Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis.
Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis.
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DOI：
10.1002/art.40193
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Varga J
中科院分区：
文献类型：
--
作者：
Korman BD;Marangoni RG;Hinchcliff M;Shah SJ;Carns M;Hoffmann A;Ramsey-Goldman R;Varga J
脂肪组织分泌脂肪因子、多肽，具有调节纤维化、炎症和血管稳态的有效作用。脂肪组织生物学和脂肪因子平衡失调最近与系统性硬化症（SSc）有关。我们试图确定循环脂肪因子水平的改变是否与SSc疾病亚群或临床表现相关。采用多重测定法测量了198例SSc患者和33例健康对照者的循环脂肪因子水平。血清脂肪因子水平与人口统计学和临床特征相关，包括肺动脉高压（PAH）。为了评估脂质素（一种参与补体途径激活的脂肪因子）在SSc中的相关性，我们分析了公开的遗传和转录组学数据。脂联素和脂素水平在对照组和患者之间有显著差异。Adipsin在局限性皮肤SSc患者中显著升高（OR 28.3, 95% C.I. 7.0-113.8, p<0.0001），其水平与血清自身抗体状态、肺功能和心血管参数以及PAH相关（OR 3.3, 95% C.I. 1.3-8.7, p=0.02）。脂素升高与PAH的相关性强于b型利钠肽（BNP）。此外，在SSc患者中，脂肪素基因单核苷酸多态性与PAH相关。转录组数据集分析显示，SSc-PAH患者中脂肪素表达升高。我们发现脂肪素是SSc中一种新的脂肪组织来源的多环芳烃标志物。循环脂肪素水平可能作为SSc的预测性生物标志物。在机制上，脂嘧啶可能代表了脂肪细胞功能障碍和补体通路激活之间的致病联系，并在SSc-PAH的发病机制中发挥重要作用。
Adipose tissues secrete adipokines, peptides with potent effects modulating fibrosis, inflammation, and vascular homeostasis. Dysregulated adipose tissue biology and adipokine balance have been recently implicated in systemic sclerosis (SSc). We sought to determine if altered circulating adipokine levels correlate with SSc disease subsets or clinical manifestations. Multiplex assays were used to measure circulating adipokine levels in 198 patients with SSc and 33 healthy controls. Serum adipokine levels were correlated with demographics and clinical features including pulmonary arterial hypertension (PAH). To assess the relevance of adipsin, an adipokine involved in complement pathway activation, in SSc, we analyzed publically available genetic and transcriptomic data. Levels of adiponectin and adipsin demonstrated significant differences between controls and patients. Adipsin was significantly elevated in patients with limited cutaneous SSc (OR 28.3, 95% C.I. 7.0-113.8, p<0.0001), and its levels were associated with serum autoantibody status, pulmonary function and cardiovascular parameters, and PAH (OR 3.3 95% C.I. 1.3-8.7, p=0.02). Elevated adipsin was more strongly associated with PAH than B-type natriuretic peptide (BNP). Moreover, in SSc patients, adipsin gene single nucleotide polymorphisms were associated with PAH. Transcriptome dataset analysis demonstrated elevated adipsin expression in patients with SSc-PAH. We identify adipsin as a novel adipose tissue-derived marker of PAH in SSc. Circulating adipsin levels might serve as predictive biomarkers in SSc. Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation, and play an important role in the pathogenesis of SSc-PAH.
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影响因子：
--
作者：
van den Hoogen, Frank;Khanna, Dinesh;Fransen, Jaap;Johnson, Sindhu R.;Baron, Murray;Tyndall, Alan;Matucci-Cerinic, Marco;Naden, Raymond P.;Medsger, Thomas A., Jr.;Carreira, Patricia E.;Riemekasten, Gabriela;Clements, Philip J.;Denton, Christopher P.;Distler, Oliver;Allanore, Yannick;Furst, Daniel E.;Gabrielli, Armando;Mayes, Maureen D.;van Laar, Jacob M.;Seibold, James R.;Czirjak, Laszlo;Steen, Virginia D.;Inanc, Murat;Kowal-Bielecka, Otylia;Mueller-Ladner, Ulf;Valentini, Gabriele;Veale, Douglas J.;Vonk, Madelon C.;Walker, Ulrich A.;Chung, Lorinda;Collier, David H.;Csuka, Mary Ellen;Fessler, Barri J.;Guiducci, Serena;Herrick, Ariane;Hsu, Vivien M.;Jimenez, Sergio;Kahaleh, Bashar;Merkel, Peter A.;Sierakowski, Stanislav;Silver, Richard M.;Simms, Robert W.;Varga, John;Pope, Janet E.
通讯作者：
Pope, Janet E.
影响因子：
6.5
作者：
Hill, Anita;Rother, Russell P.;Gladwin, Mark T.
通讯作者：
Gladwin, Mark T.
DOI：
10.1073/pnas.261428398
发表时间：
2001-12-04
影响因子：
11.1
作者：
Xu, YY;Ma, MH;Volanakis, JE
通讯作者：
Volanakis, JE
影响因子：
24.3
作者：
Mathai, S. C.;Bueso, M.;Hassoun, P. M.
通讯作者：
Hassoun, P. M.
影响因子：
--
作者：
SENALDI, G;LUPOLI, S;BLACK, CM
通讯作者：
BLACK, CM