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Pulmonary hypertension induced by right pulmonary artery occlusion: Hemodynamic consequences of BMPR2 mutation.

التفاصيل البيبلوغرافية
العنوان: Pulmonary hypertension induced by right pulmonary artery occlusion: Hemodynamic consequences of BMPR2 mutation.
المؤلفون: Grynblat, J., Todesco, A., Akoumia, F.K., Bonnet, D., Mendes-Ferreira, P., Meot, M., Vastel-Amzallag, C., Malekzadeh-Milani, S., Decante, B., Levy, M., Morisset, S., Humbert, M., Montani, D., Boulate, D., Perros, F.
المصدر: Archives of Cardiovascular Diseases; 2024 Supplement, Vol. 117 Issue 8/9, pS228-S228, 1p
مستخلص: The primary genetic risk factor for heritable pulmonary arterial hypertension (PAH) is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for PAH occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, while the redirection of blood flow to unobstructed arteries lead to endothelial dysfunction and vascular remodeling. We aimed to evaluate the effect of right pulmonary artery occlusion (RPAO) in rats. Then, we evaluated the effect of BMPR2 loss of function on cardiac and pulmonary vascular remodeling. Male and female rats with a 71 bp monoallelic deletion in exon 1 of BMPR2 and their wild-type (WT) siblings underwent acute and chronic RPAO. They were subjected to full high-fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced pre-capillary PH in male and female rats, both acutely and chronically. BMPR2 mutant and male rats manifested more severe PH compared to their counterparts. While WT rats adapted to RPAO, BMPR2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male BMPR2 rats. Chronic RPAO resulted in elevated pulmonary interleukin-6 (IL-6) expression and decreased Gdf2 expression (corrected P -value < 0.05 and log2 fold change > 1). In this context, male rats expressed higher pulmonary levels of endothelin-1 and IL-6 than females (Fig. 1). Our novel two-hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex and gene-related effects. [ABSTRACT FROM AUTHOR]
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