Résumé
As the average age in many countries steadily rises, heart infarction, stroke, and cancer become the most common causes of death in the 21st century. The causes of these disorders are many and varied and include genetic predisposition and environmental influences, but they all share a common feature in that limitation of oxygen availability participates in the development of these pathological conditions. However, cells and organisms are able to trigger an adaptive response to hypoxic conditions that is aimed to help them to cope with these threatening conditions. This review provides a description of several systems able to sense oxygen concentration and of the responses they initiate both in the acute and also in long-term hypoxia adaptation. The role of hypoxia in three pathological conditions, myocardial and cerebral ischemia as well as tumorigenesis, is briefly discussed.
The ability to maintain oxygen homeostasis is essential to the survival of all vertebrate species. Physiological systems have evolved to ensure the optimal oxygenation of all cells in each organism. This occurred through the evolution of a complex physiological infrastructure for O2 delivery that includes an entry (lungs), transport vehicle (erythrocytes), a highway and secondary road system (vasculature), and a propulsion device (heart). The precise establishment of these systems during development and their regulation in organisms provide the basis for oxygen homeostasis.
Sensing of increased (hyperoxia) or decreased (hypoxia) O2 level occurs through specialized chemoreceptor cells that regulate cardiovascular and ventilatory rates. In addition, all nucleated cells sense O2 concentration and respond to reduced O2 availability acutely (within minutes) through the activation of pre-existing proteins and chronically (within hours) through the regulation of gene transcription. The first part of this review will provide a description of these systems. Not only is O2 homeostasis essential for survival, but hypoxia plays also an important role in the pathogenesis of frequent and severe pathologies including myocardial and cerebral ischemia and cancer. In the second part of the review, the role of hypoxia in these pathological conditions will be described.
The ability to maintain oxygen homeostasis is essential to the survival of all vertebrate species. Physiological systems have evolved to ensure the optimal oxygenation of all cells in each organism. This occurred through the evolution of a complex physiological infrastructure for O2 delivery that includes an entry (lungs), transport vehicle (erythrocytes), a highway and secondary road system (vasculature), and a propulsion device (heart). The precise establishment of these systems during development and their regulation in organisms provide the basis for oxygen homeostasis.
Sensing of increased (hyperoxia) or decreased (hypoxia) O2 level occurs through specialized chemoreceptor cells that regulate cardiovascular and ventilatory rates. In addition, all nucleated cells sense O2 concentration and respond to reduced O2 availability acutely (within minutes) through the activation of pre-existing proteins and chronically (within hours) through the regulation of gene transcription. The first part of this review will provide a description of these systems. Not only is O2 homeostasis essential for survival, but hypoxia plays also an important role in the pathogenesis of frequent and severe pathologies including myocardial and cerebral ischemia and cancer. In the second part of the review, the role of hypoxia in these pathological conditions will be described.
langue originale | Anglais |
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Pages (de - à) | 1875-1882 |
Nombre de pages | 8 |
journal | The American Journal of Pathology |
Volume | 164 |
Numéro de publication | 6 |
Etat de la publication | Publié - 2004 |