title: Deficient prolylcarboxypeptidase gene and protein expression in left ventricles of spontaneously hypertensive rats (SHR).
abstract: Prolylcarboxypeptidase (PRCP), an endothelial cell membrane serine peptidase that inactivates angiotensin II and activates pre-kallikrein, is thought to have anti-hypertensive and anti-proliferative roles in cardiovascular homeostasis. We hypothesized that PRCP function may be altered in heart tissue under conditions that predispose to left ventricle hypertrophy (LVH) in rats. We therefore used real-time PCR and western-blotting to examine the mRNA and protein expression of PRCP in the hearts of spontaneously hypertensive rats (SHR) at pre-hypertensive (5-week-old) and hypertensive (16-week-old) stages compared with age-matched hypertensive (2 kidney-1 clip; 2K-1C) rats and normotensive Wistar rats. PRCP mRNA expression was significantly reduced in hearts of 5- and 16-week-old SHR compared with age-matched Wistar controls, 2K-1C hypertensive rats and sham-operated normotensive rats. There were no significant differences in the PRCP mRNA and protein expression levels in hearts from hypertensive renovascular and sham-operated normotensive rats. Prolonged treatment of SHR with the AT1 receptor antagonist losartan (40 mg/kg, gavage for 8 weeks) reduced the left ventricular weight/body weight ratio (LVW/BW), as well as the mRNA expression of collagen type 1, collagen type 3 and MMP9 in left ventricular tissue, without affecting PRCP gene and protein expression. Our results suggest that diminished PRCP gene and protein expression might be constitutionally involved in the SHR phenotype. In addition, since neither the development of arterial hypertension in the 2K-1C model nor its successful treatment in SHR altered PRCP gene and protein expression in heart tissue, it appears unlikely that PRCP function is regulated by the renin-angiotensin system or by afterload conditions.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil. Electronic address: rossanamarangoni@yahoo.com.
authors.forename: Rossana Anderson
authors.initials: RA
authors.lastname: Marangoni
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Rosangela Aparecida
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Department of Physiology, Medical School of São Paulo, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Piccolo
mesh_terms: D000818:Animals; D002268:Carboxypeptidases / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D006352:Heart Ventricles / Q000201:enzymology* / Q000473:pathology; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System
chemical_list: D012333:RNA, Messenger; D002268:Carboxypeptidases; C022448:lysosomal Pro-X carboxypeptidase
keywords: 2K-1C; Heart; Kallikrein–kinin system; Prolylcarboxypeptidase; Renin–angiotensin system; SHR