Published online before print June 1, 2006, doi: 10.1161/01.STR.0000226901.34927.10
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2006;37:1923.)
© 2006 American Heart Association, Inc.
Progress Reviews |
Inflammation and Atherosclerosis
Novel Insights Into Plaque Formation and Destabilization
From the Departments of Neurology (G.S.) and Neuroradiology (M.B.), Julius-Maximilians-Universität, Würzburg, Germany.
Correspondence to Prof Dr Guido Stoll, Department of Neurology, Julius-Maximilians-Universität, Josef-Schneider-Str 11, D-Würzburg, Germany. E-mail stoll_g{at}klinik.uni-wuerzburg.de
Background and Purpose— The simplistic view of atherosclerosis as a disorder of pathological lipid deposition has been redefined by the more complex concept of an ongoing inflammatory response.
Summary of Review— Apolipoprotein E and low-density lipoprotein (LDL)-receptor-deficient mice develop accelerated atherosclerosis allowing in-depth pathophysiological investigations. Atherosclerotic plaques in these mice contain large numbers of T cells and macrophages. Crossbreading apolipoprotein E-deficient mice with T-cell-deficient mice and mice with impaired macrophage function (osteopetrotic op/op mice) disclosed the important impact of immune cells on atherosclerotic lesion development. In contrast to the detrimental role of T cells and macrophages, B cells appear to be atheroprotective. These basic experimental findings have partly been confirmed in studies of the human carotid artery system. Inflammation is not only instrumental in the development of human atheromatous plaques, but, importantly, plays a crucial role in the destabilization of internal carotid artery plaques, thus converting chronic atherosclerosis into an acute thrombo-embolic disorder. Humoral factors involved in internal carotid artery destabilization include cytokines, cyclooxygenase-2, matrix metalloproteinases, and tissue factor. Antibodies to oxidized LDL can reflect disease activity on one hand, but can also confer atheroprotection. Novel MRI techniques may aid in the in vivo assessment of acute plaque inflammation in humans.
Conclusions— The impact of inflammation on the development of atherosclerotic plaques and their destabilization opens new avenues for treatment. The effects of statins, acetylsalicyclic acid and angiotensin-converting enzyme inhibitors on stroke prevention may partly be attributable to their profound anti-inflammatory actions. Vaccination against modified LDL and heat shock proteins halt plaque progression in experimental atherosclerosis. Their potential for prevention of human atherosclerosis is currently under investigation.
Key Words: atherosclerosis • carotid artery • macrophages • T cells
This article has been cited by other articles:
 |
|
 |
|
  H. K. Takahashi, K. Liu, H. Wake, S. Mori, J. Zhang, R. Liu, T. Yoshino, and M. Nishibori Prostaglandin E2 Inhibits Advanced Glycation End Product-Induced Adhesion Molecule Expression, Cytokine Production, and Lymphocyte Proliferation in Human Peripheral Blood Mononuclear Cells J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 656 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wake, H. K. Takahashi, S. Mori, K. Liu, T. Yoshino, and M. Nishibori Histamine Inhibits Advanced Glycation End Products-Induced Adhesion Molecule Expression on Human Monocytes J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 826 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wu, Y. Shen, X. Liu, X. Ma, B. Xi, J. Mi, K. Lindpaintner, X. Tan, and X. Wang The 1425G/A SNP in PRKCH Is Associated With Ischemic Stroke and Cerebral Hemorrhage in a Chinese Population Stroke, September 1, 2009; 40(9): 2973 - 2976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Takahashi, S. Mori, H. Wake, K. Liu, T. Yoshino, K. Ohashi, N. Tanaka, K. Shikata, H. Makino, and M. Nishibori Advanced Glycation End Products Subspecies-Selectively Induce Adhesion Molecule Expression and Cytokine Production in Human Peripheral Blood Mononuclear Cells J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 89 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Diamond and S. Kaul Evidence-Based Financial Incentives for Healthcare Reform: Putting It Together Circ Cardiovasc Qual Outcomes, March 1, 2009; 2(2): 134 - 140. [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Swartz, S. S. Bhuta, R. I. Farb, R. Agid, R. A. Willinsky, K. G. terBrugge, J. Butany, B. A. Wasserman, D. M. Johnstone, F. L. Silver, et al. Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI Neurology, February 17, 2009; 72(7): 627 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sato, R. Kato, Y. Isogai, G.-i. Saka, M. Ohtsuki, Y. Taketomi, K. Yamamoto, K. Tsutsumi, J. Yamada, S. Masuda, et al. Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis J. Biol. Chem., November 28, 2008; 283(48): 33483 - 33497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Stoll, C. Kleinschnitz, and B. Nieswandt Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment Blood, November 1, 2008; 112(9): 3555 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Diamond and S. Kaul The Disconnect Between Practice Guidelines and Clinical Practice--Stressed Out JAMA, October 15, 2008; 300(15): 1817 - 1819. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Esmaillzadeh and L. Azadbakht Home use of vegetable oils, markers of systemic inflammation, and endothelial dysfunction among women Am. J. Clinical Nutrition, October 1, 2008; 88(4): 913 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Ho, T. T. Antoniv, J.-D. Ji, and L. B. Ivashkiv Lipopolysaccharide-Induced Expression of Matrix Metalloproteinases in Human Monocytes Is Suppressed by IFN-{gamma} via Superinduction of ATF-3 and Suppression of AP-1 J. Immunol., October 1, 2008; 181(7): 5089 - 5097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tichelli, J. Passweg, D. Wojcik, A. Rovo, J.-L. Harousseau, T. Masszi, A. Zander, A. Bekassy, C. Crawley, M. Arat, et al. Late cardiovascular events after allogeneic hematopoietic stem cell transplantation: a retrospective multicenter study of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation Haematologica, August 1, 2008; 93(8): 1203 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fortunato, M. D. Di Taranto, U. M. Bracale, L. Del Guercio, F. Carbone, C. Mazzaccara, A. Morgante, F. P. D'Armiento, M. D'Armiento, M. Porcellini, et al. Decreased Paraoxonase-2 Expression in Human Carotids During the Progression of Atherosclerosis Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 594 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Buck, D. S. Liebeskind, J. L. Saver, O. Y. Bang, S. W. Yun, S. Starkman, L. K. Ali, D. Kim, J. P. Villablanca, N. Salamon, et al. Early Neutrophilia Is Associated With Volume of Ischemic Tissue in Acute Stroke Stroke, February 1, 2008; 39(2): 355 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sen, A. Hinderliter, P. K. Sen, J. Simmons, V. A. LeGrys, J. Beck, S. Offenbacher, K. Moss, and S. M. Oppenheimer Association of Leukocyte Count With Progression of Aortic Atheroma in Stroke/Transient Ischemic Attack Patients Stroke, November 1, 2007; 38(11): 2900 - 2905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tichelli, C. Bucher, A. Rovo, G. Stussi, M. Stern, M. Paulussen, J. Halter, S. Meyer-Monard, D. Heim, D. A. Tsakiris, et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation Blood, November 1, 2007; 110(9): 3463 - 3471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li and H. E. Schellhorn New Developments and Novel Therapeutic Perspectives for Vitamin C J. Nutr., October 1, 2007; 137(10): 2171 - 2184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. C. Dupasquier, E. Dibrov, A. L. Kneesh, P. K. M. Cheung, K. G. Y. Lee, H. K. Alexander, B. K. Yeganeh, M. H. Moghadasian, and G. N. Pierce Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2394 - H2402. [Abstract] [Full Text] [PDF]
|
|