Correlation of microvascular abnormalities and endothelial dysfunction in Type-1 Diabetes Mellitus (T1DM): A real-time intravital microscopy study

Correlation of microvascular abnormalities and endothelial dysfunction in Type-1 Diabetes Mellitus (T1DM): A real-time intravital microscopy study
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DOI:
10.3233/ch-2009-1199
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发表时间:
2009-01-01
影响因子:
2.1
通讯作者:
Devaraj, Sridevi
Devaraj, Sridevi
中科院分区:
医学4区
文献类型:
--
作者:
Cheung, Anthony T. W.;Tomic, M. Meighan (Smith);Devaraj, Sridevi

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我们假设实时体内微血管异常与T1 DM炎症/内皮功能障碍的生化标志物相关。利用计算机辅助活体显微镜对T1 DM和健康非糖尿病对照微循环进行实时量化。采用选定的生化标志物(高敏C反应蛋白(hsCRP)、可溶性血管细胞粘附分子(sVCAM)、可溶性细胞间粘附分子(sICAM)、可溶性E-选择素(sE-选择素)、硝基酪氨酸、超氧阴离子(O-2(-))、白细胞介素-1 β(IL-1 β)和肿瘤坏死因子-α(TNF-α))进行相关性分析。与对照组相比,T1 DM组微血管异常的严重程度(由算术严重程度指数(SI)反映)显著增加(5.89 +/- 1.47 vs. 2.34 +/- 1.48; P < 0.001)。此外,几种特定的微血管异常(与血流和形态测定相关)在T1 DM患者中显著更普遍。最后,炎症/内皮功能障碍标志物与特定微血管异常之间存在以下显著正相关性:sVCAM和异常血管直径(P = 0.004,OR = 1.033,OR的95%CI =(1.01,1.056)),超氧化物(O-2(-))释放和异常血管分布(P = 0.032,OR = 1.798,95%CI OR =(1.051,3.075)),sE-选择素与异常血管分布(P = 0.036,OR = 1.118,95%CI OR =(1.007,1.241))。鉴于这种显著的相关性,我们得出结论,这些特定的微血管异常可以作为内皮功能障碍的独特生理标志物,与疾病进展和治疗疗效研究中炎症/内皮功能障碍的生化标志物相关。
We hypothesize that real-time in vivo microvascular abnormalities should correlate with biochemical markers of inflammation/endothelial dysfunction in T1DM. Real-time quantification of T1DM and healthy non-diabetic control microcirculation was conducted utilizing computer-assisted intravital microscopy. Selected biochemical markers (high sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecules (sVCAM), soluble intercellular adhesion molecules (sICAM), soluble E-selectin (sE-selectin), nitrotyrosine, superoxide anion (O-2(-)), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)) were used for correlation. The severity of microvascular abnormalities, as reflected by the arithmetic severity index (SI), was significantly increased in T1DM vs. controls (5.89 +/- 1.47 vs. 2.34 +/- 1.48; P < 0.001). In addition several of the specific microvascular abnormalities (related to flow and morphometry) were significantly more prevalent in the T1DM patients. Finally, the following significant positive correlations existed between the inflammatory/endothelial dysfunction markers and specific microvascular abnormalities: sVCAM and abnormal vessel diameter (P = 0.004, OR = 1.033, 95% CI for OR = (1.01, 1.056)), superoxide (O-2(-)) release and abnormal vessel distribution (P = 0.032, OR = 1.798, 95% CI for OR = (1.051, 3.075)), and sE-selectin and abnormal vessel distribution (P = 0.036, OR = 1.118, 95% CI for OR = (1.007, 1.241)). In view of such significant correlations, we conclude that these specific microvascular abnormalities can serve as unique physiologic markers of endothelial dysfunction to correlate with the biochemical markers of inflammatory/endothelial dysfunction in disease progression and therapeutic efficacy studies.