Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis.
Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis.
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DOI：
10.3390/jcm9123974
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发表时间：
2020-12-08
影响因子：
3.9
通讯作者：
Sachdev U
中科院分区：
文献类型：
--
作者：
Cong G;Cui X;Ferrari R;Pipinos II;Casale GP;Chattopadhyay A;Sachdev U
大多数因外周动脉疾病 (PAD) 导致严重肢体缺血 (CLI) 的患者之前没有间歇性跛行 (IC)。我们假设转录组分析将识别 CLI 特异性途径，特别是在纤维化方面。 PAD 和非 PAD（对照）肌肉活检的衍生队列数据从基因表达综合库 (GSE120642) 获得。转录组分析表明，与非 PAD 对照 (N = 15) 和 IC (N = 20) 相比，CLI 患者 (N = 16) 具有独特的基因表达谱。对照组和 IC 之间有 98 个基因不同，CLI 和对照组之间有 2489 个基因不同，CLI 和 IC 患者之间有 2783 个基因不同。通路富集分析表明，与 TGFβ、胶原沉积和 VEGF 信号传导相关的通路在 CLI 中富集，但在 IC 中没有富集。九种纤维化核心基因表达的受试者工作曲线 (ROC) 分析显示，CLI 的 ROC 下面积 (AUC) 均 > 0.75。此外，验证队列中的纤维化面积（AUC = 0.81）和纤维化百分比（AUC = 0.87）验证了 IC 和对照（所有 n = 12）的纤维化区分 CLI。总之，转录组分析确定了纤维化途径（包括涉及 TGFβ 的途径）是 CLI 但不是 IC 的新基因表达特征。纤维化是 CLI 的一个重要特征，我们通过组织学证实了这一点，并且可能是 PAD 新疗法的目标。
Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD (controls) was obtained from the Gene Expression Omnibus (GSE120642). Transcriptomic analysis indicated CLI patients (N = 16) had a unique gene expression profile, when compared with non-PAD controls (N = 15) and IC (N = 20). Ninety-eight genes differed between controls and IC, 2489 genes differed between CLI and controls, and 2783 genes differed between CLI and IC patients. Pathway enrichment analysis showed that pathways associated with TGFβ, collagen deposition, and VEGF signaling were enriched in CLI but not IC. Receiver operating curve (ROC) analysis of nine fibrosis core gene expression revealed the areas under the ROC (AUC) were all >0.75 for CLI. Furthermore, the fibrosis area (AUC = 0.81) and % fibrosis (AUC = 0.87) in validation cohort validated the fibrosis discrimination CLI from IC and control (all n = 12). In conclusion, transcriptomic analysis identified fibrosis pathways, including those involving TGFβ, as a novel gene expression feature for CLI but not IC. Fibrosis is an important characteristic of CLI, which we confirmed histologically, and may be a target for novel therapies in PAD.
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影响因子：
17.1
作者：
Cummings BB;Marshall JL;Tukiainen T;Lek M;Donkervoort S;Foley AR;Bolduc V;Waddell LB;Sandaradura SA;O'Grady GL;Estrella E;Reddy HM;Zhao F;Weisburd B;Karczewski KJ;O'Donnell-Luria AH;Birnbaum D;Sarkozy A;Hu Y;Gonorazky H;Claeys K;Joshi H;Bournazos A;Oates EC;Ghaoui R;Davis MR;Laing NG;Topf A;Genotype-Tissue Expression Consortium;Kang PB;Beggs AH;North KN;Straub V;Dowling JJ;Muntoni F;Clarke NF;Cooper ST;Bönnemann CG;MacArthur DG
通讯作者：
MacArthur DG
DOI：
10.1007/978-1-0716-0223-2_4
发表时间：
2020-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Liu, Chia-Hsin;Di, Y Peter
通讯作者：
Di, Y Peter
影响因子：
2.4
作者：
Luo, Yanli;Huang, Lingjin;Hu, Qinghua
通讯作者：
Hu, Qinghua
影响因子：
16.1
作者：
Baues M;Dasgupta A;Ehling J;Prakash J;Boor P;Tacke F;Kiessling F;Lammers T
通讯作者：
Lammers T
影响因子：
3.7
作者：
Herráiz-Adillo Á;Martínez-Vizcaíno V;Cavero-Redondo I;Álvarez-Bueno C;Garrido-Miguel M;Notario-Pacheco B
通讯作者：
Notario-Pacheco B