Early degradation and serum appearance of type I collagen fragments after myocardial infarction.
Although extracellular matrix-degrading enzymes matrix metalloproteinases (MMPs) are activated within minutes after myocardial infarction (MI), the time course of early MI-induced type I cardiac collagen degradation has not been assessed, nor has the ability of MMP inhibitor compounds, such as doxycycline (DOX), to limit these events. The objective of this study was to assess serum biomarker evidence of myocardial type I collagen degradation early (<48 h) after coronary occlusion (CO) and determine the capacity of DOX to ameliorate its release. CO studies were performed in untreated and DOX pre-treated pigs. Treated animals received DOX at 30 mg/kg/d. Radioimmunoassays were performed for serum levels of C-terminal telopeptide of collagen type I (ICTP) fragments. ICTP groups peaked by 6 h after MI. However, in DOX-treated animals, ICTP values returned to normal by 8 h. Average serum concentrations for ICTP values from 0 to 48 h post-MI were significantly inhibited by DOX treatment. In conclusion, serum biomarker results indicate that type I collagen degradation occurs within minutes after MI and that DOX likely reduces its degradation.
Villarreal
Francisco
F
Department of Medicine, University of California, San Diego, CA, USA. fvillarr@ucsd.edu
Omens
Jeffrey
J
Dillmann
Wolfgang
W
Risteli
Juha
J
Nguyen
Judy
J
Covell
James
J
D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry*; D004318:Doxycycline / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000097:blood*; D009206:Myocardium / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D011863:Radioimmunoassay; D013552:Swine; D013997:Time Factors; D020257:Ventricular Remodeling
D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D002248:Carbon Monoxide; D003094:Collagen; D004318:Doxycycline