Pulmonary Hypertension Secondary to Left-Heart Failure Involves Peroxynitrite-Induced Downregulation of PTEN in the Lung

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2013-03, Vol.61 (3), p.593-601
• Main Authors: Ravi, Yazhini, Selvendiran, Karuppaiyah, Naidu, Shan K, Meduru, Sarath, Citro, Lucas A, Bognár, Balázs, Khan, Mahmood, Kálai, Tamás, Hideg, Kálmán, Kuppusamy, Periannan, Sai-Sudhakar, Chittoor B
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Line; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Down-Regulation - physiology; Heart Failure - complications; Heart Failure - diagnostic imaging; Heart Failure - drug therapy; Heart Failure - metabolism; Humans; Hypertension, Pulmonary - diagnostic imaging; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Lung - blood supply; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Medical sciences; Microvessels - drug effects; Microvessels - metabolism; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Oxidative Stress - drug effects; Peroxynitrous Acid - analysis; Peroxynitrous Acid - metabolism; Piperidones - therapeutic use; PTEN Phosphohydrolase - biosynthesis; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Rats; Rats, Sprague-Dawley; Ultrasonography
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.111.00514

Pulmonary hypertension (PH) that occurs after left-heart failure (LHF), classified as Group 2 PH, involves progressive pulmonary vascular remodeling induced by smooth muscle cell (SMC) proliferation. However, mechanisms involved in the activation of SMCs remain unknown. The objective of this study was to determine the involvement of peroxynitrite and phosphatase-and-tensin homolog on chromosome 10 (PTEN) in vascular SMC proliferation and remodeling in the LHF-induced PH (LHF-PH). LHF was induced by permanent ligation of left anterior descending coronary artery in rats for 4 weeks. MRI, ultrasound, and hemodynamic measurements were performed to confirm LHF and PH. Histopathology, Western blot, and real-time polymerase chain reaction analyses were used to identify key molecular signatures. Therapeutic intervention was demonstrated using an antiproliferative compound, HO-3867. LHF-PH was confirmed by significant elevation of pulmonary artery pressure (mean pulmonary artery pressure/mm Hg35.9±1.8 versus 14.8±2.0, control; P