Correlation of microvascular abnormalities and endothelial dysfunction in Type-1 Diabetes Mellitus (T1DM): a real-time intravital microscopy study.
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.
Cheung
Anthony T W
AT
Department of Pathology and Laboratory Medicine, University of California - Davis, School of Medicine, Sacramento, CA 95817, USA. anthony.cheung@ucdmc.ucdavis.edu
Tomic
M Meighan Smith
MM
Chen
Peter C Y
PC
Miguelino
Eric
E
Li
Chin-Shang
CS
Devaraj
Sridevi
S
D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis; D008297:Male; D018715:Microscopy, Video / Q000379:methods*; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D013481:Superoxides / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D002097:C-Reactive Protein