title: Serum markers of collagen type I metabolism in spontaneously hypertensive rats: relation to myocardial fibrosis.
abstract: BACKGROUND
  The assay of serum peptides of extracellular collagen synthesis and degradation could provide an indirect estimate of the rate of fibrillar turnover. This study was designed to investigate whether serum peptides of collagen type I synthesis and degradation are altered in spontaneously hypertensive rats (SHR) with left ventricular hypertrophy and whether these serum collagen-derived peptides are related to myocardial fibrosis.
  
  
  RESULTS
  We measured serum levels of carboxyterminal propeptide of procollagen type I (PIP) as a marker of collagen I synthesis and serum levels of the pyridinoline crosslinked telopeptide domain of collagen type I (CITP) as a marker of fibrillar collagen I degradation in ten 36-week-old normotensive Wistar-Kyoto (WKY) rats, ten 36-week-old SHR, and ten 16-week-old SHR treated with the angiotensin-converting enzyme inhibitor quinapril (10 mg /kg body wt per day, orally) for 20 weeks. PIP and CITP were determined by specific radioimmunoassays. Histomorphometric and immunohistochemical studies of the left ventricle were performed in all rats. In untreated SHR compared with WKY rats, we found a more extensive interstitial and perivascular fibrosis, an increased (P<.01) collagen volume fraction, a more marked deposition of collagen type I, an increased (P<.01) serum concentration of PIP, and a similar serum concentration of CITP. In quinapril-treated SHR compared with untreated SHR, we found an absence of left ventricular hypertrophy, a marked decrease of fibrosis, a lower (P<.01) collagen volume fraction, a diminished deposition of collagen type I, a decreased (P<.01) concentration of PIP, and a similar concentration of CITP. A direct correlation was found between the collagen volume fraction and serum PIP (r=.753, P<.05) in untreated SHR.
  
  
  CONCLUSIONS
  These results suggest that tissue metabolism of collagen type I is abnormal in SHR and can be normalized by treatment with quinapril. On the basis of our findings, we propose that serum PIP may be a marker of collagen type I-dependent myocardial fibrosis in rats with genetic hypertension.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Navarra, Pamplona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Díez
authors.forename: A
authors.initials: A
authors.lastname: Panizo
authors.forename: M J
authors.initials: MJ
authors.lastname: Gil
authors.forename: I
authors.initials: I
authors.lastname: Monreal
authors.forename: M
authors.initials: M
authors.lastname: Hernández
authors.forename: J
authors.initials: J
authors.lastname: Pardo Mindán
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D005355:Fibrosis; D006973:Hypertension / Q000097:blood* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications; D007150:Immunohistochemistry; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D003094:Collagen