Premium
Molecular mechanisms of hypoxia‐inducible factor‐induced pulmonary arterial smooth muscle cell alterations in pulmonary hypertension
Author(s) -
Veith Christine,
Schermuly Ralph T.,
Brandes Ralf P.,
Weissmann Norbert
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270689
Subject(s) - hypoxia (environmental) , pulmonary hypertension , transcription factor , hypoxia inducible factors , pathophysiology , biology , muscle hypertrophy , pulmonary artery , lung , hypoxic pulmonary vasoconstriction , microbiology and biotechnology , medicine , cardiology , endocrinology , chemistry , oxygen , gene , biochemistry , organic chemistry
Oxygen (O 2 ) is essential for the viability and function of most metazoan organisms and thus is closely monitored at both the organismal and the cellular levels. However, alveoli often encounter decreased O 2 levels (hypoxia), leading to activation of physiological or pathophysiological responses in the pulmonary arteries. Such changes are achieved by activation of transcription factors. The hypoxia‐inducible factors (HIFs) are the most prominent hypoxia‐regulated transcription factors in this regard. HIFs bind to hypoxia‐response elements (HREs) in the promoter region of target genes, whose expression and translation allows the organism, amongst other factors, to cope with decreased environmental O 2 partial pressure (pO 2 ). However, prolonged HIF activation can contribute to major structural alterations, especially in the lung, resulting in the development of pulmonary hypertension (PH). PH is characterized by a rise in pulmonary arterial pressure associated with pulmonary arterial remodelling, concomitant with a reduced intravascular lumen area. Patients with PH develop right heart hypertrophy and eventually die from right heart failure. Thus, understanding the molecular mechanisms of HIF regulation in PH is critical for the identification of novel therapeutic strategies. This review addresses the relationship of hypoxia and the HIF system with pulmonary arterial dysfunction in PH. We particularly focus on the cellular and molecular mechanisms underlying the HIF‐driven pathophysiological processes.