Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension.
Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension.
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DOI：
10.1172/jci.insight.159578
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发表时间：
2022-09-22
期刊：
影响因子：
8
通讯作者：
Zhou, Yang
中科院分区：
文献类型：
--
作者：
Sun, Xiuna;Nakajima, Erika;Norbrun, Carmelissa;Sorkhdini, Parand;Yang, Alina Xiaoyu;Yang, Dongqin;Ventetuolo, Corey E.;Braza, Julie;Vang, Alexander;Aliotta, Jason;Banerjee, Debasree;Pereira, Mandy;Baird, Grayson;Lu, Qing;Harrington, Elizabeth O.;Rounds, Sharon;Lee, Chun Geun;Yao, Hongwei;Choudhary, Gaurav;Klinger, James R.;Zhou, Yang
几丁质酶 3 样 1 (CHI3L1) 是原型几丁质酶样蛋白，介导炎症、细胞增殖和组织重塑。有限的数据表明 CHI3L1 在人类肺动脉高压 (PAH) 中升高，并且与疾病严重程度相关。尽管 CHI3L1 作为损伤/修复反应的调节剂很重要，但其与肺血管重塑之间的关系尚不清楚。我们假设 CHI3L1 及其信号通路有助于肺动脉高压 (PH) 中发生的血管重塑反应。我们检查了各种形式PH患者（包括1组PAH和3组PH）血浆CHI3L1水平与PH严重程度的关系，发现血清CHI3L1的循环水平与较差的血流动力学相关，并与平均肺动脉压和肺血管阻力直接相关。我们还使用了 CHI3L1 组成型敲除和诱导性过度表达的转基因小鼠来检查其在缺氧、野百合碱和博莱霉素诱导的肺血管疾病模型中的作用。在所有 3 种肺血管疾病小鼠模型中，CHI3L1 缺失小鼠的肺动脉高压反应减轻，而过表达 CHI3L1 的转基因小鼠肺动脉高压反应增强。最后，单独使用CHI3L1足以诱导肺动脉平滑肌细胞增殖，抑制肺血管内皮细胞凋亡，诱导内皮屏障功能丧失，并诱导内皮-间质转化。这些发现表明，CHI3L1 及其受体在肺血管疾病病理学中发挥着不可或缺的作用，并可能为治疗与纤维化肺病相关的 PAH 和 PH 提供靶点。
Chitinase 3 like 1 (CHI3L1) is the prototypic chitinase-like protein mediating inflammation, cell proliferation, and tissue remodeling. Limited data suggest CHI3L1 is elevated in human pulmonary arterial hypertension (PAH) and is associated with disease severity. Despite its importance as a regulator of injury/repair responses, the relationship between CHI3L1 and pulmonary vascular remodeling is not well understood. We hypothesize that CHI3L1 and its signaling pathways contribute to the vascular remodeling responses that occur in pulmonary hypertension (PH). We examined the relationship of plasma CHI3L1 levels and severity of PH in patients with various forms of PH, including group 1 PAH and group 3 PH, and found that circulating levels of serum CHI3L1 were associated with worse hemodynamics and correlated directly with mean pulmonary artery pressure and pulmonary vascular resistance. We also used transgenic mice with constitutive knockout and inducible overexpression of CHI3L1 to examine its role in hypoxia-, monocrotaline-, and bleomycin-induced models of pulmonary vascular disease. In all 3 mouse models of pulmonary vascular disease, pulmonary hypertensive responses were mitigated in CHI3L1-null mice and accentuated in transgenic mice that overexpress CHI3L1. Finally, CHI3L1 alone was sufficient to induce pulmonary arterial smooth muscle cell proliferation, inhibit pulmonary vascular endothelial cell apoptosis, induce the loss of endothelial barrier function, and induce endothelial-mesenchymal transition. These findings demonstrate that CHI3L1 and its receptors play an integral role in pulmonary vascular disease pathobiology and may offer a target for the treatment of PAH and PH associated with fibrotic lung disease.
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较低的DHEA-S水平可以预测特发性，结缔组织疾病和先天性心脏病相关的肺动脉高压的绝经后妇女的疾病和恶化。
DOI：
10.1183/13993003.00467-2018
发表时间：
2018-06
期刊：
The European respiratory journal
影响因子：
--
作者：
Baird GL;Archer-Chicko C;Barr RG;Bluemke DA;Foderaro AE;Fritz JS;Hill NS;Kawut SM;Klinger JR;Lima JAC;Mullin CJ;Ouyang P;Palevsky HI;Palmisicano AJ;Pinder D;Preston IR;Roberts KE;Smith KA;Walsh T;Whittenhall M;Ventetuolo CE
通讯作者：
Ventetuolo CE
影响因子：
7.3
作者：
Baliga RS;Scotton CJ;Trinder SL;Chambers RC;MacAllister RJ;Hobbs AJ
通讯作者：
Hobbs AJ
影响因子：
7.3
作者：
Collum, Scott D.;Chen, Ning-Yuan;Karmouty-Quintana, Harry
通讯作者：
Karmouty-Quintana, Harry
影响因子：
10.8
作者：
Aliotta, Jason M.;Pereira, Mandy;Klinger, James R.
通讯作者：
Klinger, James R.
影响因子：
2.1
作者：
Hartopo, A. B.;Arfian, N.;Emoto, N.
通讯作者：
Emoto, N.