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Dysregulation of PTEN in Cardiopulmonary Vascular Remodeling Induced by Pulmonary Hypertension
by
Sai-Sudhakar, Chittoor B.
, Khan, Mahmood
, Meduru, Sarath
, Rivera, Brian K.
, Ravi, Yazhini
, Selvendiran, Karuppaiyah
, Citro, Lucas
, Naidu, Shan
, Kuppusamy, Periannan
in
Animal tissues
/ Animals
/ Biochemistry
/ Biological and Medical Physics
/ Biomedical and Life Sciences
/ Biophysics
/ Biotechnology
/ Cell Biology
/ Cell Cycle Proteins - metabolism
/ Cell Proliferation - drug effects
/ Gene Expression Regulation - drug effects
/ Heart - physiopathology
/ Histopathology
/ Humans
/ Hypertension
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypertension, Pulmonary - pathology
/ Hypertension, Pulmonary - physiopathology
/ Hypoxia
/ Hypoxia - complications
/ Life Sciences
/ Lung - pathology
/ Lung - physiopathology
/ Monocrotaline - pharmacology
/ Myocardium - pathology
/ Myocytes, Smooth Muscle - metabolism
/ Myocytes, Smooth Muscle - pathology
/ Original Paper
/ Oxidative stress
/ Pharmacology/Toxicology
/ Proteasome Endopeptidase Complex - metabolism
/ Proteolysis - drug effects
/ PTEN Phosphohydrolase - genetics
/ PTEN Phosphohydrolase - metabolism
/ Rats
2013
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Dysregulation of PTEN in Cardiopulmonary Vascular Remodeling Induced by Pulmonary Hypertension
by
Sai-Sudhakar, Chittoor B.
, Khan, Mahmood
, Meduru, Sarath
, Rivera, Brian K.
, Ravi, Yazhini
, Selvendiran, Karuppaiyah
, Citro, Lucas
, Naidu, Shan
, Kuppusamy, Periannan
in
Animal tissues
/ Animals
/ Biochemistry
/ Biological and Medical Physics
/ Biomedical and Life Sciences
/ Biophysics
/ Biotechnology
/ Cell Biology
/ Cell Cycle Proteins - metabolism
/ Cell Proliferation - drug effects
/ Gene Expression Regulation - drug effects
/ Heart - physiopathology
/ Histopathology
/ Humans
/ Hypertension
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypertension, Pulmonary - pathology
/ Hypertension, Pulmonary - physiopathology
/ Hypoxia
/ Hypoxia - complications
/ Life Sciences
/ Lung - pathology
/ Lung - physiopathology
/ Monocrotaline - pharmacology
/ Myocardium - pathology
/ Myocytes, Smooth Muscle - metabolism
/ Myocytes, Smooth Muscle - pathology
/ Original Paper
/ Oxidative stress
/ Pharmacology/Toxicology
/ Proteasome Endopeptidase Complex - metabolism
/ Proteolysis - drug effects
/ PTEN Phosphohydrolase - genetics
/ PTEN Phosphohydrolase - metabolism
/ Rats
2013
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Dysregulation of PTEN in Cardiopulmonary Vascular Remodeling Induced by Pulmonary Hypertension
by
Sai-Sudhakar, Chittoor B.
, Khan, Mahmood
, Meduru, Sarath
, Rivera, Brian K.
, Ravi, Yazhini
, Selvendiran, Karuppaiyah
, Citro, Lucas
, Naidu, Shan
, Kuppusamy, Periannan
in
Animal tissues
/ Animals
/ Biochemistry
/ Biological and Medical Physics
/ Biomedical and Life Sciences
/ Biophysics
/ Biotechnology
/ Cell Biology
/ Cell Cycle Proteins - metabolism
/ Cell Proliferation - drug effects
/ Gene Expression Regulation - drug effects
/ Heart - physiopathology
/ Histopathology
/ Humans
/ Hypertension
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypertension, Pulmonary - pathology
/ Hypertension, Pulmonary - physiopathology
/ Hypoxia
/ Hypoxia - complications
/ Life Sciences
/ Lung - pathology
/ Lung - physiopathology
/ Monocrotaline - pharmacology
/ Myocardium - pathology
/ Myocytes, Smooth Muscle - metabolism
/ Myocytes, Smooth Muscle - pathology
/ Original Paper
/ Oxidative stress
/ Pharmacology/Toxicology
/ Proteasome Endopeptidase Complex - metabolism
/ Proteolysis - drug effects
/ PTEN Phosphohydrolase - genetics
/ PTEN Phosphohydrolase - metabolism
/ Rats
2013
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Dysregulation of PTEN in Cardiopulmonary Vascular Remodeling Induced by Pulmonary Hypertension
Journal Article
Dysregulation of PTEN in Cardiopulmonary Vascular Remodeling Induced by Pulmonary Hypertension
2013
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Overview
Pulmonary hypertension (PH) is a disorder of lung vasculature characterized by arterial narrowing. Phosphatase-and-tensin homolog on chromosome 10 (PTEN), associated in the progression of multiple cancers, is implicated in arterial remodeling. However, the involvement of PTEN in PH remains unclear. The objective of the present study was to determine the role of PTEN in pulmonary vascular remodeling using established models of PH. The study used rat models of PH, induced by monocrotaline (MCT) administration (60 mg/kg) or continuous hypoxic exposure (10% oxygen) for 3 weeks. Pulmonary artery smooth muscle cells (SMCs) were used for in vitro confirmation. Development of PH was verified by hemodynamic, morphological and histopathology analyses. PTEN and key downstream proteins in pulmonary and cardiac tissues were analyzed by western blotting and RT-PCR. PTEN was significantly decreased (MCT, 53%; Hypoxia, 40%), pAkt was significantly increased (MCT, 42%; Hypoxia, 55%) in tissues of rats with PH. Similar results were observed in SMCs exposed to hypoxia (1% oxygen) for 48 h. Ubiquitination assay showed that PTEN degradation occurs via proteasomal degradation pathway. Western blotting demonstrated a significant downregulation of cell-cycle regulatory proteins p53 and p27, and upregulation of cyclin-D1 in the lungs of both models. The results showed that PTEN-mediated modulation of PI3K pathway was independent of the focal adhesion kinase and fatty acid synthase. The study, for the first time, established that PTEN plays a key role in the progression of pulmonary hypertension. The findings may have potential for the treatment of pulmonary hypertension using PTEN as a target.
Publisher
Springer US,Springer Nature B.V
Subject
/ Animals
/ Biological and Medical Physics
/ Biomedical and Life Sciences
/ Cell Cycle Proteins - metabolism
/ Cell Proliferation - drug effects
/ Gene Expression Regulation - drug effects
/ Humans
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypertension, Pulmonary - pathology
/ Hypertension, Pulmonary - physiopathology
/ Hypoxia
/ Monocrotaline - pharmacology
/ Myocytes, Smooth Muscle - metabolism
/ Myocytes, Smooth Muscle - pathology
/ Proteasome Endopeptidase Complex - metabolism
/ PTEN Phosphohydrolase - genetics
/ PTEN Phosphohydrolase - metabolism
/ Rats
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