State Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Nuclear Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Respir Res. 2023 Nov 6;24(1):270. doi: 10.1186/s12931-023-02565-5.
Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF.
Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague-Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and F-labelled FAP inhibitor-42 ([ F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively.
RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [ F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB.
RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [ F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation.
右心衰竭（RHF）是肺动脉高压（PH）的并发症，会增加死亡率，且与基础疾病无关。然而，RHF 的发展和进展过程尚不完全清楚。我们旨在开发有效的方法，用于 RHF 的早期诊断和精确评估。
通过肺动脉结扎（PAB）手术在 Sprague-Dawley（SD）大鼠中进行右心室（RV）压力超负荷，以诱导 RHF。在 PAB 后第 3 天、第 1 周、第 2 周、第 4 周和第 8 周进行超声心动图、右心导管检查、组织学染色、成纤维细胞激活蛋白（FAP）免疫荧光和 F 标记的 FAP 抑制剂-42([F]-FAPI-42)正电子发射断层扫描/计算机断层扫描（PET/CT）。在 PAB 后第 2 周和第 4 周分别进行 RNA 测序，以探索 PAB 组与假手术组之间的分子变化。
在 PAB 后第 2、4 和 8 周，通过右心导管检查和超声心动图发现 RV 血流动力学障碍加重，RV 功能下降。在 PAB 后 2 周至 8 周，可观察到 RV 心肌肥厚、纤维化和毛细血管稀疏。RNA 测序表明，在 PAB 后第 2 周和第 4 周，RV 中有 80 个上调基因和 43 个下调基因；基因本体论（GO）分析表明，纤维化是 RV 在压力超负荷下最显著的生物学过程。免疫荧光表明，FAP 在 PAB 后第 2 周至第 8 周在 RV 中上调；[F]-FAPI-42 PET/CT 显示，在 PAB 后第 2 周和第 4 周 RV 中 FAPI 摄取显著增加，在第 4 周和第 8 周进一步增加。
RV 功能逐渐下降，纤维化是压力超负荷后最显著的分子变化，[F]-FAPI-42 PET/CT 在 RV 纤维化评估中与组织病理学一样敏感和准确。
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