Cheung Anthony T W, Tomic M Meighan Smith, Chen Peter C Y, Miguelino Eric, Li Chin-Shang, Devaraj Sridevi
Department of Pathology and Laboratory Medicine, University of California - Davis, School of Medicine, Sacramento, CA 95817, USA.
Clin Hemorheol Microcirc. 2009;42(4):285-95. doi: 10.3233/CH-2009-1199.
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 (O2-), interleukin-1beta (IL-1beta) 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 (O2-) 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.
我们推测，1型糖尿病患者体内实时微血管异常应与炎症/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1型糖尿病患者和健康非糖尿病对照者的微循环进行实时定量分析。选取了一些生化标志物（高敏C反应蛋白（hsCRP）、可溶性血管细胞黏附分子（sVCAM）、可溶性细胞间黏附分子（sICAM）、可溶性E选择素（sE选择素）、硝基酪氨酸、超氧阴离子（O2-）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α））进行相关性分析。与对照组相比，1型糖尿病患者微血管异常的严重程度（通过算术严重指数（SI）反映）显著增加（5.89±1.47对2.34±1.48；P<0.001）。此外，1型糖尿病患者中一些特定的微血管异常（与血流和形态测量有关）更为普遍。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：sVCAM与血管直径异常（P=0.004，OR =1.033，OR的95%可信区间=（1.01，1.056））、超氧阴离子（O2-）释放与血管分布异常（P=0.032，OR =1.798，OR的95%可信区间=（1.051，3.075））以及sE选择素与血管分布异常（P=0.036，OR =1.118，OR的95%可信区间=（1.007，1.241））。鉴于这些显著的相关性，我们得出结论，这些特定的微血管异常可作为内皮功能障碍的独特生理标志物，在疾病进展和治疗疗效研究中与炎症/内皮功能障碍的生化标志物相关联。
