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

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-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.

• Authors: Anthony T W Cheung, M Meighan Smith Tomic, Peter C Y Chen, Eric Miguelino, Chin-Shang Li, Sridevi Devaraj
• Journal: Clinical hemorheology and microcirculation (Clin Hemorheol Microcirc) Vol. 42 Issue 4 Pg. 285-95 ( 2009) ISSN: 1875-8622 [Electronic] Netherlands
• PMID: 19628894 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cell Adhesion Molecules
• E-Selectin
• Interleukin-1beta
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Superoxides
• C-Reactive Protein

Topics

• Adolescent
• Adult
• C-Reactive Protein (analysis)
• Cell Adhesion Molecules (blood)
• Diabetes Mellitus, Type 1 (physiopathology)
• E-Selectin (blood)
• Endothelium, Vascular (immunology, physiopathology)
• Female
• Humans
• Interleukin-1beta (analysis)
• Male
• Microscopy, Video (methods)
• Microvessels (pathology)
• Middle Aged
• Superoxides (analysis)
• Tumor Necrosis Factor-alpha (analysis)
• Vascular Cell Adhesion Molecule-1 (blood)
• Young Adult