Abstract 20181: PTEN Is A Key Mediator Of Vascular Remodeling In Pulmonary Hypertension
Introduction: Pulmonary hypertension (PH) induces vascular remodeling and impairs cardiac function. In addition, PH, which is secondary to CHF, is a major hurdle in the management of cardiac failure. PTEN, a phosphatase-and-tensin homolog deleted on chromosome 10 and implicated in multiple advanced cancers, has been shown to have a causative role in vascular restenosis. The objective of the present study was to test our hypothesis that PTEN may be a key mediator of vascular remodeling in PH.
Methods: PH was induced in rats (male Sprague Dawley; N=6 per group) by three different methods: (i) Monocrotaline administration (60 mg/kg sc) - pharmacological;(ii) Hypoxic exposure (10% O2) - physiological; (iii) Ligation of left-anterior-descending (LAD) coronary artery - clinical. High-frequency ultrasound (ECHO) and micro-MRI were used to monitor cardiac function during the development of PH. Western-blot analysis was used to measure PTEN and other key downstream proteins involved in PH.
Results: All three methods resulted in the development of PH in 2–4 weeks as verified by RV systolic pressure monitoring. Noninvasive serial imaging studies showed a significant deterioration of cardiac function, particularly LV-EF (37% vs 75% in control). Phosphorylated PTEN was markedly decreased to 45.1% in lung, 59.5% in LV, 37.2% in RV when compared to respective tissues in control. In contrast, pAkt levels were significantly upregulated in the tissues of the PH group (341% lung, 157% LV, 128% in RV).
Conclusions: The study showed that PH was associated with reduction of PTEN levels in the cardiac and pulmonary tissues. The study suggests that PTEN may be a potential target for the management of PH.
- © 2010 by American Heart Association, Inc.