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

Article type: Research Article

Authors: Cheung, Anthony T.W.^; | (Smith) Tomic, M. Meighan | Chen, Peter C.Y. | Miguelino, Eric | Li, Chin-Shang | Devaraj, Sridevi

Affiliations: Department of Pathology and Laboratory Medicine, University of California – Davis, School of Medicine, Sacramento, CA, USA | Shiley Center for Orthopedic Research and Education (SCORE), Scripps Clinic, and Department of Bioengineering, University of California – San Diego, La Jolla, CA, USA | Division of Biostatistics, Department of Public Health Sciences, University of California – Davis, Davis, CA, USA

Note: [] Corresponding author: Dr. Anthony Tze-Wai Cheung, Research-III Building, Suite 3400, University of California – Davis, Medical Center, 4645 Second Avenue, Sacramento, CA 95817, USA. Tel.: +1 916 734 3855; Fax: +1 916 734 2698; E-mail: [email protected].

Abstract: 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-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) 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.

Keywords: Computer-assisted intravital microscopy, T1DM, biochemical markers, physiologic markers, microvascular abnormalities

DOI: 10.3233/CH-2009-1199

Journal: Clinical Hemorheology and Microcirculation, vol. 42, no. 4, pp. 285-295, 2009