Identification of LTBP-2 as a plasma biomarker for right ventricular dysfunction in human pulmonary arterial hypertension
Identification of LTBP-2 as a plasma biomarker for right ventricular dysfunction in human pulmonary arterial hypertension
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DOI：
10.1038/s44161-022-00113-w
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发表时间：
2022-08-01
期刊：
影响因子：
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通讯作者：
Bonnet, Sebastien
中科院分区：
文献类型：
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作者：
Boucherat, Olivier;Yokokawa, Tetsuro;Bonnet, Sebastien
虽然右心室（RV）功能是肺动脉高压（PAH）发病率和死亡率的主要决定因素，但右心室重塑的分子机制和反映其功能的循环因子在很大程度上仍然是未知的。在此背景下，识别与非适应性RV重构相关的新分子以及优化PAH的风险分层方法是关键的优先事项。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学分析相结合，我们发现了一组主要与心脏纤维化相关的蛋白质，这些蛋白质在PAH合并失代偿性RV患者的RV和血浆中同样上调。其中，我们证明了血浆潜伏转化生长因子β结合蛋白2 （LTBP-2）水平与人类PAH的RV功能相关，并为目前的风险分层模型增加了增加价值，以预测两个独立的PAH队列的长期生存。Bonnet等人将加拿大肺动脉高压（PAH）患者的右心室组织转录组学和蛋白质组学分析与血浆蛋白质组学分析相结合，发现了PAH患者中与右心室功能障碍相关的新循环蛋白。
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.Through a combination of transcriptomic and proteomic profiling of human right ventricle tissue with plasma proteome profiling in a Canadian cohort of patients with pulmonary arterial hypertension (PAH), Bonnet et al. discovered new circulating proteins associated with right ventricular dysfunction in the setting of PAH.