Cellular, enzymatic, and genetic factors in the pathogenesis of abdominal aortic aneurysms.
Aneurysms of the abdominal aorta occur with atherosclerosis or connective tissue disorders. Changes of three components of aortic media, smooth muscle cells, elastin, and collagen, which could contribute to medial weakening, are discussed. Smooth muscle cells cultured from the aging abdominal aorta (normal, atherosclerotic, or aneurysmal) have limited replicative potential at five to six cell doublings, whereas cells from aneurysmal thoracic aorta undergo more than 20 cell doublings in culture. The elastin content is much reduced in aneurysms and this is associated with an increase in elastase activity of medial homogenates to 17.8 U/ng of deoxyribonucleic acid (DNA) compared with 8.3 and 4.4 U/ng of DNA in atherosclerotic and normal aorta, respectively. An elastinolytic enzyme has been purified from aneurysmal aorta and appears to have different properties from human leukocyte elastase. Ruptured aneurysms are associated with an increased total collagenase activity but the increase could be stimulated by, or result from, an influx of inflammatory cells and does not necessarily have a causal significance. In patients with a family history of aneurysm there appears to be a decreased content of type III collagen in aortic media: 24% +/- 4% compared with 32% +/- 5% in most aneurysms. Familial aneurysms are most common in women, and preliminary results suggest that a polymorphic variant of the type III collagen gene, defined by restriction enzyme digest, may be associated with aneurysmal disease in women. The genetic approach may define causal mechanisms predisposing patients to aneurysmal dilatation.
Powell
J
J
Department of Surgery, Charing Cross & Westminster Medical School, London, England.
Greenhalgh
R M
RM
D000368:Aged; D001012:Aorta, Abdominal / Q000032:analysis / Q000201:enzymology / Q000473:pathology; D001014:Aortic Aneurysm / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D003094:Collagen / Q000032:analysis / Q000235:genetics; D004247:DNA / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000032:analysis; D003012:Microbial Collagenase / Q000032:analysis; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010196:Pancreatic Elastase / Q000032:analysis; D010641:Phenotype
D008055:Lipids; D003094:Collagen; D004247:DNA; D004549:Elastin; D010196:Pancreatic Elastase; D003012:Microbial Collagenase