PGC-1α plays a major role in the anti-apoptotic effect of 15-HETE in pulmonary artery endothelial cells

- PGC-1α expression increases under hypoxia in pulmonary artery endothelial cells.
- Hypoxia-induced PGC-1α is modulated by 15-HETE.
- PGC-1α mediates the anti-apoptotic effect of 15-HETE.
- PGC-1α regulates apoptosis via caspase and mitochondria pathway.

Peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) has been confirmed as a key regulatory factor in pulmonary artery smooth muscle cells to mediate mitochondrial biogenesis and proliferation during hypoxia. However, the functional role of PGC-1α in hypoxic pulmonary artery endothelial cells (PAECs) still needs to be determined. In the present study, we found a marked elevation in the expression of PGC-1α under hypoxia, which was predominate in the nucleus of PAECs. This alteration of PGC-1α showed a significant association with 15-Hydroxyeicosatetraenoic acid (15-HETE), a regulator known to be protective against apoptosis at the concentration of 1 μM. By silencing PGC-1α, the action against cell viability suppression induced by 15-HETE was blocked, not only in normoxic condition but also in hypoxia-stimulated condition. Likewise, the tendency to reduce TUNEL-positive cells, abnormal nuclei and apoptotic cells in response to 15-HETE was depending on PGC-1α. Furthermore, 15-HETE and PGC-1α siRNA caused significant alterations in related mechanisms including caspase activity, mitochondrial membrane potential, and Bcl-2 expression. Taken together, these results provide the first evidence to confirm the importance of PGC-1α in mediating the protective effect of 15-HETE against apoptosis. Therefore, a clear role of PGC-1α in hypoxic PAECs is demonstrated, which may be attributed to pulmonary vascular remodeling.