Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes.,PLOS ONE

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Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-01-23 , DOI: 10.1371/journal.pone.0227889
Moritz Lindquist Liljeqvist ₁ , Linnea Eriksson ₁ , Christina Villard ₁ , Mariette Lengquist ₁ , Malin Kronqvist ₁ , Rebecka Hultgren _{1,

2} , Joy Roy _{1,

2}

Affiliation

BACKGROUND Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease, and until today there is no other treatment available than surgical intervention. Dipeptidyl peptidase-4 (DPP4)-inhibitors, used clinically to treat type 2 diabetes, have in murine models been shown to attenuate aneurysm formation and decrease aortic wall matrix degradation, inflammation and apoptosis. Our aim was to investigate if DPP4 is present, active and differentially expressed in human AAA. METHODS AND RESULTS DPP4 gene expression was elevated in both media and adventitia of AAA tissue compared with control tissue, as measured by microarrays and qPCR, with consistent findings in external data. The plasma activity of DPP4 was however lower in male patients with AAA compared with age- and gender-matched controls, independently of comorbidity or medication. Immunohistochemical double staining revealed co-localization of DPP4 with cells positive for CD68, CD4 and -8, CD20, and SMA. Gene set enrichment analysis demonstrated that expression of DPP4 in AAA tissue correlated with expression of biological processes related to B- and T-cells, extracellular matrix turnover, peptidase activity, oxidative stress and angiogenesis whereas it correlated negatively with muscle-/actin-related processes. CONCLUSION DPP4 is upregulated in both media and adventitia of human AAA and correlates with aneurysm pathophysiological processes. These results support previous murine mechanistic studies and implicate DPP4 as a target in AAA disease.

中文翻译：

二肽基肽酶-4在腹主动脉瘤血管壁中增加并且与动脉瘤疾病过程相关。

背景技术腹主动脉瘤（AAA）是一种潜在的威胁生命的疾病，直到今天，除外科手术外，没有其他可用的治疗方法。临床上用于治疗2型糖尿病的二肽基肽酶4（DPP4）抑制剂已在鼠模型中显示出可减轻动脉瘤的形成并减少主动脉壁基质的降解，炎症和细胞凋亡。我们的目的是研究DPP4是否在人AAA中存在，活性和差异表达。方法和结果通过芯片和qPCR检测，与对照组织相比，AAA组织的中膜和外膜中DPP4基因的表达均升高，在外部数据中具有一致的发现。然而，与年龄和性别匹配的对照组相比，AAA男性患者的DPP4血浆活性较低，而与合并症或药物治疗无关。免疫组织化学双重染色显示DPP4与CD68，CD4和-8，CD20和SMA阳性细胞共定位。基因集富集分析表明，DPP4在AAA组织中的表达与与B细胞和T细胞，细胞外基质更新，肽酶活性，氧化应激和血管生成有关的生物学过程的表达相关，而与肌肉/肌动蛋白相关的过程呈负相关。。结论DPP4在人AAA的介质和外膜中均上调，并与动脉瘤的病理生理过程有关。这些结果支持以前的小鼠机制研究，并暗示DPP4是AAA疾病的靶标。基因集富集分析表明，DPP4在AAA组织中的表达与与B细胞和T细胞，细胞外基质更新，肽酶活性，氧化应激和血管生成有关的生物学过程的表达相关，而与肌肉/肌动蛋白相关的过程呈负相关。。结论DPP4在人AAA的介质和外膜中均上调，并与动脉瘤的病理生理过程有关。这些结果支持以前的小鼠机制研究，并暗示DPP4作为AAA疾病的靶标。基因集富集分析表明，DPP4在AAA组织中的表达与与B细胞和T细胞，细胞外基质更新，肽酶活性，氧化应激和血管生成有关的生物学过程的表达相关，而与肌肉/肌动蛋白相关的过程呈负相关。。结论DPP4在人AAA的介质和外膜中均上调，并与动脉瘤的病理生理过程有关。这些结果支持以前的小鼠机制研究，并暗示DPP4是AAA疾病的靶标。结论DPP4在人AAA的介质和外膜中均上调，并与动脉瘤的病理生理过程有关。这些结果支持以前的小鼠机制研究，并暗示DPP4是AAA疾病的靶标。结论DPP4在人AAA的介质和外膜中均上调，并与动脉瘤的病理生理过程有关。这些结果支持以前的小鼠机制研究，并暗示DPP4是AAA疾病的靶标。

更新日期：2020-01-24

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