Atherosclerosis is a potentially serious condition where arteries become clogged with fatty substances called plaques, or atheroma. These plaques cause the arteries to harden and narrow, restricting the blood flow and oxygen supply to vital organs, and increasing the risk of blood clots that could potentially block the flow of blood to the heart or brain. Atherosclerosis does not tend to have any symptoms at first and many people may be unaware they have it, but it can eventually cause life-threatening problems, such as heart attacks and strokes, if it gets worse. But the condition is largely preventable with a healthy lifestyle, and treatment can help reduce the risk of serious problems happening. If left to get worse, atherosclerosis can potentially lead to a number of serious conditions known as cardiovascular disease (CVD). There will not usually be any symptoms until CVD develops. Types of CVD include: Exactly why and how arteries become clogged is unclear. It can happen to anyone, although the following things can increase your risk: You cannot do anything about some of these factors, but by tackling things like an unhealthy diet and a lack of exercise you can help reduce your risk of atherosclerosis and CVD. Find out more about the risk factors for CVD Speak to your GP if you're worried you may be at a high risk of atherosclerosis. If you're between the ages of 40 and 74, you should have an NHS Health Check every 5 years, which will include tests to find out if you're at risk of atherosclerosis and CVD. Your GP or practice nurse can work out your level of risk by taking into account factors such as: Depending on your result, you may be advised to make lifestyle changes, consider taking medication or have further tests to check for atherosclerosis and CVD. Making healthy lifestyle changes can reduce your risk of developing atherosclerosis and may help stop it getting worse. The main ways you can reduce your risk are: Read more specific advice about preventing CVD There are not currently any treatments that can reverse atherosclerosis, but the healthy lifestyle changes suggested above may help stop it getting worse. Sometimes additional treatment to reduce the risk of problems like heart attacks and strokes may also be recommended, such as:
Page last reviewed: 02 May 2019
Next review due: 02 May 2022
1. Tamminen M, Mottino G, Qiao JH, Breslow JL, Frank JS. Ultrastructure of early lipid accumulation in apoE-deficient mice. Arterioscl. Thromb. Vasc. Biol. 1999;19:847–853. [PubMed] [Google Scholar]
2. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809. [PubMed] [Google Scholar]
3. Libby P. Changing concepts of atherogenesis. J. Intern. Med. 1999;247:349–358. [PubMed] [Google Scholar]
4. Mehrabian M, Wen P-Z, Fisler J, Davis RC, Lusis AJ. Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model. J. Clin. Invest. 1998;101:2485–2496. [PMC free article] [PubMed] [Google Scholar]
5. Lusis AJ, Weinreb A, Drake TA. In: Textbook of Cardiovascular Medicine. Topol EJ, editor. Lippincott-Raven; Philadelphia: 1998. pp. 2389–2413. [Google Scholar]
6. Goldbourt U, Neufeld HN. Genetic aspects of arteriosclerosis. Arteriosclerosis. 1988;6:357–377. [PubMed] [Google Scholar]
7. Smithies O, Maeda N. Gene targeting approaches to complex diseases: atherosclerosis and essential hypertension. Proc. Natl Acad. Sci. USA. 1995;92:5266–5272. [PMC free article] [PubMed] [Google Scholar]
8. Gimbrone MA., Jr Vascular endothelium, hemodynamic forces, and atherogenesis. Am. J. Pathol. 1999;155:1–5. [PMC free article] [PubMed] [Google Scholar]
9. Boren J, et al. Identification of the principal proteoglycan-binding site in LDL. A single-point mutation in apo-B100 severely affects proteoglycan interaction without affecting LDL receptor binding. J. Clin. Invest. 1998;101:2658–2664. [PMC free article] [PubMed] [Google Scholar]
10. Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC. Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein(a) mice. Nature. 1994;370:460–462. [PubMed] [Google Scholar]
11. Goldstein JL, Ho YK, Basu SK, Brown MS. Binding sites on macrophages that mediate uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc. Natl Acad. Sci. USA. 1979;76:333–337. [PMC free article] [PubMed] [Google Scholar]
12. Cyrus T, et al. Disruption of 12/15-lipoxygenase diminishes atherosclerosis in apoE-deficient mice. J. Clin. Invest. 1999;103:1597–1604. [PMC free article] [PubMed] [Google Scholar]
13. Hegele RA. Paraoxonase–genes and disease. Ann. Med. 1999;31:217–224. [PubMed] [Google Scholar]
14. Shih DM, et al. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J. Biol. Chem. 2000;276:17527–17535. [PubMed] [Google Scholar]
15. Watson AD, et al. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J. Biol. Chem. 1997;272:13597–13607. [PubMed] [Google Scholar]
16. Knowles JW, et al. Enhanced atherosclerosis and kidney dysfunction in eNOS(–/–) apoE(–/–) mice are ameliorated by enalapril treatment. J. Clin. Invest. 2000;105:451–458. [PMC free article] [PubMed] [Google Scholar]
17. Hofmann MA, et al. RAGE mediates a novel proinflammatory axis: a central surface receptor for S100/calgranulin polypeptides. Cell. 1999;97:889–901. [PubMed] [Google Scholar]
18. Dong ZM, et al. The combined role of P- and E-selectins in atherosclerosis. J. Clin. Invest. 1998;102:145–152. [PMC free article] [PubMed] [Google Scholar]
19. Collins RG, et al. P-selectin or intercellular adhesion molecule (ICAM-1) deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J. Exp. Med. 2000;191:189–194. [PMC free article] [PubMed] [Google Scholar]
20. Shih PT, et al. Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet. Circ. Res. 1998;84:345–351. [PubMed] [Google Scholar]
21. Gu L, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein-deficient mice. Mol. Cell. 1998;2:275–281. [PubMed] [Google Scholar]
22. Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2–/– mice reveals a role for chemokines in the initiation of atherosclerosis. Nature. 1998;394:894–897. [PubMed] [Google Scholar]
23. Smith JD, et al. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc. Natl Acad. Sci. USA. 1995;92:8264–8268. [PMC free article] [PubMed] [Google Scholar]
24. Podrez EA, et al. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J. Clin. Invest. 2000;105:1095–1108. [PMC free article] [PubMed] [Google Scholar]
25. Marathe S, Kuriakose G, Williams KJ, Tabas I. Sphingomyelinase, an enzyme implicated in atherogenesis, is present in atherosclerotic lesions and binds to specific components of the subendothelial extracellular matrix. Arterioscl. Thromb. Vasc. Biol. 1999;19:2648–2658. [PubMed] [Google Scholar]
26. Ivandic B, et al. Role of group II secretory phospholipase A2 in atherosclerosis I. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2. Arterioscl. Thromb. Vasc. Biol. 1999;19:1284–1290. [PubMed] [Google Scholar]
27. Suzuki H, et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997;386:292–296. [PubMed] [Google Scholar]
28. Febbraio M, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerosis lesion development in mice. J. Clin. Invest. 2000;105:1049–1056. [PMC free article] [PubMed] [Google Scholar]
29. Tontonoz P, Nagy L, Alvarez JL, Thomazy VA, Evans RM. PPAR gamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998;93:241–252. [PubMed] [Google Scholar]
30. Fazio S, et al. Increased atherogenesis in mice reconstituted with apolipoprotein E null macrophages. Proc. Natl Acad. Sci. USA. 1997;94:4647–4652. [PMC free article] [PubMed] [Google Scholar]
31. Accad M, et al. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1. J. Clin. Invest. 2000;105:711–719. [PMC free article] [PubMed] [Google Scholar]
32. Schönbeck U, Sukhova GK, Shimizu K, Mach F, Libby P. Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice. Proc. Natl Acad. Sci. USA. 2000;97:7458–7463. [PMC free article] [PubMed] [Google Scholar]
33. Fyfe AI, Qiao JH, Lusis AJ. Immune deficient mice develop typical atherosclerotic fatty streaks when fed an atherogenic diet. J. Clin. Invest. 1994;94:2516–2520. [PMC free article] [PubMed] [Google Scholar]
34. Shaw PX, et al. Natural antibodies with T15 idiotype may act in atherosclerosis apoptotic clearance and protective immunity. J. Clin. Invest. 2000;105:1731–1740. [PMC free article] [PubMed] [Google Scholar]
35. Gupta S, et al. IFN-γ potentiates atherosclerosis in apoE knock-out mice. J. Clin. Invest. 1997;99:2752–2761. [PMC free article] [PubMed] [Google Scholar]
36. Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr. Opin. Lipidol. 1999;10:417–429. [PubMed] [Google Scholar]
37. Negoro N, et al. Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy. J. Clin. Invest. 1995;95:1140–1150. [PMC free article] [PubMed] [Google Scholar]
38. Nathan L, Chaudhuri G. Estrogens and atherosclerosis. Annu. Rev. Pharmacol. Toxicol. 1997;37:477–515. [PubMed] [Google Scholar]
39. Streblow DN, et al. The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell. 1999;99:511–520. [PubMed] [Google Scholar]
40. Guevara NV, Kim H-S, Antonova EL, Chan L. The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo. Nature Med. 1999;5:335–339. [PubMed] [Google Scholar]
41. Schwartz SM, Murray CE. Proliferation and the monoclonal origin of atherosclerotic lesions. Annu. Rev. Med. 1998;49:437–460. [PubMed] [Google Scholar]
42. Watson KE, et al. TGF-β1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify. J. Clin. Invest. 1994;93:2106–2113. [PMC free article] [PubMed] [Google Scholar]
43. Moultan KS, Folkman J. In: Molecular Basis of Cardiovascular Disease. Chien KR, editor. Saunders; Philadelphia: 1999. pp. 393–410. [Google Scholar]
44. Schonbeck U, et al. CD40 ligation induces tissue factor expression in human vascular smooth muscle cells. Am. J. Pathol. 2000;156:7–14. [PMC free article] [PubMed] [Google Scholar]
45. Young SG, Fielding CJ. The ABCs of cholesterol efflux. Nature Genet. 1999;22:316–318. [PubMed] [Google Scholar]
46. Orsó E, et al. Transport of lipids from Golgi to plasma membrane is defective in Tangier disease patients and ABC1-deficient mice. Nature Genet. 2000;24:192–196. [PubMed] [Google Scholar]
47. Geller DS, et al. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000;289:119–123. [PubMed] [Google Scholar]
48. Cargill M, et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature Genet. 1999;22:231–238. [PubMed] [Google Scholar]
49. Krushkal J, et al. Genome-wide linkage analyses of systolic blood pressure using highly discordant siblings. Circulation. 1999;99:1407–1410. [PubMed] [Google Scholar]
50. Stoll M, et al. New target regions for human hypertension via comparative genomics. Genome Res. 2000;10:473–482. [PMC free article] [PubMed] [Google Scholar]
51. Aitman TJ, et al. Identification of CD36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nature Genet. 1999;21:76–83. [PubMed] [Google Scholar]
52. Shi W, Haberland ME, Jien ML, Shih DM, Lusis AJ. Endothelial responses to oxidized lipoproteins determine genetic susceptibility to atherosclerosis in mice. Circulation. 2000;102:75–81. [PubMed] [Google Scholar]
53. Risch NJ. Searching for genetic determinants in the new millennium. Nature. 2000;405:847–856. [PubMed] [Google Scholar]
54. Assmann G, Cullen P, Jossa F, Lewis B, Mancini M. Coronary heart disease: reducing the risk. Arterioscl. Thromb. Vasc. Biol. 1999;19:1819–1824. [PubMed] [Google Scholar]
55. Navab M, et al. The yin and the yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscl. Thromb. Vasc. Biol. 1996;16:831–842. [PubMed] [Google Scholar]
56. Desumont C, et al. Complete atherosclerosis regression after human apoE gene transfer in apoE deficient/nude mice. Arterioscl. Thromb. Vasc. Biol. 2000;20:435–442. [PubMed] [Google Scholar]
57. Herrera VL, et al. Spontaneous combined hyperlipidemia, coronary heart disease and decreased survival in Dahl salt-sensitive hypertensive rats transgenic for human cholesteryl ester transfer protein. Nature Med. 1999;5:1383–1389. [PubMed] [Google Scholar]
58. Gordon DJ, Rifkind BM. High-density lipoprotein—the clinical implications of recent studies. N. Engl. J. Med. 1989;321:1311–1316. [PubMed] [Google Scholar]
59. Kronenberg F, et al. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis. Circulation. 1999;100:1154–1160. [PubMed] [Google Scholar]
60. Luft FC. Molecular genetics of human hypertension. J. Hypertens. 1998;16:1871–1878. [PubMed] [Google Scholar]
61. Glassman AH, Shapiro PA. Depression and the course of coronary artery disease. Am. J. Psychiatry. 1998;155:4–11. [PubMed] [Google Scholar]
62. Kugiyama K, et al. Circulating levels of secretory type II phospholipase A2 predict coronary events in patients with coronary artery disease. Circulation. 1999;100:1280–1284. [PubMed] [Google Scholar]
63. Steinberg D, Witztum JL. In: Molecular Basis of Cardiovascular Disease. Chien KR, editor. Saunders; Philadelphia: 1999. pp. 458–475. [Google Scholar]
64. Hu H, Pierce GN, Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J. Clin. Invest. 1999;103:747–753. [PMC free article] [PubMed] [Google Scholar]
65. Cohen JC, Wang Z, Grundy SM, Stoesz MR, Guerra R. Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels. J. Clin. Invest. 1994;94:2377–2384. [PMC free article] [PubMed] [Google Scholar]
66. Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease: a meta-analysis. Circulation. 1999;99:2901–2907. [PubMed] [Google Scholar]
67. Samani NJ, Thompson JR, O’Toole L, Channer K, Woods KL. A meta-analysis of the association of the deletion allele of the antiogensin-converting enzyme gene with myocardial infarction. Circulation. 1996;94:708–712. [PubMed] [Google Scholar]
68. Tuomainen T-P, et al. Increased risk of acute myocardial infarction in carriers of the hemachromatosis gene Cys282 Tyr mutation. Circulation. 1999;100:1274–1279. [PubMed] [Google Scholar]
69. Hingorani AD, et al. A common variant of the endothelial nitric oxide synthase (Glu298 → Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999;100:1515–1520. [PubMed] [Google Scholar]
70. Franco RF, et al. Factor XIII and the risk of myocardial infarction. Haematologica. 2000;85:67–71. [PubMed] [Google Scholar]
71. Nievelstein-Post P, Mottino G, Fogelman A, Frank J. An ultrastructural study of lipoprotein accumulation in cardiac valves of the rabbit. Arterioscl. Thromb. Vasc. Biol. 1994;14:1151–1161. [PubMed] [Google Scholar]
72. Nievelstein PF, Fogelman AM, Mottino G, Frank JS. Lipid accumulation in rabbit aorta intima 2 hours after bolus infusion of low density lipoprotein. A deep-etch and immunolocalization study of ultrarapidly frozen tissue. Arterioscl. Thromb. Vasc. Biol. 1991;11:1795–1805. [PubMed] [Google Scholar]
Page 2
Complex lesions and thrombosis. Vulnerable plaques with thin fibrous caps result from degradation of matrix by various proteinases such as collagenases, gelatinases, stromolysin and cathepsins and by inhibition of matrix secretion. Among various factors that may destabilize plaques and promote thrombosis are infection, which may have systemic effects such as induction of acute phase proteins and local effects such as increased expression of tissue factor and decreased expression of plasminogen activator (PA). The calcification of lesions appears to be an active, regulated process involving the secretion by pericyte-like cells in the intima of a scaffold for calcium phosphate deposition. The formation of a thrombus, consisting of adherent platelets and fibrin crosslinks, usually results from plaque rupture, exposing tissue factor in the necrotic core.
Click on the image to see a larger version.