr.R082735] [PMID: 29487091]
[http://dx.doi.org/10.1186/s12920-020-00760-7] [PMID: 32843070]
[http://dx.doi.org/10.1016/j.ophtha.2017.03.042] [PMID: 28456421]
[http://dx.doi.org/10.1001/jamacardio.2017.4177] [PMID: 29141072]
[http://dx.doi.org/10.1186/s12944-016-0394-1] [PMID: 28073362]
[http://dx.doi.org/10.1186/s12944-018-0888-0] [PMID: 30342531]
[http://dx.doi.org/10.1093/eurjpc/zwac290] [PMID: 36520639]
[http://dx.doi.org/10.1080/00365513.2016.1201849] [PMID: 27379467]
[http://dx.doi.org/10.1186/s12933-016-0428-z] [PMID: 27488210]
[http://dx.doi.org/10.1155/2017/1314864] [PMID: 28596970]
[http://dx.doi.org/10.1210/clinem/dgz119] [PMID: 31665383]
[http://dx.doi.org/10.1161/ATVBAHA.122.318004] [PMID: 35979837]
[http://dx.doi.org/10.3390/ijms23169417] [PMID: 36012684]
[http://dx.doi.org/10.1111/brv.12948] [PMID: 36880422]
[http://dx.doi.org/10.1016/j.drudis.2021.03.016] [PMID: 33781947]
[http://dx.doi.org/10.1016/j.bbalip.2021.159063] [PMID: 34637926]
[http://dx.doi.org/10.1186/s12944-016-0223-6] [PMID: 26984517]
[http://dx.doi.org/10.1111/eci.12770] [PMID: 28542805]
[http://dx.doi.org/10.1016/j.ajhg.2013.10.024] [PMID: 24507773]
[http://dx.doi.org/10.1002/jimd.12200] [PMID: 31800099]
[http://dx.doi.org/10.3390/nu12030610] [PMID: 32110925]
[PMID: 29371871]
[PMID: 30377591]
[http://dx.doi.org/10.1093/nutrit/nuab102] [PMID: 34957513]
[http://dx.doi.org/10.1007/s11745-017-4299-1] [PMID: 29058169]
[http://dx.doi.org/10.1038/364073a0] [PMID: 8316302]
[http://dx.doi.org/10.1161/01.ATV.19.4.1105] [PMID: 10195942]
[http://dx.doi.org/10.1074/jbc.274.52.36912] [PMID: 10601244]
[http://dx.doi.org/10.1038/s41440-020-0401-9] [PMID: 31974485]
[http://dx.doi.org/10.1016/0021-9150(93)90080-E] [PMID: 8257456]
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.10.108] [PMID: 26584136]
[http://dx.doi.org/10.3389/fphys.2018.00502] [PMID: 29867549]
[http://dx.doi.org/10.1016/j.metabol.2020.154429] [PMID: 33166579]
[http://dx.doi.org/10.1186/s12944-016-0179-6] [PMID: 26758205]
[http://dx.doi.org/10.14814/phy2.14732] [PMID: 33625789]
[http://dx.doi.org/10.1194/jlr.M069013] [PMID: 27354419]
[http://dx.doi.org/10.1016/j.molmet.2013.08.007] [PMID: 24327961]
[http://dx.doi.org/10.3389/fphys.2021.799096] [PMID: 35082691]
[http://dx.doi.org/10.1007/s13105-021-00834-9] [PMID: 34403126]
[http://dx.doi.org/10.2119/molmed.2011.00186] [PMID: 21953420]
[http://dx.doi.org/10.1016/j.jlr.2023.100365] [PMID: 37004910]
[http://dx.doi.org/10.1155/2017/3824276] [PMID: 29317793]
[http://dx.doi.org/10.1161/ATVBAHA.117.309114] [PMID: 28428219]
[http://dx.doi.org/10.1186/s12944-017-0563-x] [PMID: 28893253]
[http://dx.doi.org/10.3390/biom11010069] [PMID: 33430172]
[http://dx.doi.org/10.3390/antiox11091734] [PMID: 36139808]
[http://dx.doi.org/10.1016/S0021-9150(02)00327-1] [PMID: 12482565]
[http://dx.doi.org/10.1016/0021-9150(88)90094-9] [PMID: 3355618]
[http://dx.doi.org/10.1111/cge.12633] [PMID: 26126777]
[http://dx.doi.org/10.1017/S1368980020004863] [PMID: 33256881]
[http://dx.doi.org/10.1186/1471-2431-10-73] [PMID: 20937123]
[http://dx.doi.org/10.1001/jama.299.23.2777] [PMID: 18560005]
[http://dx.doi.org/10.1161/CIRCGENETICS.108.817304] [PMID: 20031564]
[http://dx.doi.org/10.1161/CIRCGENETICS.114.000748] [PMID: 25561046]
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311145] [PMID: 28506971]
[http://dx.doi.org/10.1016/j.jacc.2012.07.045] [PMID: 23083790]
[http://dx.doi.org/10.3390/ijerph13090882] [PMID: 27608031]
[http://dx.doi.org/10.1161/01.ATV.14.3.336] [PMID: 7907227]
[http://dx.doi.org/10.1093/nar/15.11.4698] [PMID: 2884631]
[http://dx.doi.org/10.1042/cs0790575] [PMID: 1980239]
[http://dx.doi.org/10.1111/j.1399-0004.1989.tb02904.x] [PMID: 2564326]
[http://dx.doi.org/10.1097/MD.0000000000013514] [PMID: 30544452]
[http://dx.doi.org/10.1186/s12872-020-01618-7] [PMID: 32682401]
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.01.024] [PMID: 28167353]
[http://dx.doi.org/10.17305/bjbms.2015.157] [PMID: 25725138]
[http://dx.doi.org/10.1002/lipd.12017] [PMID: 29570220]
[http://dx.doi.org/10.1093/labmed/lmz043] [PMID: 31504738]
[http://dx.doi.org/10.1093/labmed/lmw071] [PMID: 28387842]
[http://dx.doi.org/10.3390/biom9110739] [PMID: 31739638]
[http://dx.doi.org/10.1007/s10528-016-9782-5] [PMID: 27900488]
[http://dx.doi.org/10.1111/1755-5922.12302] [PMID: 28851085]
[http://dx.doi.org/10.21315/mjms2023.30.2.9] [PMID: 37102051]
[http://dx.doi.org/10.1111/jhn.12747] [PMID: 32163222]
[http://dx.doi.org/10.1159/000529053] [PMID: 36652934]
[http://dx.doi.org/10.1007/s10528-016-9766-5] [PMID: 27496123]
[http://dx.doi.org/10.1038/s41598-020-64031-2] [PMID: 32346024]
[http://dx.doi.org/10.1016/j.clnu.2016.12.024] [PMID: 28065481]
[http://dx.doi.org/10.34172/jcvtr.2020.32] [PMID: 33123324]
[http://dx.doi.org/10.1186/s12902-023-01391-6] [PMID: 37407953]
[http://dx.doi.org/10.1016/j.jcjd.2016.01.002] [PMID: 27590083]
[http://dx.doi.org/10.2217/fca-2018-0058] [PMID: 31148465]
[http://dx.doi.org/10.1186/s12933-018-0742-8] [PMID: 29973202]
[http://dx.doi.org/10.1038/s41598-021-95359-y] [PMID: 34354158]
[http://dx.doi.org/10.1194/jlr.M500051-JLR200] [PMID: 16106052]
[http://dx.doi.org/10.1016/S0022-2275(20)31511-X] [PMID: 11714854]
[PMID: 27429626]
[http://dx.doi.org/10.1186/s12877-016-0318-y] [PMID: 27439317]
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.06.020] [PMID: 30078763]
[http://dx.doi.org/10.1159/000507021] [PMID: 33105144]
[http://dx.doi.org/10.1038/s41430-019-0397-x] [PMID: 30705383]
[http://dx.doi.org/10.22038/ijbms.2018.26768.6555] [PMID: 29942448]
[http://dx.doi.org/10.1016/j.xhgg.2023.100204] [PMID: 37250494]
[http://dx.doi.org/10.1007/s12291-016-0585-6] [PMID: 28428701]
[http://dx.doi.org/10.18632/oncotarget.12898] [PMID: 27791990]
[http://dx.doi.org/10.1089/gtmb.2020.0012] [PMID: 32551884]
[http://dx.doi.org/10.1038/s41598-018-23074-2] [PMID: 29632305]
[http://dx.doi.org/10.1016/j.numecd.2020.10.019] [PMID: 33358712]
[http://dx.doi.org/10.21873/invivo.11540] [PMID: 31028198]
[http://dx.doi.org/10.12997/jla.2019.8.2.252] [PMID: 32821715]
[http://dx.doi.org/10.1016/j.endien.2018.07.002] [PMID: 29705571]
[http://dx.doi.org/10.1038/s41598-017-00102-1] [PMID: 28250428]
[http://dx.doi.org/10.1016/j.numecd.2018.02.018] [PMID: 29699816]
[http://dx.doi.org/10.1016/j.gene.2018.03.033] [PMID: 29548861]
[http://dx.doi.org/10.2337/dc16-0513] [PMID: 27457635]
[http://dx.doi.org/10.1186/1743-7075-10-26] [PMID: 23497168]
[http://dx.doi.org/10.1017/S0007114512002231] [PMID: 23021345]
[http://dx.doi.org/10.1016/j.jnutbio.2014.02.008] [PMID: 24746832]
[http://dx.doi.org/10.1371/journal.pone.0101688]
[http://dx.doi.org/10.2337/db18-0474] [PMID: 30213825]
[http://dx.doi.org/10.1016/j.clnu.2016.12.011] [PMID: 28057378]
[http://dx.doi.org/10.1194/jlr.P055715] [PMID: 25548261]
[http://dx.doi.org/10.2147/PGPM.S278671] [PMID: 33447072]
[http://dx.doi.org/10.1038/ng.271] [PMID: 19060910]
[http://dx.doi.org/10.1038/jhg.2015.170] [PMID: 26763881]
[http://dx.doi.org/10.1371/journal.pone.0218443]
[http://dx.doi.org/10.1371/journal.pone.0082420]
[http://dx.doi.org/10.1038/s10038-019-0591-7] [PMID: 30911093]
[http://dx.doi.org/10.1186/1471-2350-13-88] [PMID: 22994408]
[http://dx.doi.org/10.1194/jlr.P042077] [PMID: 24023260]
[http://dx.doi.org/10.3390/nu11051102] [PMID: 31108953]
[http://dx.doi.org/10.1016/j.atherosclerosis.2010.12.039] [PMID: 21292264]
[http://dx.doi.org/10.1034/j.1399-0004.2003.630104.x] [PMID: 12519368]
[http://dx.doi.org/10.1194/jlr.M045898] [PMID: 24847101]
[http://dx.doi.org/10.1089/ars.2015.6248] [PMID: 25606668]
[http://dx.doi.org/10.3390/biom9080321] [PMID: 31366177]
[http://dx.doi.org/10.3390/ijerph14060653] [PMID: 28629169]
[http://dx.doi.org/10.3390/ijms241210281] [PMID: 37373432]
[http://dx.doi.org/10.24875/ACM.21000039]
[http://dx.doi.org/10.1186/s12872-022-02695-6] [PMID: 35768776]
[http://dx.doi.org/10.1007/s11033-018-4342-1] [PMID: 30178218]
[http://dx.doi.org/10.1001/jamacardio.2021.3728] [PMID: 34613338]
[http://dx.doi.org/10.3390/biomedicines9030286] [PMID: 33799675]
[http://dx.doi.org/10.3906/sag-1510-92] [PMID: 28425253]
[http://dx.doi.org/10.1111/jth.14528] [PMID: 31148376]
[http://dx.doi.org/10.5551/jat.32201] [PMID: 27169917]
[http://dx.doi.org/10.3390/genes10100782] [PMID: 31597401]