Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta

Abstract

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 tetrapetide, 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 < 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. While elastin is depleted in abdominal aortic aneurysm tissue, this could not be attributed to a deficiency of stable cross-links. Elastin mRNA is present in abdominal aortic aneurysm and no aneurysmal disease tissues. The decreased elastin concentration and altered amino acid composition of the abdominal aortic aneurysm NaOH insoluble residue suggests a marked increase of microfibrillar protein in this fraction.