Deficient prolylcarboxypeptidase gene and protein expression in left ventricles of spontaneously hypertensive rats (SHR) |
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| Affiliation: | 1. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil;2. Department of Physiology, Medical School of São Paulo, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil;1. Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland;2. Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland;1. School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, MC, Italy;2. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, 37135 Verona, Italy;3. School of Biosciences and Biotechnology, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy;3. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461;4. Department of Biology, CUNY College of Staten Island, New York, New York 10314;5. Touchstone Diabetes Center, Department of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390;1. Department of Statistics, National Cheng Kung University, Tainan 70101, Taiwan, ROC;2. Department of Applied Mathematics, National Chiayi University, Chiayi 60004, Taiwan, ROC |
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| 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. |
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| Keywords: | Heart 2K-1C Kallikrein–kinin system Prolylcarboxypeptidase Renin–angiotensin system SHR |
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