[(18) F] -FAPI-42 PET/CT assessment of Progressive right ventricle fibrosis under pressure overload.
[(18) F] -FAPI-42 PET/CT assessment of Progressive right ventricle fibrosis under pressure overload.
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DOI：
10.1186/s12931-023-02565-5
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发表时间：
2023-11-06
影响因子：
5.8
通讯作者：
Wang, Tao
中科院分区：
文献类型：
--
作者：
Zeng, Xiaohui;Zhao, Ruiyue;Wu, Zhixiong;Ma, Zhuoji;Cen, Chunxian;Gao, Shanshan;Hong, Wanxian;Yao, Yanrong;Wen, Kexin;Ding, Shangwei;Wang, Jian;Lu, Wenju;Wang, Xinlu;Wang, Tao
右心衰（RHF）是肺动脉高压（PH）的并发症，与潜在疾病无关，可增加死亡率。然而，RHF的发展和进展过程尚不完全清楚。我们的目标是开发早期诊断和精确评估RHF的有效方法。采用肺动脉束带（PAB）术对SD大鼠右心室（RV）压力过载诱导RHF。在PAB后第3天、第1、2、4和8周进行超声心动图、右心导管检查、组织学染色、成纤维细胞活化蛋白（FAP）免疫荧光和18f标记FAP抑制剂-42 （[18f] -FAPI-42）正电子发射断层扫描/计算机断层扫描（PET/CT）。分别在PAB后第2周和第4周进行RNA测序，观察PAB组和假手术组之间的分子变化。左室血流动力学障碍加重，右心导管和超声心动图显示右室功能在PAB后第2、4和8周下降。PAB后2 ~ 8周，左室可观察到进行性心肌肥大、纤维化和毛细血管稀疏。RNA测序显示，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（Gene Ontology， GO）分析显示，在压力过载下，纤维化是右心室最重要的生物学过程。免疫荧光显示PAB后第2周至第8周，RV中FAP表达上调；[18 F] -FAPI-42 PET/CT显示，第2周RV的FAPI摄取明显增加，PAB后第4周和第8周进一步增加。压力过载后右心室功能逐渐下降，纤维化是最突出的分子变化，[18 F] -FAPI-42 PET/CT在右心室纤维化评估中与组织病理学一样敏感和准确。在线版本包含补充材料，可在10.1186/s12931-023-02565-5获得。
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 18 F-labelled FAP inhibitor-42 ([18 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 [18 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 [18 F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation. The online version contains supplementary material available at 10.1186/s12931-023-02565-5.
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DOI：
10.1055/s-0031-1298019
发表时间：
2012-03
期刊：
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
影响因子：
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