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Abstract
Lipid accumulation in cells of subendothelial intima and the formation of foam cells is the earliest and the most noticeable manifestation of atherosclerosis at the cellular level. Generally, the foam cell formation is the result of interaction of cell with pro-atherogenic low-density lipoprotein providing cholesterol delivery and anti-atherogenic high-density lipoprotein providing its efflux. In this review, we discuss possible mechanisms of foam cell formation, the role of intracellular lipid deposition as a trigger of atherosclerotic lesion development, current approaches to diagnostics and strategies for preventing atherosclerosis based on recent knowledge of causes of foam cell formation.
Keywords
Atherogenesis
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atherosclerosis
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foam cells
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diagnostics
/
desialylation
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low-density lipoprotein
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subendothelial cells
/
therapy
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Alexander N. Orekhov, Veronika A. Myasoedova.
Low density lipoprotein-induced lipid accumulation is a key phenomenon of atherogenesis at the arterial cell level.
Vessel Plus, 2019, 3(1): 3 DOI:10.20517/2574-1209.2018.80
| [1] |
Sobenin IA,Grechko AV.Small dense and desialylated low density lipoprotein in diabetic patients..Vessel Plus2017;1:29-37
|
| [2] |
Alipov VI,Karagodin VP,Orekhov AN.Chemical composition of circulating native and desialylated low density lipoprotein: what is the difference?.Vessel Plus2017;1:107-15
|
| [3] |
Takahashi S.Triglyceride rich lipoprotein -LPL-VLDL receptor and Lp(a)-VLDL receptor pathways for macrophage foam cell formation..J Atheroscler Thromb2017;24:552-9 PMCID:PMC5453679
|
| [4] |
Lehti S,Belevich I,Heikkilä HM.Extracellular lipids accumulate in human carotid arteries as distinct three-dimensional structures and have proinflammatory properties..Am J Pathol2018;188:525-38
|
| [5] |
Orekhov AN,Bobryshev YV.Ruiz M.Naturally occurring multiple-modified low-density lipoprotein..Blood lipids and lipoproteins.2015;New YorkNova Science Publishers Inc.13-54
|
| [6] |
Allahverdian S,Boukais K,Bochaton-Piallat ML.Smooth muscle cell fate and plasticity in atherosclerosis..Cardiovasc Res2018;114:540-50 PMCID:PMC5852505
|
| [7] |
Kruth HS.Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam cell formation with native low-density lipoprotein particles..Curr Opin Lipidol2011;22:386-93 PMCID:PMC4174540
|
| [8] |
Kruth HS,Huang W,Ishii I.Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein..J Biol Chem2005;280:2352-60
|
| [9] |
Orekhov AN,Melnichenko AA.Circulating desialylated low density lipoprotein..Cor Vasa2017;59:e149-56
|
| [10] |
Orekhov AN.Modified lipoproteins as biomarkers of atherosclerosis..Front Biosci (Landmark Ed)2018;23:1422-44
|
| [11] |
Orekhov AN,Mukhin DN,Glukhova MA.Association of low-density lipoprotein with particulate connective tissue matrix components enhances cholesterol accumulation in cultured subendothelial cells of human aorta..Biochim Biophys Acta1987;928:251-8
|
| [12] |
Virella G,Elkes J,Rajab HA.Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human macrophages..Clin Immunol2018;187:1-9
|
| [13] |
Sánchez-Quesada JL,Ordóñez-Llanos J.Electronegative low-density lipoprotein. A link between apolipoprotein B misfolding, lipoprotein aggregation and proteoglycan binding..Curr Opin Lipidol2012;23:479-86
|
| [14] |
Orekhov AN,Bobryshev YV.Cellular mechanisms of human atherosclerosis: role of cell-to-cell communications in subendothelial cell functions..Tissue Cell2016;48:25-34
|
| [15] |
Orekhov AN,Nikiforov NG,Dubrovsky L.Modified LDL particles activate inflammatory pathways in monocyte-derived macrophages: transcriptome analysis..Curr Pharm Des2018;24:3143-51 PMCID:PMC6302360
|
| [16] |
Nègre-Salvayre A,Camaré C,Ferretti G.Dual signaling evoked by oxidized LDLs in vascular cells..Free Radic Biol Med2017;106:118-33
|
| [17] |
Jongstra-Bilen J,Wisnicki T,White-Alfred S.Oxidized low-density lipoprotein loading of macrophages downregulates TLR-Induced proinflammatory responses in a gene-specific and temporal manner through transcriptional control..J Immunol2017;199:2149-57
|
| [18] |
de la Paz Sánchez-Martínez M,Mora-Ruiz MD,Bernabe-García M.IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein..Lipids Health Dis2017;16:196 PMCID:PMC5634956
|
| [19] |
Orekhov AN.Cellular models of atherosclerosis and their implication for testing natural substances with anti-atherosclerotic potential..Phytomedicine2016;23:1190-7
|
| [20] |
Singh RK,Brumfield A,Bhardwaj P.Ceramide activation of RhoA/Rho kinase impairs actin polymerization during aggregated LDL catabolism..J Lipid Res2017;58:1977-87 PMCID:PMC5625121
|
| [21] |
Guo K,Xi D,Liu J.PSRC1 overexpression attenuates atherosclerosis progression in apoE(-/-) mice by modulating cholesterol transportation and inflammation..J Mol Cell Cardiol2018;116:69-80
|
| [22] |
Liu XX,Wang K,Ma WL.Kuwanon G attenuates atherosclerosis by upregulation of LXRα-ABCA1/ABCG1 and inhibition of NFκB activity in macrophages..Toxicol Appl Pharmacol2018;341:56-63
|
| [23] |
Ooi BK,Yap WH.Oxidative stress in cardiovascular diseases: involvement of Nrf2 antioxidant redox signaling in macrophage foam cells formation..Int J Mol Sci2017; PMCID:PMC5713305
|
| [24] |
Yang Y,Peng L,Sun N.Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway..Biochim Biophys Acta Mol Basis Dis2018;1864:882-90
|
| [25] |
Liu Z,Dai X,Ding Y.Macrophage liver kinase B1 inhibits foam cell formation and atherosclerosis..Circ Res2017;121:1047-57 PMCID:PMC5640502
|
| [26] |
Srikakulapu P,Rosenfeld SM,McSkimming C.Perivascular adipose tissue harbors atheroprotective IgM-producing B cells..Front Physiol2017;8:719 PMCID:PMC5609437
|
| [27] |
Srikakulapu P.B cells and atherosclerosis..Am J Physiol Heart Circ Physiol2017;312:H1060-7 PMCID:PMC5451581
|
| [28] |
Yan D,Dai J,Wang X.Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease foam cell formation..Biosci Rep2017; PMCID:PMC5479018
|
| [29] |
Maier A,Cordasic N,Dietel B.Hypoxia-inducible protein 2 Hig2/Hilpda mediates neutral lipid accumulation in macrophages and contributes to atherosclerosis in apolipoprotein E-deficient mice..FASEB J2017;31:4971-84
|
| [30] |
Chen L,Deng X,Yang X.Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI..Biochem Biophys Res Commun2017;491:587-94
|
| [31] |
Brotman DJ,Lauer MS.In search of fewer independent risk factors..Arch Intern Med2005;165:138-45
|
| [32] |
Stone NJ,Lichtenstein AH,Blum CB.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines..Circulation2014;129:S1-45
|
| [33] |
Catapano AL,De Backer G,Chapman MJ.2016 ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)..Atherosclerosis2016;253:281-344
|
| [34] |
Graham IM,Wong ND.Current guidelines on prevention with a focus on dyslipidemias..Cardiovasc Diagn Ther2017;7(Suppl 1):S4-10 PMCID:PMC5418212
|
| [35] |
Kooter AJ,Groenewold J,Sattar N.Integrating information from novel risk factors with calculated risks: the critical impact of risk factor prevalence..Circulation2011;124:741-5
|
| [36] |
Ioannidis JP.Minimal and null predictive effects for the most popular blood biomarkers of cardiovascular disease..Circ Res2012;110:658-62
|
| [37] |
Gilstrap LG.Biomarkers and cardiovascular risk assessment for primary prevention: an update..Clin Chem2012;58:72-82 PMCID:PMC4105324
|
| [38] |
Tzoulaki I,Evangelou E.Bias in associations of emerging biomarkers with cardiovascular disease..JAMA Intern Med2013;173:664-71
|
| [39] |
Orekhov AN,Kabakov AE,Pokrovsky SN.Autoantibodies against modified low density lipoprotein. Nonlipid factor of blood plasma that stimulates foam cell formation..Arterioscler Thromb1991;11:316-26
|
| [40] |
Tsimikas S.Oxidative modification of lipoproteins: mechanisms, role in inflammation and potential clinical applications in cardiovascular disease..Curr Pharm Des2011;17:27-37
|
| [41] |
Ivanova EA,Orekhov AN.LDL electronegativity index: a potential novel index for predicting cardiovascular disease..Vasc Health Risk Manag2015;11:525-32 PMCID:PMC4559248
|
| [42] |
Akyol S,Akyol O,Armutcu F.The role of electronegative low-density lipoprotein in cardiovascular diseases and its therapeutic implications..Trends Cardiovasc Med2017;27:239-46
|
| [43] |
Sobenin IA,Zhelankin AV,Kaikkonen J.Low density lipoprotein-containing circulating immune complexes: role in atherosclerosis and diagnostic value..Biomed Res Int2014;2014:205697 PMCID:PMC4087281
|
| [44] |
Sobenin IA,Melnichenko AC,Orekhov AN.Diagnostic and prognostic value of low density lipoprotein-containing circulating immune complexes in atherosclerosis..J Clin Immunol2013;33:489-95
|
| [45] |
Orekhov AN,Tertov VV.Lipoprotein immune complexes as markers of atherosclerosis..Int J Tissue React1991;13:233-6
|
| [46] |
Lopes-Virella MF,Lipsitz S,Wilson PF.Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes..Atherosclerosis2007;190:359-69
|
| [47] |
Lopes-Virella MF,Baker NL.High levels of AGE-LDL, and of IgG antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL in circulating immune complexes predict macroalbuminuria in patients with type 2 diabetes..J Diabetes Complications2016;30:693-9
|
| [48] |
Orekhov AN,Sobenin IA,Chistiakov DA.Modified low density lipoprotein and lipoprotein-containing circulating immune complexes as diagnostic and prognostic biomarkers of atherosclerosis and type 1 diabetes macrovascular disease..Int J Mol Sci2014;15:12807-41 PMCID:PMC4139876
|
| [49] |
Sobenin IA,Melnichenko AА,Orekhov AN.Low density lipoprotein-containing circulating immune complexes have better prognostic value in carotid intima-media thickness progression than other lipid parameters..Int J Cardiol2013;166:747-8
|
| [50] |
Leopold JA.Antioxidants and coronary artery disease: from pathophysiology to preventive therapy..Coron Artery Dis2015;26:176-83 PMCID:PMC4315737
|
| [51] |
American Heart Association Nutrition Committee,Appel LJ,Carnethon M.Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee..Circulation2006;114:82-96
|
| [52] |
Sampson UK,Linton MF.Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges..Curr Atheroscler Rep2012;14:1-10 PMCID:PMC3697085
|
| [53] |
Cholesterol Treatment Trialists’ (CTT) Collaboration,O’Connell R,Emberson J.Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials..Lancet2015;385:1397-405
|
| [54] |
Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study GroupPrevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels..N Engl J Med1998;339:1349-57
|
| [55] |
Heart Protection Study Collaborative GroupMRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial..Lancet2002;360:7-22
|
| [56] |
Downs JR,Weis S,Shapiro DR.Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study..JAMA1998;279:1615-22
|
| [57] |
Sacks FM,Moye LA,Rutherford JD.The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators..N Engl J Med1996;335:1001-9
|
| [58] |
Shepherd J,Ford I,Lorimer AR.Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group..N Engl J Med1995;333:1301-7
|
| [59] |
Cholesterol Treatment Trialists’ (CTT) CollaboratorsEfficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins..Lancet2005;366:1267-78
|
| [60] |
Chen Z,Collins R,Lu J.Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations..BMJ1991;303:276-82 PMCID:PMC1670480
|
| [61] |
Sacks FM,Shepherd J,Cobbe S.Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project..Circulation2000;102:1893-900
|
| [62] |
Kijani S,Levin M,Fogelstrand P.Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis..Physiol Rep2017; PMCID:PMC5532481
|
| [63] |
Borén J.The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity..Curr Opin Lipidol2016;27:473-83
|
| [64] |
Chistiakov DA,Revin VV,Bobryshev YV.The phenomenon of atherosclerosis reversal and regression: lessons from animal models..Exp Mol Pathol2017;102:138-45
|
| [65] |
Orekhov AN.Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention..Curr Pharm Des2013;19:5909-28
|
| [66] |
Zakiev ER,Orekhov AN.Cell-based models for development of antiatherosclerotic therapies..Biomed Res Int2017;2017:5198723 PMCID:PMC5329658
|
| [67] |
Orekhov AN,Novikov ID,Andreeva ER.Lipids in cells of atherosclerotic and uninvolved human aorta. I. Lipid composition of aortic tissue and enzyme isolated and cultured cells..Exp Mol Pathol1985;42:117-37
|
| [68] |
Orekhov AN,Kudryashov SA,Smirnov VN.Primary culture of human aortic intima cells as a model for testing antiatherosclerotic drugs. Effects of cyclic AMP, prostaglandins, calcium antagonists, antioxidants, and lipid-lowering agents..Atherosclerosis1986;60:101-10
|
| [69] |
Orekhov AN,Korneev NV,Myasoedova VA.Anti-atherosclerotic therapy based on botanicals..Recent Pat Cardiovasc Drug Discov2013;8:56-66 PMCID:PMC4637943
|
| [70] |
Kirichenko TV,Nikolic D,Orekhov AN.Anti-cytokine therapy for prevention of atherosclerosis..Phytomedicine2016;23:1198-210
|
| [71] |
Kirichenko TV,Orekhova VA,Nikitina NA.Phytoestrogen-rich natural preparation for treatment of climacteric syndrome and atherosclerosis prevention in perimenopausal women..Phytother Res2017;31:1209-14
|
| [72] |
Slevin M,Wang Q,Badimon L.Unique vascular protective properties of natural products: supplements or future main-line drugs with significant anti-atherosclerotic potential?.Vasc Cell2012;4:9 PMCID:PMC3508621
|
| [73] |
Orekhov AN.Modified and dysfunctional lipoproteins in atherosclerosis: effectors or biomarkers?.Curr Med Chem2018;
|