Abstract 14082: Pulmonary Hypertension With Thickening of Adventitial Area due to Decreased eNOS Bioavailability in Senescence Marker Protein-30 Knock-out Mice
Background: Senescence marker protein (SMP) -30 is known as an anti-aging protein. Recently, we have reported that endothelium-dependent vasodilation of the coronary artery is reduced in SMP-30 knock-out mice. In the hind limb ischemia model of SMP-30 knock-out mice, development of collateral vessels is impaired because of decreased vioavailability of endothelial nitric oxide synthase (eNOS). These results strongly suggest that SMP-30 affects the eNOS function in aging. It is widely known that eNOS is implicated in pathophysiology of pulmonary hypertension. However, the role of SMP-30 on pulmonary vessels is still unclear. In this study, we examined the role of the SMP-30 in pulmonary hypertension and its mechanism using the SMP-30 knock-out mice.
Methods: We used SMP-30 knock-out mice at the age of 20 to 25 weeks. We measured right ventricular systolic pressure (RVSP) by a micro-manometer catheter inserted from jugular vein and the ratio of right ventricular weight to left ventricular weight including ventricular septum (RV/LV). Hisotological examination of the lungs was carried out by Elastica-Masson staining. The medial area and the adventitial area of pulmonary arteriole were expressed by the ratio to the total vessel area. Levels of eNOS and phosphorylated-eNOS in lung tissue were analyzed by Western blotting.
Results: Increased RVSP was observed in the SMP-30 knock-out mice compared to wild type littermate (WT) mice (28.8 ± 7.0 vs. 18.8 ± 2.6 mmHg, P < 0.05). RV/LV was higher in the SMP30 knock-out mice than in WT mice (0.26 ± 0.07 vs. 0.17 ± 0.02, P < 0.05). There was significant increase in the adventitial area of pulmonary arteriole, but not medial area, in SMP-30 knock-out mice compared to WT mice (45.2 ± 3.6 vs. 35.1 ± 1.4%, P < 0.05). Additionally, in the lung tissue of SMP-30 knock-out mice, reduced eNOS phosphorylation was observed (relative intensity of immunoblots, 0.05 ± 0.03 vs. 0.18 ± 0.08, P < 0.05).
Conclusion: In this study, we found that SMP-30 deficiency caused pulmonary hypertension due to endothelial dysfunction including decreased phosphorylation of eNOS in lung tissue. SMP-30 may become a key molecule for considering the development of pulmonary hypertension in aging.
Author Disclosures: K. Sugimoto: Other; Significant; Author belongs to endowed department sponsored by Acterion Pharmaceuticals Japan. A. Sato: None. S. Watanabe: None. S. Suzuki: None. H. Suzuki: None. S. Saitoh: None. Y. Takeishi: None.
- © 2016 by American Heart Association, Inc.