Pulmonary Hypertension Secondary to Left-Heart Failure Involves Peroxynitrite-Induced Downregulation of PTEN in the Lung
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Tartalom: http://real.mtak.hu/20273/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published

Type = Article
Cím:
Pulmonary Hypertension Secondary to Left-Heart Failure Involves Peroxynitrite-Induced Downregulation of PTEN in the Lung
Létrehozó:
Ravi, Yazhini
Selvendrian, Karuppaiyah
Naidu, Shan
Meduru, Sarath
Citro, Lucas
Bognár, Balázs
Khan, Mahmood
Kálai, Tamás
Kuppusamy, Periannan
Sai-Sudhakar, Chittoor B.
Dátum:
2013
Téma:
RC Internal medicine / belgyógyászat
Tartalmi leírás:
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<0.001) and vascular remodeling. HO-3867 treatment decreased mean pulmonary
artery pressure to 22.6±0.8 mm Hg (P<0.001). Substantially higher levels of peroxynitrite and significant loss of
PTEN expression were observed in the lungs of LHF rats when compared with control. In vitro studies using human
pulmonary artery SMCs implicated peroxynitrite-mediated downregulation of PTEN expression as a key mechanism
of SMC proliferation. The results further established that HO-3867 attenuated LHF-PH by decreasing oxidative stress
and increasing PTEN expression in the lung. In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation
seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF. (Hypertension.
2013;61:593-601.)
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Ravi, Yazhini and Selvendrian, Karuppaiyah and Naidu, Shan and Meduru, Sarath and Citro, Lucas and Bognár, Balázs and Khan, Mahmood and Kálai, Tamás and Kuppusamy, Periannan and Sai-Sudhakar, Chittoor B. (2013) Pulmonary Hypertension Secondary to Left-Heart Failure Involves Peroxynitrite-Induced Downregulation of PTEN in the Lung. HYPERTENSION, 61. pp. 593-601. ISSN 0194-911X
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