Collagen cross-link synthesis in cultured vascular endothelium.
Cultured vascular endothelium secretes the enzyme lysyl oxidase which cross-links both collagen and elastin. The major reducible cross-link synthesized by cultured human umbilical arterial and venous endothelium is dihydroxylysinonorleucine (di-OH-LNL). Treatment of the cultures with the lathyrogen beta-aminopropionitrile (BAPN), which inhibits lysyl oxidase, inhibited synthesis of this cross-link. Cultured porcine aortic endothelium synthesized three major reducible lysine-derived cross-links: dihydroxylysinonorleucine (di-OH-LNL), hydroxylysinonorleucine (OH-LNL) and lysinonorleucine (LNL); BAPN also inhibited synthesis of these three cross-links. Earlier in-vivo observations on BAPN-treated chick embryos had shown a 20% increase in the hydration of cartilage and other tissues; the likeliest explanation was that cross-link disruption permitted the proteoglycans in cartilage to express their hydrophilic nature when freed of their collagenous network. Capillary basement membrane contains laminin, proteoglycan and type IV collagen. Following the finding of oedema in lathyritic cartilage, we would propose that agents which disrupt collagen cross-links in cultured vascular endothelium, damaging capillary basement membrane, be considered as one possible mechanism in the pathogenesis of oedema.
Levene
C I
CI
Department of Pathology, University of Cambridge, UK.
Heale
G
G
Robins
S P
SP
D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D046508:Culture Techniques; D004151:Dipeptides / Q000096:biosynthesis*; D004487:Edema / Q000209:etiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D013552:Swine; D014469:Umbilical Arteries / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism
D004151:Dipeptides; C007428:5,5'-dihydroxylysylnorleucine; D000629:Aminopropionitrile; C010991:delta-hydroxylysylnorleucine; C002961:lysinenorleucine; D003094:Collagen