Molecular diversity in the abdominal aortic aneurysm phenotype

M. D. Tilson and M. P. Roberts
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510.

Abnormalities of collagenous peptides were detected among a group of 20 patients with abdominal aortic aneurysms, studied by high-performance liquid chromatography/NaDodSO4-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis of the cyanogen bromide (CB) cleavage products of insoluble skin protein. Three abnormal patterns were identified as follows: (1) relative deficiency of a peptide with a relative molecular mass of approximately 58 kilodaltons (four patients); (2) relative decrease in the ratio of alpha-2 to alpha-1 (I) CB peptides (seven patients); and (3) decreased detection of all collagenous CB and pepsin cleavage products (one patient, who was also heterozygous for the Z allele of alpha 1-antitrypsin). The "minimal hypothesis" to explain these findings is that most of the observed abnormalities can be explained by collagenolysis in vitro, although a mutation in the primary structure of collagen has not been ruled out in all patients. Molecular heterogeneity appears to occur within the aneurysm phenotype, and the findings in the patient in group 3 allow identification of one possible risk factor in abdominal aortic aneurysmal disease that has a genomic assignment.