Potential biomarkers and targets in reversibility of pulmonary arterial hypertension secondary to congenital heart disease: an explorative study.
Potential biomarkers and targets in reversibility of pulmonary arterial hypertension secondary to congenital heart disease: an explorative study.
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DOI：
10.1177/2045893218755987
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发表时间：
2018-04
影响因子：
2.6
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Huang L;Li L;Hu E;Chen G;Meng X;Xiong C;He J
肺动脉高压（PAH）在先天性心脏病（CHD）中是否可逆是影响冠心病手术可操作性的重要因素。然而，人们对此知之甚少。我们的研究旨在探索冠心病-多环芳烃可逆性的新生物标志物和靶点。纳入诊断为右心导管（RHC）的冠心病-肺动脉高压患者（n = 14）。修复术中行肺活检。随访1年后，通过RHC评估平均肺动脉压（mPAP），确定可逆性（mPAP < 25 mmHg, n = 10）和不可逆性（mPAP≥25 mmHg, n = 4） PAH的诊断。取正常肺组织（n = 6）作为对照组。组织染色病理分级确定肺小动脉病变。采用itraq标记的质谱分析、免疫组织化学和western blot方法探索最有意义的差异蛋白。在入组患者中，可逆性冠心病- pah患者肺血管病变的组织病理学分级均为0-II级，而III-IV级仅在不可逆性冠心病- pah患者中出现。蛋白质组学分析鉴定出85个上调蛋白和75个下调蛋白，包括细胞骨架蛋白和胶原链，主要参与细胞粘附、细胞外基质、细胞骨架、免疫应答和补体途径。其中，caveolin-1、丝蛋白A表达、组织蛋白酶D联合巨噬细胞计数显著升高；不可逆CHD-PAH组谷胱甘肽s -转移酶mu1 （GSTM1）表达显著降低（均P < 0.05）。Caveolin-1、丝蛋白A、组织蛋白酶D的表达与病理分级呈正相关，GSTM1呈负相关。小囊蛋白-1、丝蛋白A和组织蛋白酶D的上调与巨噬细胞的增加和GSTM1的下调可能是不可逆性冠心病- pah的潜在生物标志物和靶点，这可能有助于评估冠心病- pah的可操作性和了解其不可逆性。这些病理生物标志物的表达结合肺活检的病理变化可能对预测PAH的不可逆性具有重要价值。
Whether pulmonary arterial hypertension (PAH) is reversible in congenital heart disease (CHD) is important for the operability of CHD. However, little is known about that. Our research was aimed at exploring novel biomarkers and targets in the reversibility of CHD-PAH. CHD-PAH patients diagnosed with right heart catheterization (RHC) were enrolled (n = 14). Lung biopsy was performed during the repair surgery. After one year follow-up, mean pulmonary arterial pressures (mPAP) were evaluated by RHC to determine the diagnosis of reversible (mPAP < 25 mmHg, n = 10) and irreversible (mPAP ≥ 25 mmHg, n = 4) PAH. Harvested normal lung tissues (n = 6) were included as the control group. Pulmonary arteriole lesions were identified by pathological grading in tissue staining. iTRAQ-labelled mass-spectrometry analysis followed by immunohistochemistry and western blot was used to explore the most meaningful differential proteins. For enrolled patients, the histopathological grading of pulmonary vascular lesions in reversible CHD-PAH patients was all at grades 0–II while grades III–IV were shown only in irreversible CHD-PAH patients. Proteomic analysis identified 85 upregulated and 75 downregulated proteins, including cytoskeletal proteins and collagen chains, mainly involved in cell adhesion, extracellular matrix, cytoskeleton, immune response, and complement pathways. Among them, caveolin-1, filamin A expression, and cathepsin D combined with macrophagocytes counts were significantly increased; glutathione S-transferase mu1 (GSTM1) expression was significantly decreased in the irreversible CHD-PAH group (all P < 0.05). Caveolin-1, filamin A, and cathepsin D expression showed a positive relation and GSTM1 showed a negative relation with pathological grading. Upregulated caveolin-1, filamin A, and cathepsin D combined with increased macrophagocytes and downregulated GSTM1 may be potential biomarkers and targets in the irreversibility CHD-PAH, and which may be useful in evaluating the operability and understanding the irreversibility of CHD-PAH. Expression of these pathological biomarkers combined with pathological changes in lung biopsy may have great value in predicting the irreversibility of PAH.
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DOI：
10.1073/pnas.1320815111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Zheng, Xiaowei;Zhou, Alex-Xianghua;Poellinger, Lorenz
通讯作者：
Poellinger, Lorenz
DOI：
10.1161/hypertensionaha.109.139428
发表时间：
2009-12
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Yang Y;Parsons KK;Chi L;Malakauskas SM;Le TH
通讯作者：
Le TH
影响因子：
3.2
作者：
Huang, Jing;Wolk, John H.;Mathew, Rajamma
通讯作者：
Mathew, Rajamma
影响因子：
39.3
作者：
Manes, Alessandra;Palazzini, Massimiliano;Galie, Nazzareno
通讯作者：
Galie, Nazzareno
影响因子：
3.8
作者：
MISRA, P;SRIVASTAVA, SK;BOOR, PJ
通讯作者：
BOOR, PJ