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The major characteristic pathological findings of pulmonary vascular remodelling are increased wall thickening of pulmonary vessels and mus- larization of small arteries. In laboratory animals, decreased ambient oxygen concentrations cause similar pathological findings, including pulmonary smooth muscle hypertrophy and proliferation [22,23]. It has been suggested that proliferation of pulmonary arterial smooth muscle cells (PASMC) is a key component of pulmonary vascular remodelling, and several in vitro studies have also addressed that exposure to hypoxia can stimulate prolife- tion of PASMC [13,4,1]. The proliferation of the PASMC begins when the cells enter into the cell cycle. The most important molecular event necessary for the progress of the cell cycle is phosphorylation of retinoblastoma protein by cyclin-dependent kinase (CDK)-cyclin complexes. The CDK activity can be inhibited by CDK inhibitors and the expression of CDK inhibitor is a major regulator of the transition between each phase of the cell cycle [7]. Previous studies have noted that CDK inhibitor p27 plays an important role in the inhibition of the CDK activity and proliferation in vascular smooth muscle cells [2,3]. The G1 phase in severe hypoxia is suggested to involve the CKI p27, because the expression of p27 increased in several cell-lines when they were exposed to extreme hypoxia [20,5]. Previous reports indicate that hypoxia decreases the p27 expression in the murine lung [23,24] and we found that PGI2 suppresses hypox- induced proliferation of PASMC and maintains p27 in PASMC [20].
Current research on molecular pathways affected by hypoxic exposure Pathophysiological understanding of the adaptation of the human body to oxygen deprivation High altitude as a public health problem Prevention of high altitude induced or associated diseases Treatment of high altitude illnesses
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Hypoxia is and remains a major public health issue in many populated mountainous areas all over the world. This book is directly derived from a NATO-sponsored international meeting on problems of high altitude medicine and biology, which was held on the shores of lake Issyk-Kul, in Kyrghyzstan, in 2006. Overall, the meeting was an ideal mix of cell biology, integrative physiology and medical applications.
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Introduction: 45 Years Of Mountain Medicine.- High Altitude Pulmonary Hypertension And Chronic Mountain Sickness-Reappraisal Of The Consensus On Chronic And Subacute High Altitude Diseases.- The Cellular Effects Of Hypoxia In The Pulmonary Circulation.- Angiogenesis And Chronic Hypoxic Pulmonary Hypertension.- Tetrahydrobiopterin And Pulmonary Hypertension.- Hypoxia-Induced Proliferation Of Human Pulmonary Arterial Smooth Muscle Cells (Pasmc) Is Involved In The Suppression Of Cyclin-Dependent Kinase Inhibitors, P21, P27 And P53.- Pulmonary Adaptation To High Altitude In Wild Mammals.- The Lung At High Altitude: Between Physiology And Pathology.- Sildenafil And Hypoxic Pulmonary Hypertension.- The Role Of Antioxidants In Modulation Of Acclimatization Processes.- Gene Polymorphisms And High Altitude Pulmonary Hypertension.- Genetic Factors In The Acute Response To Hypoxia In Animals Models.- Who Gets High Altitude Pulmonary Edema And Why?.- Effects Of Inhaled Nitric Oxide And Oxygen In High Altitude Pulmonary Edema.- Altered Autoregulation Of Cerebral Blood Flow In Hypoxia: Relevance To The Pathophysiology Of Acute Mountain Sickness.- Cardiac Limitation To Exercise Capacity At High Altitudes.- Pediatric High Altitude Heart Disease: A Hypoxic Pulmonary Hypertension Syndrome.- Clinical And Functional Features Of Chronic Obstructive Pulmonary Disease In The Highlanders Of Kyrgzstan.- Monitoring The Morphological And Functional Parameters Of Platelets In Patients With Thrombocytopenic Purpura During High Mountain Treatment.- Role Of Exogenous Hypoxia In Treatment Of Chronic Glomerulonephritis.- Atherogenesis Of Brain Vessels In Conditions Of Hypoxia In Kyrgyz Highlanders.- Particularities Of Neuropsychotropic Effects Of Mexidol In Various Altitude Conditions.- Influence Of High-Altitude Hypoxia On Adaptive And Non-Adaptive Structural Changes In The Vessels Of The Pulmonary Circulation.- Acute Oxygen Sensing Mechanisms.
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