Abstract
Abdominal aortic aneurysms (AAA) are permanent dilations in the infra-renal area in which the arterial tissue is characterized by inflammation and medial degeneration. AAAs are a common vascular disorder and cause significant mortality in the aged population. Despite the high prevalence of this disease, there is limited knowledge on the mechanisms responsible for the vascular pathology. Therefore, current therapeutic options are restricted to surgical intervention and are predicated on the assumed propensity for rupture as the vessel enlarges. Current research focuses on inflammatory processes and their role in proteolytic degradation of the elastin and collagen fibers of the vessel wall. Definition of specific mechanisms would identify target sites for potential pharmacologic intervention and markedly improve the medical treatment and prognosis of AAA.
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Bengtsson H, Sonesson B, Bergqvist D: Incidence and prevalence of abdominal aortic aneurysms, estimated by necropsy studies and population screening by ultrasound. Ann NY Acad Sci 1996, 800:1–24.
Hallett JW Jr: Management of abdominal aortic aneurysms. Mayo Clin Proc 2000, 75:395–399.
Hallin A, Bergqvist D, Holmberg L: Literature review of surgical management of abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2001, 22:197–204.
Thompson MM, Bell PR: ABC of arterial and venous disease. Arterial aneurysms. BMJ 2000, 320:1193–1196.
UK Small Aneurysm Trial Participants: Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet 1998, 352:1649–1655.
Johnston KW, Rutherford RB, Tilson MD, et al.: Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 1991, 13:452–458.
Thompson RW, Baxter BT: MMP inhibition in abdominal aortic aneurysms. Rationale for a prospective randomized clinical trial. Ann NY Acad Sci 1999, 878:159–178.
Wilmink AB, Quick CR: Epidemiology and potential for prevention of abdominal aortic aneurysm. Br J Surg 1998, 85:155–162.
Wassef M, Baxter BT, Chisholm RL, et al.: Pathogenesis of abdominal aortic aneurysms: a multidisciplinary research program supported by the National Heart, Lung, and Blood Institute. J Vasc Surg 2001, 34:730–738.
Lopez-Candales A, Holmes DR, Liao SX, et al.: Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms. Am J Pathol 1997, 150:993–1007.
Freestone T, Turner RJ, Coady A, et al.: Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 1995, 15:1145–1151.
Shah PK: Inflammation, metalloproteinases, and increased proteolysis: an emerging pathophysiological paradigm in aortic aneurysm. Circulation 1997, 96:2115–2117.
Xu CP, Zarins CK, Glagov S: Aneurysmal and occlusive atherosclerosis of the human abdominal aorta. J Vasc Surg 2001, 33:91–96.
Reed D, Reed C, Stemmermann G, et al.: Are aortic aneurysms caused by atherosclerosis? Circulation 1992, 85:205–211.
Tilson MD: Aortic aneurysms and atherosclerosis. Circulation 1992, 85:378–379.
Koch AE, Haines GK, Rizzo RJ, et al.: Human abdominal aortic aneurysms. Immunophenotypic analysis suggesting an immune-mediated response. Am J Pathol 1990, 137:1199–1213.
Anidjar S, Dobrin PB, Eichorst M, et al.: Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms. J Vasc Surg 1992, 16:139–147.
Ozsvath KJ, Hirose H, Xia S, et al.: Expression of two novel recombinant proteins from aortic adventitia (kappafibs) sharing amino acid sequences with cytomegalovirus. J Surg Res 1997, 69:277–282.
Koch AE, Kunkel SL, Pearce WH, et al.: Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms. Am J Pathol 1993, 142:1423–1431.
Pearce WH, Sweis I, Yao JS, et al.: Interleukin-1 beta and tumor necrosis factor-alpha release in normal and diseased human infrarenal aortas. J Vasc Surg 1992, 16:784–789.
Szekanecz Z, Shah MR, Pearce WH, et al.: Human atherosclerotic abdominal aortic aneurysms produce interleukin (IL)-6 and interferon-gamma but not IL-2 and IL-4: the possible role for IL-6 and interferon-gamma in vascular inflammation. Agents Actions 1994, 42:159–162.
Juvonen J, Surcel HM, Satta J, et al.: Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 1997, 17:2843–2847.
Rohde LE, Arroyo LH, Rifai N, et al.: Plasma concentrations of interleukin-6 and abdominal aortic diameter among subjects without aortic dilatation. Arterioscler Thromb Vasc Biol 1999, 19:1695–1699.
Jones KG, Brull DJ, Brown LC, et al.: Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation 2001, 103:2260–2265.
Hingorani A, Ascher E, Scheinman M, et al.: The effect of tumor necrosis factor binding protein and interleukin-1 receptor antagonist on the development of abdominal aortic aneurysms in a rat model. J Vasc Surg 1998, 28:522–526.
Gargiulo M, Stella A, Spina M, et al.: Content and turnover of extracellular matrix protein in human “nonspecific” and inflammatory abdominal aortic aneurysms. Eur J Vasc Surg 1993, 7:546–553.
McMillan WD, Pearce WH: Increased plasma levels of metalloproteinase-9 are associated with abdominal aortic aneurysms. J Vasc Surg 1999, 29:122–127.
Goodall S, Crowther M, Hemingway DM, et al.: Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms. Circulation 2001, 104:304–309.
Thompson RW, Holmes DR, Mertens RA, et al.: Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms-an elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. J Clin Invest 1995, 96:318–326.
Curci JA, Liao SX, Huffman MD, et al.: Expression and localization of macrophage elastase (Matrix metalloproteinase-12) in abdominal aortic aneurysms. J Clin Invest 1998, 102:1900–1910.
Irizarry E, Newman KM, Gandhi RH, et al.: Demonstration of interstitial collagenase in abdominal aortic aneurysm disease. J Surg Res 1993, 54:571–574.
Newman KM, Ogata Y, Malon AM, et al.: Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm. Arterioscler Thromb 1994, 14:1315–1320.
Mao D, Lee JK, VanVickle SJ, et al.: Expression of collagenase-3 (MMP-13) in human abdominal aortic aneurysms and vascular smooth muscle cells in culture. Biochem Biophys Res Commun 1991, 261:904–910.
Pyo R, Lee JK, Shipley JM, et al.: Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest 2000, 105:1641–1649.
Allaire E, Forough R, Clowes M, et al.: Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model. J Clin Invest 1998, 102:1413–1420.
Bigatel DA, Elmore JR, Carey DJ, et al.: The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms. J Vasc Surg 1999, 29:130–138.
Prescott MF, Sawyer WK, Von Linden-Reed J, et al.: Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice overexpressing MMP-3, MMP-12, and MMP-13 and on restenosis in rats after balloon injury. Ann NY Acad Sci 1999, 878:179–190.
Huffman MD, Curci JA, Moore G, et al.: Functional importance of connective tissue repair during the development of experimental abdominal aortic aneurysms. Surgery 2000, 128:429–438.
Mosorin M, Juvonen J, Biancari F, et al.: Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. J Vasc Surg 2001, 34:606–610.
Reilly JM, Sicard GA, Lucore CL: Abnormal expression of plasminogen activators in aortic aneurysmal and occlusive disease. J Vasc Surg 1994, 19:865–872.
Schneiderman J, Bordin GM, Engelberg I, et al.: Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall—a possible mechanism for aneurysm expansion. J Clin Invest 1995, 96:639–645.
Shireman PK, McCarthy WJ, Pearce WH, et al.: Elevations of tissue-type plasminogen activator and differential expression of urokinase-type plasminogen activator in diseased aorta. J Vasc Surg 1997, 25:157–164.
Allaire E, Hasenstab D, Kenagy RD, et al.: Prevention of aneurysm development and rupture by local overexpression of plasminogen activator inhibitor-1. Circulation 1998, 98:249–255.
Kuhlencordt PJ, Gyurko R, Han F, et al.: Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 2001, 104:448–454.
Chen J, Kuhlencordt PJ, Astern J, et al.: Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein E/endothelial nitric oxide synthase double knockout mice. Circulation 2001, 104:2391–2394.
Lee JK, Borhani M, Ennis TL, et al.: Experimental abdominal aortic aneurysms in mice lacking expression of inducible nitric oxide synthase. Arterioscler Thromb Vasc Biol 2001, 21:1393–1401.
Daugherty A, Cassis L: Chronic angiotensin II infusion promotes atherogenesis in low density lipoprotein receptor -/- mice. Proc NY Acad Sci 1999, 892:108–118.
Daugherty A, Manning MW, Cassis LA: Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest 2000, 105:1605–1612.
Wang YX, Martin McNulty B, Freay AD, et al.: Angiotensin II increases urokinase-type plasminogen activator expression and induces aneurysm in the abdominal aorta of apolipoprotein E-deficient mice. Am J Pathol 2001, 159:1455–1464.
Daugherty A, Manning MW, Cassis LA: Antagonism of AT2 receptors augments Angiotensin II-induced abdominal aortic aneurysms and atherosclerosis. Br J Pharmacol 2001, 134:865–870.
Manning MW, Cassis LA, Huang J, et al.: Abdominal aortic aneurysms: fresh insights from a novel animal model of the disease. Vasc Med 2002, in press.
Liao S, Miralles M, Kelley BJ, et al.: Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors. J Vasc Surg 2001, 33:1057–1064.
Takenaka K, Yamakawa H, Sakai H, et al.: Angiotensin I-converting enzyme gene polymorphism in intracranial saccular aneurysm individuals. Neurol Res 1998, 20:607–611.
Keramatipour M, McConnell RS, Kirkpatrick P, et al.: The ACE I allele is associated with increased risk for ruptured intracranial aneurysms. J Med Genet 2000, 37:498–500.
Pola R, Gaetani E, Santoliquido A, et al.: Abdominal aortic aneurysm in normotensive patients: association with angiotensin-converting enzyme gene polymorphism. Eur J Vasc Endovasc Surg 2001, 21:445–449.
Treska V, Wenham PW, Valenta J, et al.: Plasma endothelin levels in patients with abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 1999, 17:424–428.
Libby P: Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001, 104:365–372.
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Daugherty, A., Cassis, L.A. Mechanisms of abdominal aortic aneurysm formation. Curr Atheroscler Rep 4, 222–227 (2002). https://doi.org/10.1007/s11883-002-0023-5
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DOI: https://doi.org/10.1007/s11883-002-0023-5