Quantitative measurement of mature collagen cross-links in human carotid artery plaques.
While there is an appreciable understanding of the importance of collagen breakdown in contributing to atherosclerotic plaque vulnerability and rupture, little is known about changes in collagen maturation in the atherosclerotic plaque. This is achieved through the formation of the covalent intermolecular cross-links pyridinoline (Pyd) and deoxypyridinoline (Dpd). In this study we collected carotid endarterectomy specimens from patients and undertook (i) histological assessment of collagen and inflammatory cell distribution and (ii) biochemical analysis of total collagen and cross-link content. Greater collagen deposition, increased presence of CD68 positive cells and an increased Pyd:Dpd ratio (an indicator of lysyl hydroxylase (LH-1) activity) were found in plaque versus normal vascular tissue. These findings are the first measurements of Pyd and Dpd cross-links in normal and atherosclerotic vascular tissue. The observed differences in cross-links in the plaque may adversely affect tensile strength and may have relevance to the mechanisms underlying rupture of vulnerable plaques.
Hector
Emma E
EE
School of Pharmacy & Life Sciences, Institute for Health & Welfare Research, The Robert Gordon University, Schoolhill, Aberdeen AB10 1FR, Scotland, UK.
Robins
Simon P
SP
Mercer
Derry K
DK
Brittenden
Julie
J
Wainwright
Cherry L
CL
D000368:Aged; D000596:Amino Acids / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D050197:Atherosclerosis / Q000473:pathology; D002309:Cardiology / Q000379:methods; D016893:Carotid Stenosis / Q000175:diagnosis* / Q000473:pathology; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D016894:Endarterectomy, Carotid / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000096:biosynthesis; D000097382:CD68 Molecule
D000596:Amino Acids; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003094:Collagen; D003432:Cross-Linking Reagents; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C015484:pyridinoline; C036020:deoxypyridinoline