hydroxylysine and Aortic-Diseases

The collagens are the major structural glycoproteins of connective tissues. A unique primary structure and a multiplicity of post-translational modification reactions are required for normal fibrillogenesis. The post-translational modifications include hydroxylation of prolyl and lysyl residues, glycosylation, folding of the molecule into triple-helical conformation, proteolytic conversion of precursor procollagen to collagen, and oxidative deamination of certain lysyl and hydroxylysyl residues. Any defect in the normal mechanisms responsible for the synthesis and secretion of collagen molecules or the deposition of these molecules into extracellular fibers could result in abnormal fibrillogenesis; such defects could result in a connective tissue disease. Recently, defects in the regulation of the types of collagen synthesized and in the enzymes involved in the post-translational modifications have been found in heritable diseases of connective tissue. Thus far, the primary heritable disorders of collagen metabolism in man include lysyl hydroxylase deficiency in Ehlers-Danlos syndrome type VI, p-collagen peptidase deficency in Ehlers-Danlos syndrome type VII, decreased synthesis of type III collagen in Ehlers-Danlos syndrome type IV, lysyl oxidase deficency in S-linked cutis laxa and Ehlers-Danlos syndrome type V, and decreased synthesis of type I collagen in osteogenesis imperfecta.

Topics: Aortic Diseases; Bone and Bones; Brain Diseases; Collagen; Connective Tissue; Cutis Laxa; Ehlers-Danlos Syndrome; Fascia; Genetic Linkage; Homocystinuria; Humans; Hydroxylysine; Hydroxyproline; Joints; Marfan Syndrome; Microbial Collagenase; Osteogenesis Imperfecta; Protein Biosynthesis; Protein Conformation; Protein-Lysine 6-Oxidase; Sex Chromosomes; Skin Abnormalities

A method is presented for grinding and extracting very small samples of tough fibrous tissue from single atherosclerotic lesions of human aortas. Grinding to a powder was easily accomplished while the samples were frozen in liquid nitrogen in a porcelain micromortar. Extractions of the powder were made first in the mortar and then in tapered centrifuge tubes. Salt soluble, dodecyl sulfate--mercaptoethanol--urea soluble and hot alkali soluble fractions were obtained, in addition to a hot alkali insoluble elastin residue from each sample. Variation in the protein composition of 23 samples from the lumenal surface of the severely atherosclerotic aorta of a 58-year-old human male were determined. The proteins soluble in the buffered-saline and the dodecyl sulfate-urea soluble polypeptides from each sample were analyzed by dodecyl sulfate--acrylamide gel electrophoresis. The amino acid compositions of the insoluble elastin fractions were determined. The 5 grossly normal intima samples had very similar gel electrophoresis band patterns and amino acid compositions. The 3 samples of necrotic gruel had markedly different dodecyl sulfate--urea soluble polypeptides than either normal or calcified tissue; they also had elastin fractions whose amino acid compositions were unique in that they contained 10 times more serine than elastin fractions from grossly normal intima. The 3 calcified samples had less saline or dodecyl sulfate soluble protein than either grossly normal or necrotic gruel samples, and had very altered elastin fraction compositions characterized by much higher contents of hydroxylysine than grossly normal intima. The elastin fractions of necrotic gruel and calcified tissue samples had little or no isodesmosine or desmosine, suggesting that little of the elastin found in healthy aorta tissue was present.

Topics: Amino Acids; Aorta; Aortic Diseases; Arteriosclerosis; Elastin; Humans; Hydroxylysine; Male; Middle Aged; Peptides; Proteins