Abstract
This chapter analyzes the role of hypoxia-inducible factor 1 (HIF-1) in the pathogenesis of hypoxic pulmonary hypertension. Many lung diseases are associated with reduced alveolar oxygen concentration, resulting in pulmonary hypertension and eventual right heart failure. The transcription factor HIF-1 plays a critical role in mediating adaptive responses to hypoxia. HIF-1 regulates the expression of dozens of genes important in growth, vascular development, and metabolism. A member of the basic helix–loop–helix family of proteins, HIF-1 is a heterodimer of HIF-1α and HIF-1β subunits. Whereas HIF-1β is expressed constitutively in the lung, HIF-1α protein expression is regulated by the inspired oxygen concentration. This chapter discusses the methods to quantify physiological changes that occur in the lung in response to alveolar hypoxia. Concepts related to animal model and hypoxic exposure, physiological measurements for right ventricle (RV) pressure, hematocrit, RV hypertrophy, and pulmonary vascular morphometry, pulmonary arterial smooth muscle cell (PASMC) isolation, and measurement of cell capacitance are described.
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