Transcriptional responses to intermittent hypoxia

Area of Science:

• Cardiovascular Physiology
• Respiratory Physiology
• Molecular Biology

Background:

• Recurrent apneas cause chronic intermittent hypoxia (IH), leading to cardio-respiratory morbidities in patients and animals.
• Understanding the transcriptional mechanisms behind IH is crucial for addressing these health issues.

Purpose of the Study:

• To review current knowledge on transcriptional mechanisms activated by chronic intermittent hypoxia (IH).
• To compare IH-induced transcriptional activation with continuous hypoxia (CH).

Main Methods:

• Studies on rodents and cell cultures exposed to IH.
• Analysis of transcription factor activation (HIF-1, c-fos, NFAT, NF-kB).
• Investigation of signaling pathways, including reactive oxygen species (ROS).

Main Results:

• IH activates HIF-1, c-fos, NFAT, and NF-kB, differing from CH.
• IH causes more potent and prolonged accumulation of HIF-1alpha and c-fos mRNA than CH.
• IH-induced activation requires ROS-mediated signaling and involves HIF-1/ROS feed-forward interactions.

Conclusions:

• Cardio-respiratory responses to IH depend on complex interactions between transcription factors like HIF-1 and NFAT.
• Absence of HIF-1alpha or NFAT3c in mice negates IH-evoked cardio-respiratory responses and hypertension.
• These findings highlight intricate molecular pathways underlying IH-related pathologies.