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. 2024 Aug 23;13(17):4977.
doi: 10.3390/jcm13174977.

Circulating Endothelin 1 but Not Transforming Growth Factor-β Levels Are Reduced after Pulmonary Endarterectomy in Subjects Affected by Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study

Pasquale Totaro  1 , Claudio Tirelli  2 , Mara De Amici  3 , Fabrizio Grosjean  4 , Giorgia Testa  5 , Lucia Sacchi  6 , Annalisa De Silvestri  7 , Alessia Alloni  4 , Eraldo Kushta  1 , Riccardo Albertini  3 , Teresa Rampino  4 , Andrea Maria D'Armini  1
Affiliations

Circulating Endothelin 1 but Not Transforming Growth Factor-β Levels Are Reduced after Pulmonary Endarterectomy in Subjects Affected by Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study

Pasquale Totaro et al. J Clin Med. .

Abstract

Background and objectives: 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. Methods: 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. Results: 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 (p < 0.001) and at 1 year (p = 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 (p < 0.05). Conclusions: 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.

Keywords: chronic thromboembolic pulmonary hypertension; endothelin 1; mean pulmonary arterial pressure; pulmonary endarterectomy; transforming growth factor-β.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Box and whiskers plot of preoperative ET-1 (A) and TGF-β (B) levels according to patient demographic characteristics (a,b); extension of diseases (c); and clinical status (d).
Figure 2
Figure 2
Box and whiskers plot of ET-1 (a) or TGF-β (b) levels in preoperative samples, at 3 months and 1 year after PEA.
Figure 3
Figure 3
Box and whiskers plot of ET-1 postoperative drop according to patient’s gender (a), extension of disease (b), and hemodynamic and clinical parameters (c,d). ET1 early drop: ET-1 drop at hospital discharge; T2 drop: ET-1 value drop from discharge to 3-month follow-up; 3 m drop: ET-1 value cumulative drop from preoperative to 3-month follow-up.
Figure 4
Figure 4
Long-term (>15 years) survival following PEA according to preoperative value of plasma ET-1 (a) and serum TGF-β (b).
Figure 5
Figure 5
Long-term (>15 years) survival following PEA according to ET-1 postoperative drop at 3 months (a) and preoperative extent of disease (b).
See this image and copyright information in PMC

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