title: Type I collagen degradation during tissue repair: comparison of mechanisms following fracture and acute coronary syndromes.
abstract: There is turnover of type I collagen during tissue repair. The degradation of type I collagen by matrix metalloproteinases (MMPs) is reflected by serum ICTP and that by cathepsins by CTX-I. There is evidence for increases in ICTP after acute coronary syndromes (ACS) and in CTX-I during fracture repair. The involvement of the MMP pathway in fracture repair and cathepsins after myocardial infarction is unclear. We studied 74 men; 22 were admitted to the hospital on the day of their ACS (ST or non-ST elevation myocardial infarction) (mean age 56 years, range 39 to 82) and 9 attended hospital on the day of their tibial shaft fracture (mean age 33 years, range 21 to 79); we had 43 age-matched controls (mean age 54 years, range 20 to 82). Subjects with ACS and tibial shaft fracture were followed up for up to one year; control subjects were used to establish a reference interval. We measured serum ICTP by ELISA (reference interval 1.1 to 17.6 ng/mL) and CTX-I by chemiluminescence (reference interval 0.094 to 0.991 ng/mL). After ACS, the mean ICTP increased from 5.41 to 6.60 ng/mL within one day of admission (p<0.05); the mean CTX-I increased from 0.263 to 0.414 ng/mL (p<0.05). In two cases, the CTX increased to above the reference interval. After tibial shaft fracture, the mean ICTP increased from 5.51 to maximum of 8.71 ng/mL within 28 days of admission (p<0.01); the mean CTX increased from 0.200 to 0.374 ng/mL (p<0.001). In four cases, the CTX increased to above the reference interval. We conclude that the MMP and cathepsin pathways are both implicated in tissue repair in the bone and heart. This may have clinical implications; drugs that block either pathway (TIMPs, cathepsin K inhibitors) may affect the repair of both tissues.
authors.affiliation: Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Stansfield
authors.affiliation: Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Fatma
authors.initials: F
authors.lastname: Gossiel
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom; Department of Cardiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
authors.forename: Allison
authors.initials: A
authors.lastname: Morton
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Newman
authors.affiliation: Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom. Electronic address: r.eastell@sheffield.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
mesh_terms: D054058:Acute Coronary Syndrome / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D013978:Tibial Fractures / Q000378:metabolism*; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide
keywords: Acute coronary syndromes; Collagen turnover markers