Key result
Repeated autologous blood clot embolization in rats significantly increased mean pulmonary arterial pressure to 27.11 mmHg at 4 weeks and induced vascular remodeling, associated with decreased FoxO1 and Bcl-2 and increased Bad expression.
Why the study?
What is the role of FoxO1 and apoptosis in pulmonary vascular remodeling in a rat model of chronic thromboembolic pulmonary hypertension?
What is the role of FoxO1 and apoptosis in pulmonary vascular remodeling in a rat model of chronic thromboembolic pulmonary hypertension?
p-value: p=<0.05
FoxO1 and apoptosis-related proteins are altered in a rat model of CTEPH, suggesting their involvement in pulmonary vascular remodeling.
FoxO1 downregulation may drive apoptosis in CTEPH remodeling; leaves open its role as therapeutic target pending human studies.
To explore the role of FoxO1 and apoptosis in a rat model of chronic thromboembolic pulmonary hypertension (CTEPH). Rats were randomly divided into a sham group (n = 45) and an experimental group (n = 45). Autologous blood clots were injected into rats three times to induce CTEPH. Rats were further divided into three subgroups: a 1-week subgroup (n = 15), a 2-week subgroup (n = 15), and a 4-week subgroup (n = 15). Mean pulmonary arterial pressure (mPAP) and histopathology were evaluated at each time point. FoxO1, Bad, and Bcl-2 levels were examined at each time point using reverse transcription PCR and western blotting. The mPAP and vessel wall area/total area (WA/TA) ratio in the experimental group gradually increased in a time-dependent manner (P < 0.05). Both the mRNA and protein levels of FoxO1 decreased in the CTEPH rats compared to in the sham group. In addition, embolization led to the up-regulation of Bad and the down-regulation of Bcl-2 (P < 0.05). FoxO1 and apoptosis play an important role in the pathogenesis of CTEPH. Apoptosis-resistant pulmonary artery endothelial cells may play an important role in remodeling of the rat pulmonary artery.
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Deng et al. (2017) studied Chronic thromboembolic pulmonary hypertension (CTEPH) (n=90). Repeated autologous blood clot embolization vs. Sham (normal saline) was evaluated on Mean pulmonary arterial pressure (mPAP) at 4 weeks (p=<0.05). Repeated autologous blood clot embolization in rats significantly increased mean pulmonary arterial pressure to 27.11 mmHg at 4 weeks and induced vascular remodeling, associated with decreased FoxO1 and Bcl-2 and increased Bad expression.
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