Pathobiology of Atherosclerosis-a Brief Review

 

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ABSTRACT

Considerable progress has been made recently in understanding the pathobiology of atherosclerosis. To a significant degree it is an inflammatory disease of the vessel wall. Progression of atherosclerosis or its stabilization reflects the tension between cytokines and effectors that play both an inhibiting and a facilitating role in the progression of atherosclerosis, including platelet-derived growth factor (PDGF), interleukin-1, tumor necrosis factor (TNF) -α, and MCP-1. The response to injury model remains central to our understanding of atherogenesis. Numerous factors may initiate endothelial injury, including mechanical factors (hypertension and high shear stress in the artery), homocysteine, oxidized low-density lipoprotein (LDL), possibly infectious agents such as Chlamydia, viruses, and toxins such as nicotine. These factors lead to endothelial cells' increasing expression of receptors for LDL and increased adherence of monocytes and macrophages and T cells. Progression of atherosclerosis can lead to the development of a plaque that is vulnerable to rupture and that would then produce an acute coronary syndrome. In addition to standard biomarkers and angiographic approaches for detecting plaque rupture, novel diagnostic approaches are under development, including near infrared spectroscopy, catheter-based thermography, and optical coherence tomography. Our better understanding of the atherosclerotic plaque provides multiple opportunities for interdicting arterial injury, and the response to it.

REFERENCES

• 1 Ross R. The pathogenesis of atherosclerosis. In: Braunwald E Heart Disease, 5th ed Philadelphia; WB Saunders 1997: 1105-1125
  Google Scholar
• 2 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990's.  Nature. 1993;  362 801-805
  CrossrefPubMedGoogle Scholar
• 3 Fuster V, Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology.  Circulation. 1994;  90 2126-2146
  CrossrefPubMedGoogle Scholar
• 4 Corti R, Fuster V, Badimon J J. Pathogenetic concepts of acute coronary syndromes.  J Am Coll Cardiol. 2003;  41 7S-14S
  CrossrefPubMedGoogle Scholar
• 5 Falk E, Shah P K, Fuster V. Coronary plaque disruption.  Circulation. 1995;  92 657-671
  CrossrefPubMedGoogle Scholar
• 6 Fishbein M, Siegal R J. How big are coronary atherosclerotic plaques that rupture?.  Circulation. 1996;  94 2662-2666
  PubMedGoogle Scholar
• 7 Aikawa M, Sugiyama S, Hill C C et al.. Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit atheroma.  Circulation. 2002;  106 1390-1396
  CrossrefPubMedGoogle Scholar
• 8 Libby P. Inflammation in atherosclerosis.  Nature. 2002;  420 868-874
  CrossrefPubMedGoogle Scholar
• 9 Ridker P M, Rifai N, Rose L, Buring J E, Cook N R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cadiovascular events.  N Engl J Med. 2002;  347 1557-1565
  CrossrefPubMedGoogle Scholar
• 10 Buffon A, Biasucci L M, Liuzzo G et al.. Widespread coronary inflammation in unstable angina.  N Engl J Med. 2002;  347 5-12
  CrossrefPubMedGoogle Scholar
• 11 Heeschen C, Dimmeler S, Hamm C W et al.. Soluble CD40 ligand in acute coronary syndromes.  N Engl J Med. 2003;  348 1104-1111
  CrossrefPubMedGoogle Scholar
• 12 Mach F, Schonbeck U, Bonnefoy J Y, Pober J S, Libby P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor.  Circulation. 1997;  96 396-399
  PubMedGoogle Scholar
• 13 Urbich C, Mallat Z, Tedgui A et al.. Upregulation of TRAF-3 by shear stress blocks CD40-mediated endothelial activation.  J Clin Invest. 2001;  108 1451-1458
  CrossrefPubMedGoogle Scholar
• 14 Andre P, Prasad K S, Denis C V et al.. CD40L stabilizes arterial thrombi by a beta3 integrin-dependent mechanism.  Nat Med. 2002;  8 247-252
  PubMedGoogle Scholar
• 15 Varo N, Vicent D, Libby P et al.. Elevated plasma levels of the atherogenic mediator soluble CD40 ligand in diabetic patients a novel target of thiazolidinediones.  Circulation. 2003;  107 2664-2669
  CrossrefPubMedGoogle Scholar
• 16 Davies M J, Thomas A C. Plaque fissuring: the cause of acute myocardial infarction, sudden ischemic death and crescendo angina.  Br Heart J. 1985;  53 363-373
  CrossrefPubMedGoogle Scholar
• 17 Burrig K F. The endothelium of advanced arteriosclerotic plaques in humans.  Arterioscler Thromb. 1991;  11 1678-1689
  PubMedGoogle Scholar
• 18 Libby P. Molecular basis of acute coronary syndromes.  Circulation. 1995;  91 2844-2850
  CrossrefPubMedGoogle Scholar
• 19 Hangartner J R, Charleston A J, Davies M J, Thomas A C. Morphological characteristics of clinically significant coronary artery stenosis in stable angina.  Br Heart J. 1986;  56 501-508
  PubMedGoogle Scholar
• 20 Davies M, Woolf N, Rowles P, Richardson P. Lipid and celllular constituents of unstable human aortic plaque.  Basic Research in Cardiology. 1994;  89(Supp1) 11-39
  PubMedGoogle Scholar
• 21 Rioufol G, Finet G, Ginon I et al.. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study.  Circulation. 2002;  106 804-808
  CrossrefPubMedGoogle Scholar
• 22 Burke A P, Farb A, Malcom G T et al.. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly.  N Engl J Med. 1997;  336 1276-1282
  CrossrefPubMedGoogle Scholar
• 23 Zairis M, Papadaki O, Manousakis S et al.. C-reactive protein and multiple complex coronary artery plaques in patients with primary unstable angina.  Atherosclerosis. 2002;  164 355-359
  CrossrefPubMedGoogle Scholar
• 24 Casscells W, Hathorn B, David M et al.. Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis.  Lancet. 1996;  347 1447-1451
  CrossrefPubMedGoogle Scholar
• 25 Naghavi M, Madjid M, Khan M R et al.. New developments in the detection of vulnerable plaque.  Curr Atheroscler Rep. 2001;  3 125-135
  PubMedGoogle Scholar
• 26 Komiyama N, Berry G J, Kolz M L et al.. Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries.  Am Heart J. 2000;  140 565-574
  CrossrefPubMedGoogle Scholar
• 27 Thieme T, Wernecke K D, Meyer R et al.. Angioscopic evaluation of atherosclerotic plaques: validation by histomorphologic analysis and association with stable and unstable coronary syndromes.  J Am Coll Cardiol. 1996;  28 1-6
  CrossrefPubMedGoogle Scholar
• 28 Stefanadis C, Diamantopoulos L, Vlachapoulos C et al.. Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: a new method of detection by application of a special thermography catheter.  Circulation. 1999;  99 1965-1971
  PubMedGoogle Scholar
• 29 Moreno P, Lodder R, Purushothaman K et al.. Detection of lipid pool, thin fibrous cap, and inflammatory cells in human aortic atherosclerotic plaques by near-infrared spectroscopy.  Circulation. 2002;  105 923-927
  CrossrefPubMedGoogle Scholar

James D MarshM.D. 

Department of Internal Medicine, University of Arkansas for Medical Sciences

4301 W. Markham #610, Little Rock, AR 72205

Email: JDMarsh@UAMS.edu