Boucherat Olivier, Yokokawa Tetsuro, Krishna Vinod, Kalyana-Sundaram Shanker, Martineau Sandra, Breuils-Bonnet Sandra, Azhar Nabil, Bonilla Fany, Gutstein David, Potus François, Lawrie Allan, Jeyaseelan Jey, Provencher Steeve, Bonnet Sebastien
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Québec, Canada.
Department of Medicine, Université Laval, Québec City, Québec, Canada.
Nat Cardiovasc Res. 2022 Aug;1(8):748-760. doi: 10.1038/s44161-022-00113-w. Epub 2022 Aug 11.
Although right ventricular (RV) function is the primary determinant of morbidity and mortality in pulmonary arterial hypertension (PAH), the molecular mechanisms of RV remodeling and the circulating factors reflecting its function remain largely elusive. In this context, the identification of new molecular players implicated in maladaptive RV remodeling along with the optimization of risk stratification approaches in PAH are key priorities. Through combination of transcriptomic and proteomic profiling of RV tissues with plasma proteome profiling, we identified a panel of proteins, mainly related to cardiac fibrosis, similarly upregulated in the RV and plasma of patients with PAH with decompensated RV. Among these, we demonstrated that plasma latent transforming growth factor beta binding protein 2 (LTBP-2) level correlates with RV function in human PAH and adds incremental value to current risk stratification models to predict long-term survival in two independent PAH cohorts.
尽管右心室（RV）功能是肺动脉高压（PAH）发病和死亡的主要决定因素，但RV重塑的分子机制以及反映其功能的循环因子在很大程度上仍不清楚。在此背景下，确定与适应性不良的RV重塑相关的新分子参与者以及优化PAH的风险分层方法是关键优先事项。通过将RV组织的转录组学和蛋白质组学分析与血浆蛋白质组分析相结合，我们鉴定出一组主要与心脏纤维化相关的蛋白质，在失代偿性RV的PAH患者的RV和血浆中同样上调。其中，我们证明血浆潜伏转化生长因子β结合蛋白2（LTBP-2）水平与人类PAH中的RV功能相关，并为当前风险分层模型增加了预测两个独立PAH队列长期生存的增量价值。
