Atherosclerosis 152 (2000) 531 – 532
Letter to the Editors
www.elsevier.com/locate/atherosclerosis
Atherosclerosis, type I collagen cross-linking and homocysteine
Patients with homocystinuria have several connec-tive tissue manifestations, the most severe being atherosclerosis. Furthermore, elevated plasma homo-cysteine concentrations correlate with atherosclerosis without other features of homocystinuria [1]. Homo-cysteine has been shown to interfere with collagen cross-linking, although the exact biochemical mecha-nism is unclear [2]. Moreover, the serum level of car-boxyterminal telopeptide of human type I collagen (ICTP), the degradation product of type I collagen, decreases in patients with homocystinuria [3]. Thus, the decreased tensile strength of the connective tissue may be at least partially responsible for the clinical manifestations of homocystinuria. We have recently shown that the ICTP assay detects only degradation of mature, trivalently cross-linked type I collagen [4]. We, therefore, wanted to study if there really is a negative correlation between serum homocysteine and ICTP concentrations in patients with severe coronary
atherosclerosis.
Serum samples were obtained from 109 consecutive patients (75 men, 34 women, mean age 6299) before coronary artery bypass grafting at the Oulu Univer-sity Hospital. Forty-nine of the patients had previ-ously suffered a myocardial infarction and 70 patients had three-vessel disease. The collection of the samples was approved by the local ethics committee. Homo-cysteine (reference range 4.5 – 12.4 mmol/l) and ICTP
(reference range 1.6 – 4.6 mmol/l) were measured by
commercially available methods (Abbott Laboratories and Orion Diagnostica, respectively). Spearman’s rank correlation was used for the correlation analyses.
The mean ICTP and homocysteine concentrations were 3.391.3 and 14.494.8 mg/l, respectively. These
correlated significantly with each other (r=0.260, P=0.006) (Fig. 1). However, both ICTP and homo-cysteine also correlated significantly with the age of the patients (r=0.265, P=0.005 and 0.310, P=
0.001, respectively).
We did not find the expected negative correlation between serum ICTP and homocysteine concentra-tions, which suggests that cross-linking of type I col-lagen does not decrease in the presence of increasing homocysteine concentrations, although the observed homocysteine levels were not very high in the present series. Both ICTP and homocysteine correlated signifi-cantly with age. Atherosclerosis, in addition to aging, possibly accelerates the turnover of type I collagen, which may mask the effect of homocysteine on colla-gen cross-linking. Type I collacolla-gen is the major con-stituent of mineralised bone, and thus part of the circulating ICTP could be derived from bone turnover via the matrix metalloproteinase (MMP) pathway [4]. Measurements of type III collagen metabolism with respect to, for instance, plaque rupture might be more relevant, since type III collagen is very abundant in atherosclerotic plaques and vessel walls [5], being ab-sent in bone.
References
[1] Selhub J, Jacques PF, Bostom AG, D’Agostino RB, Wilson PW, Belanger AJ, O’Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Fig. 1. Correlation between serum concentrations of homocysteine
and ICTP in patients with coronary atherosclerosis (n=109).
Abbre6iations: ICTP, cross-linked carboxyterminal telopeptide of type 1 collagen.
Letter to the Editors 532
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[2] Jackson SH. The reaction of homocysteine with aldehyde: an explanation of the collagen defects in homocystinuria. Clin Chim Acta 1973;45:215 – 7.
[3] Lubec B, Fang-Kircher S, Lubec T, Blom HJ, Boers GHJ. Evidence for McKusick’s hypothesis of deficient collagen cross-linking in patients with homocystinuria. Biochim Biophys Acta 1996;1315:159 – 62.
[4] Sassi M-L, Eriksen H, Risteli L, Niemi S, Mansell J, Gowen M, Risteli J. Immunochemical characterization of the assay for the carboxyterminal telopeptide of human type 1 collagen (ICTP). Loss of antigenicity by treatment with cathepsin K. Bone 2000;26:367 – 73.
[5] Bode MK, Mosorin M, Satta J, Risteli L, Juvonen T, Risteli J. Complete processing of type III collagen in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 1999;19:1506 – 11.
Michaela K. Bode Pa¨ivi Laitinen Juha Risteli Department of Clinical Chemistry Uni6ersity of Oulu P.O.Box 5000
FIN-90014 Oulu
Finland E-mail: juha.risteli@oulu.fi
Paavo Uusimaa Department of Internal Medicine Uni6ersity of Oulu P.O.Box 5000
FIN-90014 Oulu
Finland
Tatu Juvonen Department of Surgery Uni6ersity of Oulu P.O.Box 5000
FIN-90014 Oulu
Finland
