Arteriosklerose: Ätiologie und Pathogenese

Part of the Springer Reference Medizin book series (SRM)


Eine Schlüsselrolle in der Arteriosklerose-Entwicklung nimmt die arterielle Endothelzelle ein. In den letzten Jahren hat unser Wissen über die Endothelzellen beachtlich zugenommen, und insbesondere hat sich über die Endothelzellen eine kausale Verbindung zur Entzündung und zum metabolischen Syndrom ergeben. Die Arteriosklerose wird deswegen häufig als entzündliche Erkrankung der Endothelzellen verstanden. Dieses Verständnis hat die alte Zweiteilung in „Schädigungstheorie“ und „Fett-Theorie“ der Arteriosklerose durch ein umfassenderes Verständnis abgelöst. Endothelzellen, Entzündung und Blutgerinnung sind, wie wir heute wissen, verschiedene Bestandteile eines Systems. Am besten wird die große klinische Bedeutung dieses Systems durch die großen Erfolge derjenigen Bereiche der Pharmakotherapie der Arteriosklerose dokumentiert, die eine Hemmung der proinflammatorischen Reaktionen des Endothels und eine Hemmung der Blutgerinnung zum Ziel haben.


  1. Agarwal S (2009) The association of active and passive smoking with peripheral arterial disease: results from NHANES 1999–2004. Angiology 60:335–345 [Epub vor Druck]PubMedCrossRefGoogle Scholar
  2. Archer SL, Huang JM, Hampl V et al (1994) Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci U S A 91:7583–7587PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bapat SP, Myoung Suh J, Fang S, Liu S, Zhang Y, Cheng A, Zhou C, Liang Y, LeBlanc M, Liddle C, Atkins AR, Yu RT, Downes M, Evans RM, Zheng Y (2015) Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature 528:137–141PubMedPubMedCentralCrossRefGoogle Scholar
  4. Beasley JM, Ange BA, Anderson CA, Miller ER 3rd, Erlinger TP, Holbrook JT, Sacks FM, Appel LJ (2009) Associations between macronutrient intake and self-reported appetite and fasting levels of appetite hormones: results from the optimal macronutrient intake trial to prevent heart disease. Am J Epidemiol 169:893–900PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerle-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C (2007) MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 13:587–596PubMedCrossRefGoogle Scholar
  6. Boon RA, Horrevoets AJ (2009) Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie 29:39–40PubMedCrossRefGoogle Scholar
  7. Cerwinka WH, Cooper D, Krieglstein CF et al (2002) Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules. Am J Physiol Heart Circ Physiol 282:H1111–H1117PubMedCrossRefPubMedCentralGoogle Scholar
  8. Chelland Campbell S, Moffatt RJ, Stamford BA (2008) Smoking and smoking cessation – the relationship between cardiovascular disease and lipoprotein metabolism: a review. Atherosclerosis 201:225–235PubMedCrossRefGoogle Scholar
  9. Chen HW, Lii CK, Ku HJ, Wang TS (2009) Cigarette smoke extract induces expression of cell adhesion molecules in HUVEC via actin filament reorganization. Environ Mol Mutagen 50:96–104PubMedCrossRefGoogle Scholar
  10. Dai G, Kaazempur-Mofrad MR, Natarajan S, Zhang Y, Vaughn S, Blackman BR, Kamm RD, García-Cardeña G, Gimbrone MA Jr (2004) Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A 101:14871–14876PubMedPubMedCentralCrossRefGoogle Scholar
  11. Dai G, Vaughn S, Zhang Y, Wang ET, Garcia-Cardena G, Gimbrone MA Jr (2007) Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res 101:723–733PubMedCrossRefGoogle Scholar
  12. Deguchi J et al (2009) Genetically engineered resistance for MMP collagenases promotes abdominal aortic aneurysm formation in mice infused with angiotensin II. Lab Invest 89:315–326PubMedPubMedCentralCrossRefGoogle Scholar
  13. Dimmeler S, Zeiher AM (1999) Nitric oxide-an endothelial cell survival factor. Cell Death Differ 6:964–968PubMedCrossRefGoogle Scholar
  14. Elkind MS (2009) Inflammatory markers and stroke. Curr Cardiol Rep 11:12–20PubMedCrossRefGoogle Scholar
  15. Faggioli G, Ferri M, Rapezzi C, Tonon C, Manzoli L, Stella A (2009) Atherosclerotic aortic lesions increase the risk of cerebral embolism during carotid stenting in patients with complex aortic arch anatomy. J Vasc Surg 49:80–85PubMedCrossRefGoogle Scholar
  16. Foresta C, Caretta N, Corona G, Fabbri A, Francavilla S, Jannini E, Maggi M, Bettocchi C, Lenzi A (2009) Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart. Int J Androl 32(3):198–211PubMedCrossRefGoogle Scholar
  17. Gambaryan S, Kobsar A, Hartmann S et al (2008) NO-synthase-/NO-independent regulation of human and murine platelet soluble guanylyl cyclase activity. J Thromb Haemost 6:1376–1384PubMedCrossRefGoogle Scholar
  18. Geerts CC, Bots ML, Grobbee DE, Uiterwaal CS (2008) Parental smoking and vascular damage in young adult offspring: is early life exposure critical? The atherosclerosis risk in young adults study. Arterioscler Thromb Vasc Biol 28:2296–2302PubMedCrossRefGoogle Scholar
  19. Hellenthal FA, Geenen IL, Teijink JA, Heeneman S, Schurink GW (2008) Histological features of human abdominal aortic aneurysm are not related to clinical characteristics. Cardiovasc Pathol 18(5):286–293PubMedCrossRefGoogle Scholar
  20. Homme JL, Aubry MC, Edwards WD, Bagniewski SM, Shane Pankratz V, Kral CA, Tazelaar HD (2008) Surgical pathology of the ascending aorta: a clinicopathologic study of 513 cases. Am J Surg Pathol 30(9):1159–1168Google Scholar
  21. Kallio K et al (2009) Decreased aortic elasticity in healthy 11-year-old children exposed to tobacco smoke. Pediatrics 123(2):e267–e273PubMedCrossRefGoogle Scholar
  22. Kasashima S, Zen Y, Kawashima A, Konishi K, Sasaki H, Endo M, Matsumoto Y, Kawakami K, Kasashima F, Moriya M, Kimura K, Ohtake H, Nakanuma Y (2008) Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis. Am J Surg Pathol 32:197–204PubMedCrossRefGoogle Scholar
  23. Kasashima S, Zen Y, Kawashima A, Endo M, Matsumoto Y, Kasashima F (2009) A new clinicopathological entity of IgG4-related inflammatory abdominal aortic aneurysm. J Vasc Surg 49:1264–1271 [Epub vor Druck]PubMedCrossRefGoogle Scholar
  24. Keller G, Zimmer G, Mall G, Ritz E, Amann K (2003) Nephron number in patients with primary hypertension. N Engl J Med 348:101–108PubMedCrossRefGoogle Scholar
  25. Kimmelstiel P, Wilson C (1936) Benign and malignant hypertension and nephrosclerosis. A clinical and pathological study. Am J Pathol 12:45–48PubMedPubMedCentralGoogle Scholar
  26. Knoflach M et al (2009) Cardiovascular risk factors and atherosclerosis in young women. Atherosclerosis risk factors in female youngsters (ARFY study). Stroke 40:1063–1069 [Epub vor Druck]PubMedCrossRefGoogle Scholar
  27. Koenen RR, von Hundelshausen P, Nesmelova IV, Zernecke A, Liehn EA, Sarabi A, Kramp BK, Piccinini AM, Paludan SR, Kowalska MA, Kungl AJ, Hackeng TM, Mayo KH, Weber C (2009) Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nat Med 15:97–103PubMedCrossRefPubMedCentralGoogle Scholar
  28. Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655PubMedCrossRefPubMedCentralGoogle Scholar
  29. Lin Z, Kumar A, SenBanerjee S, Staniszewski K, Parmar K, Vaughan DE, Gimbrone MA Jr, Balasubramanian V, García-Cardeña G, Jain MK (2005) Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function. Circ Res 96:e48–e57PubMedCrossRefGoogle Scholar
  30. Ljungberg LU, Persson K (2008) Effect of nicotine and nicotine metabolites on angiotensin-converting enzyme in human endothelial cells. Endothelium 15:239–245PubMedCrossRefGoogle Scholar
  31. Ni M, Wang Y, Zhang M, Zhang PF, Ding SF, Liu CX, Liu XL, Zhao YX, Zhang Y (2009) Atherosclerotic plaque disruption induced by stress and lipopolysaccharide in apolipoprotein E knockout mice. Am J Physiol Heart Circ Physiol 296(5):H1598–H1606PubMedCrossRefGoogle Scholar
  32. Nishio E, Fukushima K, Shiozaki M et al (1996) Nitric oxide donor SNAP induces apoptosis in smooth muscle cells through cGMP-independent mechanism. Biochem Biophys Res Commun 221:163–168PubMedCrossRefGoogle Scholar
  33. Ohman MK, Shen Y, Obimba CI, Wright AP, Warnock M, Lawrence DA, Eitzman DT (2008) Visceral adipose tissue inflammation accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation 117:798–805PubMedPubMedCentralCrossRefGoogle Scholar
  34. Otsuka F, Byrne RA, Yahagi K, Mori H, Ladich E, Fowler DR, Kutys R, Xhepa E, Kastrati A, Virmani R, Joner M (2015) Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment. Eur Heart J 36(32):2147–2159., Epub 2015 May 20CrossRefPubMedPubMedCentralGoogle Scholar
  35. Pacifico L et al (2008) Nonalcoholic fatty liver disease and carotid atherosclerosis in children. Pediatr Res 63:423–427PubMedCrossRefGoogle Scholar
  36. Park YM, Febbraio M, Silverstein RL (2009) CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima. J Clin Invest 119:136–145PubMedGoogle Scholar
  37. Parmar KM, Nambudiri V, Dai G, Larman HB, Gimbrone MA Jr, García-Cardeña G (2005) Statins exert endothelial atheroprotective effects via the KLF2 transcription factor. J Biol Chem 280:26714–26719PubMedCrossRefGoogle Scholar
  38. Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET, Moorthy SN, Kratz JR, Lin Z, Jain MK, Gimbrone MA Jr, García-Cardeña G (2006) Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Invest 116:49–58PubMedCrossRefGoogle Scholar
  39. Ponnuswamy P, Ostermeier E, Schroettle A, Chen J, Huang PL, Ertl G, Nieswandt B, Kuhlencordt PJ (2009) Oxidative stress and compartment of gene expression determine proatherosclerotic effects of inducible nitric oxide synthase. Am J Pathol 174:2400–2410PubMedPubMedCentralCrossRefGoogle Scholar
  40. Radomski MW, Palmer RM, Moncada S (1987) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin. Br J Pharmacol 92(3):639–646PubMedPubMedCentralCrossRefGoogle Scholar
  41. Rapp JH, Pan XM, Neumann M, Hong M, Hollenbeck K, Liu J (2008) Microemboli composed of cholesterol crystals disrupt the blood-brain barrier and reduce cognition. Stroke 39:2354–2361PubMedCrossRefGoogle Scholar
  42. Sakata N, Tashiro T, Uesugi N, Kawara T, Furuya K, Hirata Y, Iwasaki H, Kojima M (2008) IgG4-positive plasma cells in inflammatory abdominal aortic aneurysm: the possibility of an aortic manifestation of IgG4-related sclerosing disease. Am J Surg Pathol 32:553–559PubMedCrossRefGoogle Scholar
  43. Sato Y, Hatakeyama K, Marutsuka K, Asada Y (2008) Incidence of asymptomatic coronary thrombosis and plaque disruption: comparison of non-cardiac and cardiac deaths among autopsy cases. Thromb Res 124(1):19–23PubMedCrossRefGoogle Scholar
  44. SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM, Kumar A, Feinberg MW, Chen Z, Simon DI, Luscinskas FW, Michel TM, Gimbrone MA Jr, García-Cardeña G, Jain MK (2004) KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med 199:1305–1315PubMedPubMedCentralCrossRefGoogle Scholar
  45. Shah PK (2009) Inflammation and plaque vulnerability. Cardiovasc Drugs Ther 23:31–40PubMedCrossRefGoogle Scholar
  46. Sommer G et al (2009) Secretory products form human adiocytes stimulate proinflammatory cytokine secretion from human endothelial cells. J Cell Biochem 106:729–737PubMedCrossRefGoogle Scholar
  47. Spalding KL et al (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787PubMedCrossRefGoogle Scholar
  48. Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, Mietus-Snyder ML, American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Nutrition, Physical Activity, and Metabolism (2009) Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 119:628–647PubMedCrossRefGoogle Scholar
  49. Tabas I (2009) Macrophage apoptosis in atherosclerosis: consequences on plaque progression and the role of endoplasmic reticulum stress. Antioxid Redox Signal 11(9):2333–2339PubMedPubMedCentralCrossRefGoogle Scholar
  50. Tousoulis D, Briasoulis A, Papageorgiou N, Antoniades C, Stefanadis C (2008) Candidate gene polymorphisms and the 9p21 locus in acute coronary syndromes. Trends Mol Med 14:441–449PubMedCrossRefGoogle Scholar
  51. Vaglio A, Greco P, Corradi D, Palmisano A, Martorana D, Ronda N, Buzio C (2006) Autoimmune aspects of chronic periaortitis. Autoimmun Rev 5:458–464PubMedCrossRefGoogle Scholar
  52. Wensveen FM, Valentić S, Šestan M, Turk Wensveen T, Polić B (2015) Interactions between adipose tissue and the immune system in health and malnutrition. Semin Immunol., pii: S1044-5323(15)00070-6CrossRefPubMedPubMedCentralGoogle Scholar
  53. Wilson AM, Cooke P (2007) L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 116:188–195PubMedCrossRefGoogle Scholar
  54. Yusuf K, Murat B, Unal A, Ulku K, Taylan K, Ozerdem O, Erdal Y, Tahsin Y (2007) Inflammatory abdominal aortic aneurysm: predictors of long-term outcome in a case-control study. Surgery 142:123 (Kommentar in Surgery 143: 300)Google Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2020

Authors and Affiliations

  1. 1.Pathologisches Institut der UniversitätLuitpoldkrankenhausWürzburgDeutschland
  2. 2.AngiologieAsklepios Klinik AltonaHamburgDeutschland

Personalised recommendations