desmosine and Aortic-Diseases

Elastin calcification is a widespread feature of vascular pathology, and circumstantial evidence exists for a correlation between elastin degradation and calcification. We hypothesized that matrix metalloproteinase (MMP)-mediated vascular remodeling plays a significant role in elastin calcification.. In the present studies, we determined that short-term periadventitial treatment of the rat abdominal aorta with low concentrations of calcium chloride (CaCl2) induced chronic degeneration and calcification of vascular elastic fibers in the absence of aneurysm formation and inflammatory reactions. Furthermore, the rate of progression of calcification depended on the application method and concentration of CaCl2 applied periarterially. Initial calcium deposits, associated mainly with elastic fibers, were persistently accompanied by elastin degradation, disorganization of aortic extracellular matrix, and moderate levels of vascular cell apoptosis. Application of aluminum ions (known inhibitors of elastin degradation) before the CaCl2-mediated injury significantly reduced elastin calcification and abolished both extracellular matrix degradation and apoptosis. We also found that MMP-knockout mice were resistant to CaCl2-mediated aortic injury and did not develop elastin degeneration and calcification.. Collectively, these data strongly indicate a correlation between MMP-mediated elastin degradation and vascular calcification.

Topics: Animals; Aorta, Abdominal; Aortic Diseases; Calcinosis; Calcium; Calcium Chloride; Capillary Permeability; Desmosine; Elastic Tissue; Elastin; Endothelium, Vascular; Extracellular Matrix; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Rats; Rats, Sprague-Dawley; Tunica Media

To examine the qualitative changes of elastin and the aorta related to calcification of human arteries, biochemical properties were measured, including calcium (Ca), phosphorus (P) and magnesium (Mg) contents in the aorta or in the elastin fraction in calcification, cholesterol content in atherosclerosis, desmosine content of cross-link, free thiol contents (free SH/total SH) and hydrophobic properties in the elastin fraction from the calcified portion, adjacent sites and another normal artery. The results from different sites of the calcified abdominal artery are as follows: The contents of Ca, P and Mg in aorta and the elastin fraction from the calcification site were higher than those at other sites. Moreover, Ca in the aorta and elastin fraction correlated positively with P and Mg. The content of cholesterol in the calcification site was the same as at other sites and did not correlate with Ca, P or Mg. The content of desmosine in the calcification site was significantly lower than that in different sites. In addition, its content was negatively associated with Ca and P in the elastin fraction and with the aortic Mg. The content of free thiol in the calcification site was similar to the other sites and correlated negatively with Ca and P in the aorta. The hydrophobicity in the calcification was similar to that at other sites, and was negatively associated with Ca and Mg in the elastin fraction.

Topics: Aged; Aged, 80 and over; Aorta; Aorta, Abdominal; Aortic Diseases; Calcinosis; Calcium; Cholesterol; Desmosine; Elastin; Humans; Magnesium; Middle Aged; Phosphorus; Sulfhydryl Compounds

The activity of lysyl oxidase, the cross-linking enzyme of elastin and collagen, was measured in culture media of human skin fibroblasts, human aortic medial smooth muscle cells (SMCs) and adventitial fibroblasts using [3H]lysine-labelled elastin substrate. In addition, biosynthesis of isodesmosine and desmosine, the cross-linking amino acids of elastin, was studied by metabolic labelling with [14C]lysine and subsequent amino acid chromatography of protein hydrolysates. Lysyl oxidase activity in culture media of skin fibroblasts and aortic smooth muscle cells increased with the growth of the cell population and was at the highest level in cultures of high cell density. Lysyl oxidase activity in the aortic cell cultures was about three times that of skin fibroblasts. Aortic smooth muscle cells synthesized at least 100 times more desmosines than skin or adventitial fibroblasts. No differences were observed in lysyl oxidase activity and synthesis of desmosines between aortic smooth muscle cells or skin fibroblasts from patients with the Marfan syndrome or other annulo-aortic ectasia (dilatation of the ascending aorta) and the corresponding controls.

Topics: Adolescent; Adult; Amino Acid Oxidoreductases; Amino Acids; Aorta; Aortic Diseases; Aortic Valve Insufficiency; Cell Line; Cells, Cultured; Child; Desmosine; Dilatation, Pathologic; Female; Fibroblasts; Humans; Male; Marfan Syndrome; Middle Aged; Protein-Lysine 6-Oxidase; Skin

Elastin and collagen concentrations were determined in intimal-medial samples of ascending aortas from healthy controls of different ages and from 20 patients with annuloaortic ectasia (AAE). Five patients had the Marfan syndrome. In controls the highest elastin concentrations (estimated from desmosine concentrations or insoluble residues after hot-alkali extraction) were found in children. During aging until 60 years, elastin concentration decreased when determined by the hot-alkali extraction method while desmosine concentration changed less. Aorta samples from the Marfan-syndrome patients showed a great variation of elastin concentration from total lack to normal values. Samples from the other AAE patients could be divided into two groups. One contained clearly less elastin and more collagen than the controls whereas in the other group this difference was less marked. Histological examination of the aortic wall of the first group also showed marked fibrosis accompanied by severe elastin fragmentation and acellularity. From the 15 non-Marfan patients 14 were men. By means of clinical examination these patients could also be divided into "familial" and "nonfamilial" groups, because increased diameter of the aortic root was found in relatives of almost half of the patients. However, there were no differences in elastin and collagen concentrations between the familial and nonfamilial cases. As well, no correlation was found between biochemical findings and diameters of the aortic roots. These results point to altered elastin and/or collagen metabolism in the aortic wall of AAE patients.

Topics: Adolescent; Adult; Aged; Amino Acids; Aorta; Aortic Diseases; Child; Collagen; Desmosine; Elastin; Female; Humans; Male; Marfan Syndrome; Middle Aged

Lesions of the aorta and other organs of copper depleted layers, roosters, day-old chicks and chick embryos were studied by light- and electron microscopy. Copper deficiency results in late and abnormal development of elastic fibres: inhibition of the formation of cross linkages causes a decline of elastin synthesis. The microfibrils constituting the blackbone of the elastic fibre form a honey-comb pattern. The small amount of amorphous elastin is digestible by elastase, the microfibrils are resistant to the action of the enzyme. The aortic elastic fibres are irregularly shaped, broken revealing a honey-comb like pattern. They maintain an increased affinity to PTA. Tears--dissecting aneurysms--arise in the media, vacuoles appear in the heart muscle, haemorrhages and inflammatory changes may arise in other organs.

Topics: Animals; Aorta; Aortic Diseases; Chick Embryo; Chickens; Copper; Desmosine; Elastic Tissue