Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung

Yazhini Ravi, Karuppaiyah Selvendiran, Shan K. Naidu, Sarath Meduru, Lucas A. Citro, Balázs Bognár, Mahmood Khan, T. Kalai, K. Hideg, Periannan Kuppusamy, Chittoor B. Sai-Sudhakar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 Hg: 35.9±1.8 versus 14.8±2.0, control; P

Original languageEnglish
Pages (from-to)593-601
Number of pages9
JournalHypertension
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Peroxynitrous Acid
Pulmonary Hypertension
Down-Regulation
Heart Failure
Lung
Pulmonary Artery
Smooth Muscle Myocytes
Cell Proliferation
Pressure
Chromosomes, Human, Pair 10
Vascular Smooth Muscle
Phosphoric Monoester Hydrolases
Ligation
Real-Time Polymerase Chain Reaction
Coronary Vessels
Hemodynamics
Western Blotting

Keywords

  • HO-3867
  • left-heart failure
  • peroxynitrite
  • phosphatase-and-tensin homolog on chromosome 10
  • pulmonary hypertension

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Ravi, Y., Selvendiran, K., Naidu, S. K., Meduru, S., Citro, L. A., Bognár, B., ... Sai-Sudhakar, C. B. (2013). Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung. Hypertension, 61(3), 593-601. https://doi.org/10.1161/HYPERTENSIONAHA.111.00514

Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung. / Ravi, Yazhini; Selvendiran, Karuppaiyah; Naidu, Shan K.; Meduru, Sarath; Citro, Lucas A.; Bognár, Balázs; Khan, Mahmood; Kalai, T.; Hideg, K.; Kuppusamy, Periannan; Sai-Sudhakar, Chittoor B.

In: Hypertension, Vol. 61, No. 3, 03.2013, p. 593-601.

Research output: Contribution to journalArticle

Ravi, Y, Selvendiran, K, Naidu, SK, Meduru, S, Citro, LA, Bognár, B, Khan, M, Kalai, T, Hideg, K, Kuppusamy, P & Sai-Sudhakar, CB 2013, 'Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung', Hypertension, vol. 61, no. 3, pp. 593-601. https://doi.org/10.1161/HYPERTENSIONAHA.111.00514
Ravi, Yazhini ; Selvendiran, Karuppaiyah ; Naidu, Shan K. ; Meduru, Sarath ; Citro, Lucas A. ; Bognár, Balázs ; Khan, Mahmood ; Kalai, T. ; Hideg, K. ; Kuppusamy, Periannan ; Sai-Sudhakar, Chittoor B. / Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung. In: Hypertension. 2013 ; Vol. 61, No. 3. pp. 593-601.
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