原创力文档(pro)renin receptor triggers distinct angiotensin ii-independent extracellular matrix remodeling and deterioration of cardiac function(pro)肾素受体触发不同的血管紧张素ii-independent细胞外基质重塑和心脏功能恶化.pdfVIP
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(pro)renin receptor triggers distinct angiotensin ii-independent extracellular matrix remodeling and deterioration of cardiac function(pro)肾素受体触发不同的血管紧张素ii-independent细胞外基质重塑和心脏功能恶化
(Pro)renin Receptor Triggers Distinct Angiotensin II-
Independent Extracellular Matrix Remodeling and
Deterioration of Cardiac Function
1 ¨ 1 1 1 ´ ` 1 1
Anne-Mari Moilanen , Jaana Rysa , Raisa Serpi , Erja Mustonen , Zoltan Szabo , Jani Aro ,
¨ ¨ 2 1 3 3,4 1
Juha Napankangas , Olli Tenhunen , Meeri Sutinen , Tuula Salo , Heikki Ruskoaho *
1 Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland, 2 Department of Pathology, The Institute of Diagnostics,
University of Oulu, Oulu, Finland, 3 Department of Diagnostics and Oral Medicine, Institute of Dentistry, Oulu University Hospital University of Oulu, Oulu, Finland,
4 Institute of Dentistry, University of Helsinki, Finland
Abstract
Background: Activation of the renin-angiotensin-system (RAS) plays a key pathophysiological role in heart failure in patients
with hypertension and myocardial infarction. However, the function of (pro)renin receptor ((P)RR) is not yet solved. We
determined here the direct functional and structural effects of (P)RR in the heart.
Methodology/Principal Findings: (P)RR was overexpressed by using adenovirus-mediated gene delivery in normal adult rat
hearts up to 2 weeks. (P)RR gene delivery into the anterior wall of the left ventricle decreased ejection fraction (P,0.01),
fractional shortening (P,0.01), and intraventricular septum diastolic and systolic thickness, associated with approximately
2–fold increase in left ventricular (P)RR protein levels at 2 weeks. To test whether the worsening of cardiac function and
structure by (P)RR gen
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