Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome. Human arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)). We first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients. Our results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

中文翻译：

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患有和未患有 2 型糖尿病的个体的各种动脉床中的基底膜蛋白：蛋白质组研究

基底膜 (BM) 积累是糖尿病 (DM) 中微血管疾病的标志。我们之前通过质谱法报道了来自 2 型 DM (T2DM) 患者的胸内动脉 (ITA) 中 BM 成分的显着上调。在这里，我们首先试图确定 BM 积累是否是 T2DM 不同动脉的共同特征，其次，确定 T2DM 对动脉蛋白质组的其他影响。通过液相色谱结合串联质谱 (LC-MS/MS) 分析在心脏和血管手术期间从特征良好的患者收集并储存在欧登塞动脉生物库中的人体动脉样本。我们包括升胸主动脉（ATA）（n = 10（2 型 DM，T2DM）和 n = 10（非 DM））；激光从颈动脉斑块中捕获显微解剖的斑块和培养基隔室（n = 10（T2DM）和 n = 9（非 DM））；以及来自 ITA 的培养基和外膜隔室（n = 9（T2DM）和 n = 7（非 DM））。我们首先扩展了我们之前对 T2DM 患者动脉中 BM 积累的发现，因为 12 种预定义的 BM 蛋白中有 7 种在由 > 90% 培养基组成的散装 ATA 中显着上调。虽然不太明显，但 BM 成分往往在 T2DM 患者的 ITA 介质中上调，但在邻近的外膜中没有。总体而言，我们没有检测到对颈动脉斑块或斑块相关介质中 BM 蛋白的影响。相反，补体因子、RNA 结合蛋白和纤维蛋白原似乎在 T2DM 患者的这些组织中受到调节。我们的研究结果表明，BM 蛋白的积累是 T2DM 患者非动脉粥样硬化动脉内侧层的普遍现象。此外，我们确定了对动脉蛋白质组的额外 T2DM 相关影响，这需要在未来的研究中进行验证。