(Circulation. 1996;93:1026-1032.)
© 1996 American Heart Association, Inc.
Articles |
Serum Markers of Collagen Type I Metabolism in Spontaneously Hypertensive Rats
Relation to Myocardial Fibrosis
From the Vascular Pathophysiology Unit, Department of Internal Medicine, School of Medicine, University of Navarra and Department of Medicine, School of Medicine, University of Zaragoza (J.D., M.H.); the Department of Pathology, University Clinic, University of Navarra (A.P., J.P.M.); and the Department of Clinical Chemistry, University Clinic, University of Navarra, Pamplona, Spain (M.J.G., I.M.).
Correspondence to Javier Díez, MD, PhD, Unidad de Fisiopatología Vascular Departamento de Medicina Interna, Facultad de Medicina, C/ Irunlarrea s/n, 31080 Pamplona, Spain.
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.
Methods and Results We measured serum levels of carboxy-terminal propeptide of procollagen type I (PIP) as a marker of collagen I synthesis and serum levels of the pyridinoline cross-linked 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.
Key Words: collagen • hypertension • peptides • fibrosis
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