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Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficiencies of total collagen, type III collagen, and elastin have been proposed to explain aneurysm formation. Infrarenal aortas were collected from 19 patients (age 70 +/- 7 years) undergoing operative repair of abdominal aortic aneurysms (diameter 7 +/- 2 cm) and from 13 autopsies (age 63 +/- 17 years) of patients without aneurysm disease (controls). Wall thickness and collagen and elastin concentration were determined in full-thickness aorta. Collagen types I and III were measured after digestion with cyanogen bromide, which solubilized nearly 90% of total collagen for typing. Cyanogen bromide peptides were separated by sequential carboxymethylcellulose and agarose chromatography and quantified by peak area measurement with computerized image analysis. Histologic examination revealed prominent inflammatory cell infiltration and deficient, fragmented elastin in the aneurysms. Aortic wall thickness was similar in aneurysms and in control specimens. In the aneurysms, collagen was increased (37% +/- 16% vs 24% +/- 5%; p less than 0.05) and elastin was decreased (1% +/- 1% vs 12% +/- 7%; p less than 0.001), expressed as a percentage of delipidized, decalcified dry weight. Collagen type I accounted for 74% +/- 4% of aneurysm and 73% +/- 4% of control collagen solubilized for typing, and collagen type III accounted for 26% +/- 4% of aneurysm and 27% +/- 4% of control collagen solubilized for typing. Neither patients with a family history of aneurysms nor those without a history of aneurysms had collagen type III deficiency. Atherosclerotic abdominal aortic aneurysms are associated with an inflammatory process and may result from elastin degradation and not a deficiency of type III collagen.