eNOS Uncoupling-ER Stress-Mitochondrial Dysfunction Axis in the Development of Pulmonary Hypertension - PubMed
4 hours ago
- #pulmonary hypertension
- #mitochondrial dysfunction
- #eNOS uncoupling
- Pulmonary hypertension (PH) was induced in models using 2,4-diamino 6-hydroxypyrimidine (DAHP) or hypoxia exposure.
- Interventions with folic acid (attenuating eNOS uncoupling) or phenylbutyric acid (abrogating ER stress) reduced mean pulmonary arterial pressure, vascular remodeling, superoxide production, and eNOS uncoupling, while preserving NO bioavailability.
- Scavenging mitochondrial reactive oxygen species with MitoTempo abolished molecular and pathophysiological features of PH.
- Treatments with folic acid, phenylbutyric acid, or their combination mitigated mitochondrial swelling and distortion of mitochondrial cristae.
- The study establishes a novel eNOS uncoupling/ER stress/mitochondrial dysfunction axis as a key mechanism in PH development, suggesting potential therapeutic targets.