Aortic aneurysm formation: lessons from human studies and experimental models.

The development of a saccular (nondissecting) aortic aneurysm follows the destruction of the connective tissue in the media, in particular the elastic lamellae. The vessel wall is then unable to withstand the expansile force of each systolic contraction. The current view is that the great majority of aortic aneurysms, >90% of which are below the renal arteries, are associated with atherosclerosis.1 This view is based on the fact that the lower abdominal aorta is the site at which atherosclerosis first develops and confluent intimal involvement becomes common by middle age. Resected abdominal aortic aneurysms show advanced atherosclerosis with mural thrombus in the wall. This view, however, is a paradox in that atherosclerosis is an intimal disease, whereas in the abdominal aorta, aneurysms are due to major medial damage. There are also other reasons to believe that aortic aneurysms have an additional component to their pathogenesis. Abdominal aortic aneurysms are familial and under genetic influences unrelated to lipid-related risk factors for atherosclerosis. First-degree relatives of index cases with abdominal aortic aneurysms have a significantly higher risk of developing a similar lesion when compared with the general population. Prospective family studies suggest a figure of 14.5% for offspring and 13% to 32% for siblings compared with the general population risk of 2% to 5%.2 3 4 Risk factors such as elevated plasma cholesterol, hypertriglyceridemia, hypertension, and smoking are found in many subjects with abdominal aortic aneurysms, yet 60% of cases have plasma cholesterol levels of <240 mg/dL.1 Smoking is the single largest external contributor to the risk of aortic aneurysm formation. These data suggest that there are additional factors involved in aortic aneurysm formation.5 Some of the factors are genetic. A very small subgroup of saccular aneurysms are due to genes controlling connective tissue structural proteins. The fibrillin …

[1]  J. Powell,et al.  Multifactorial inheritance of abdominal aortic aneurysm. , 1987, European journal of vascular surgery.

[2]  H. Nagase,et al.  Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[3]  J. Powell,et al.  Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[4]  R. Mecham,et al.  Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. , 1995, The Journal of clinical investigation.

[5]  F. Schoen,et al.  Cardiovascular Pathology: Clinicopathologic Correlations and Pathogenetic Mechanisms , 1995 .

[6]  G. Tromp,et al.  Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms. , 1993, The Journal of clinical investigation.

[7]  Jon R. Cohen,et al.  α1-Antitrypsin phenotypes in patients with abdominal aortic aneurysms , 1990 .

[8]  R. Busuttil,et al.  Collagenase activity of the human aorta. A comparison of patients with and without abdominal aortic aneurysms. , 1980, Archives of surgery.

[9]  É. Allaire,et al.  Prevention of aneurysm development and rupture by local overexpression of plasminogen activator inhibitor-1. , 1998, Circulation.

[10]  A. Sadovnick,et al.  Sibling risks of abdominal aortic aneurysm , 1995, The Lancet.

[11]  J. Powell,et al.  Pathogenesis of abdominal aortic aneurysm , 1994, The British journal of surgery.

[12]  J. McEwan,et al.  Matrix metalloproteinases and cardiovascular disease. , 1995, Circulation research.

[13]  H. Dietz.  New insights into the genetic basis of aortic aneurysms. , 1995, Monographs in pathology.

[14]  N. Poulter,et al.  Abdominal aortic aneurysm: REPORT OF A MEETING OF PHYSICIANS AND SCIENTISTS, UNIVERSITY COLLEGE LONDON MEDICAL SCHOOL , 1993 .

[15]  G. Hunter.  Are aortic aneurysms caused by atherosclerosis?: Reed D, Reed C, Stemmermann G, Hayashi T. Circulation 1992; 85: 205–211 , 1993 .

[16]  K. Bland,et al.  Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. , 1990, The Journal of surgical research.

[17]  P. Libby.  Molecular bases of the acute coronary syndromes. , 1995, Circulation.

[18]  W. Marks,et al.  Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report. , 1991, The Journal of surgical research.

[19]  W. Pearce,et al.  In situ localization and quantification of mRNA for 92-kD type IV collagenase and its inhibitor in aneurysmal, occlusive, and normal aorta. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[20]  R. Read,et al.  Blood elastolytic activity in patients with aortic aneurysm. , 1982, The Annals of thoracic surgery.

[21]  J. Powell,et al.  Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm. , 1990, Clinical science.

[22]  M. Lever,et al.  Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysm in rabbits. , 1997, Arteriosclerosis, thrombosis, and vascular biology.