desmosine and Calcinosis

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.

Topics: Adult; Aged; Biomarkers; Body Composition; Bronchodilator Agents; Calcinosis; Cardiovascular Diseases; Case-Control Studies; Coronary Vessels; Desmosine; Disease Progression; Elastin; Emphysema; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Pulse Wave Analysis; Respiratory Function Tests; Risk Factors; Smoking; Vascular Stiffness

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

We tested the hypothesis that a simple change in wall composition (medial calcium overload of elastic fibers) can decrease aortic elasticity. Calcium overload was produced by hypervitaminosis D plus nicotine (VDN) in the young rat. Two months later, measurement of central aortic mean blood pressure in the unanesthetized, unrestrained rat showed that the VDN rat suffered from isolated systolic hypertension but that mean blood pressure was normal. Wall thickness and internal diameter determined after in situ pressurized fixation were unchanged, as was calculated wall stress. Wall stiffness was estimated from (1) elastic modulus (determined with the Moens-Korteweg equation and values for aortic pulse wave velocity in the unanesthetized, unrestrained rat and arterial dimensions) and (2) isobaric elasticity (= slope relating pulse wave velocity to mean intraluminal pressure in the phenylephrine-infused, pithed rat preparation). Both increased after VDN, and both were significantly correlated to the wall content of calcium and the elastin-specific amino acids desmosine and isodesmosine. Left ventricular hypertrophy occurred in the VDN model, and left ventricular mass was related to isobaric elasticity. In conclusion, elastocalcinosis induces destruction of elastic fibers, which leads to arterial stiffness, and the latter may be involved in the development of left ventricular hypertrophy in a normotensive model.

Topics: Analysis of Variance; Animals; Aorta; Blood Pressure; Calcinosis; Calcium; Desmosine; Elastic Tissue; Elasticity; Electrophoresis; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Isodesmosine; Linear Models; Male; Nicotine; Rats; Spectrophotometry, Atomic; Tunica Media; Vitamin D

The cross-links histidinoalanine (HA); pyridinoline (Pyr); desmosine (Des); and isodesmosine (Ides) in human atherosclerotic aortas were studied. Only HA showed a significant increase in calcified aortas, with a high concentration in the insoluble "mineralized" fraction, which was separated out after treatment of tissues with pronase E. The cross-links composition was similar among "mineralized" fractions prepared from tissues of varying degrees of calcification: values were 2.40; 0.10; 0.17; and 0.16 moles per 1000 moles of amino acid residues for HA; Pyr; Des; and Ides, respectively. The findings suggest that the HA-containing peptide may play an important role in the calcification process of aortic tissues.

Topics: Amino Acids; Aorta; Arteriosclerosis; Calcinosis; Cross-Linking Reagents; Desmosine; Dipeptides; Humans; Isodesmosine