Totaro Pasquale, Tirelli Claudio, De Amici Mara, Grosjean Fabrizio, Testa Giorgia, Sacchi Lucia, De Silvestri Annalisa, Alloni Alessia, Kushta Eraldo, Albertini Riccardo, Rampino Teresa, D'Armini Andrea Maria
Division of Cardiac Surgery 2,Pulmonary Hypertension Center, Foundation I.R.C.C.S. Policlinico San Matteo, 27100 Pavia, Italy.
Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy.
J Clin Med. 2024 Aug 23;13(17):4977. doi: 10.3390/jcm13174977.
Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months ( < 0.001) and at 1 year ( = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses ( < 0.05). ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated.
内皮素-1（ET-1）和转化生长因子-β（TGF-β）在慢性血栓栓塞性肺动脉高压（CTEPH）的病理生理学和血管重塑中起关键作用，CTEPH是急性肺栓塞（PE）一种诊断不足的并发症。目前，肺动脉内膜剥脱术（PEA）仍是部分CTEPH患者的首选治疗方法。本研究旨在评估接受PEA成功手术治疗的CTEPH患者术前和术后循环中ET-1和TGF-β的水平。在意大利帕维亚圣马泰奥综合医院（IRCCS Policlinico San Matteo Hospital）接受PEA的CTEPH患者的数据被前瞻性地记录在机构数据库中。在PEA术前、术后3个月和1年，使用酶联免疫吸附测定（ELISA）商业试剂盒评估循环中ET-1和TGF-β水平。还记录了人口统计学数据、术前平均肺动脉压（mPAP）、心输出量（CO）和肺血管阻力（PVR）。进行了单因素和多因素分析。该分析包括340例有完整ET-1测量值的患者和206例有完整TGF-β测量值的患者。PEA术后3个月（<0.001）和1年（=0.009）时，ET-1均显著降低。另一方面，PEA术后术前TGF-β水平无显著变化。此外，在多因素分析中，ET-1而非TGF-β是mPAP升高的良好预测指标（<0.05）。在接受PEA的CTEPH患者中，直至术后1年，ET-1而非TGF-β受到显著调节。导致循环中TGF-β水平长期升高的机制及其临床意义有待进一步阐明。
