In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 94, No. 6 ( 2009-06-01), p. 2171-2177
Abstract:
Context: Macular edema contributes to visual impairment, and albuminuria is associated with increased cardiovascular mortality in adults with type 2 diabetes mellitus. These microvascular complications result from increased capillary leakage of plasma proteins whose causation is not completely understood. Objective: The objective of the present study was to test whether plasma from type 2 diabetes with maculopathy/albuminuria or control subjects contains autoantibodies that can induce apoptosis or activate Rho kinase (ROCK) in endothelial cells. Design: A cohort of Veterans Affairs Diabetes Trial adults ( & gt;40 yr of age) was randomized to standard vs. intensive glycemic treatment lasting 5–7.5 yr. Setting: The study was conducted in outpatient clinics. Patients: Case and age-matched control subjects who differed for the baseline presence of significant diabetic maculopathy and/or progression to macro-albuminuria were included in the study. Intervention: Pharmacological and lifestyle interventions in the Veterans Affairs Diabetes Trial generally resulted in substantially improved glycemic, blood pressure, and lipid levels. Results: Autoantibodies from patients with macular edema or progression to albuminuria potently induced caspase-dependent apoptosis in endothelial cells (up to 60%), whereas IgG from age-matched normal plasma caused much less apoptosis ( & lt;10%; P & lt; 0.0001). The active inhibitory autoantibodies triggered stress fiber formation in endothelial cells likely through the activation of Rho guanosine 5′-triphosphatase, which could be nearly completed inhibited by 10 μm Y27632, a specific ROCK inhibitor. Conclusions: These results suggest that autoantibodies from a subset of advanced type 2 diabetes may contribute to diabetic vascular complications by activating ROCK, inducing stress fiber formation and apoptosis in endothelial cells.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jc.2008-2354
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2009
detail.hit.zdb_id:
2026217-6
Permalink