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Autoimmune-mediated vascular injury occurs prior to sustained hyperglycemia in a murine model of type I diabetes mellitus. J Surg Res 2011 Jun 15;168(2):e195-202

Date

04/08/2011

Pubmed ID

21470634

Pubmed Central ID

PMC3091976

DOI

10.1016/j.jss.2011.01.021

Scopus ID

2-s2.0-79955846147   2 Citations

Abstract

BACKGROUND: Accelerated cardiovascular disease in patients with type I diabetes (TID) is a well-described condition and serious clinical obstacle. At present, the notion that early atherogenesis is largely dependent on sustained hyperglycemia remains in question. We hypothesize that an alteration in T lymphocyte homeostasis may result in early vascular inflammation, which might amplify subsequent blood vessel injury in euglycemia.

METHODS: A murine model of carotid arterial ligation was employed to induce neointimal hyperplasia (NIH) in C57/Bl6 (non-autoimmune) and non-obese diabetic (NOD) mice. Additionally, adoptive transfer of NOD splenocytes into immunodeficient NOD mice (NOD.scid) was undertaken to evaluate the influence of restored autoimmunity on NIH development.

RESULTS: Interestingly, compared with C57/Bl6 mice, the NOD demonstrate a significant increase in neointimal area. Conversely, the NOD.scid mice (immunodeficient control) reveal almost no evidence of vascular injury. While evidence of early vascular inflammation can be detected in the injured NOD vasculature, uninjured contralateral vessels and those of the NOD.scid have minimal T cell infiltration. Following reconstitution of autoimmune responses via NOD splenocyte adoptive transfer, accelerated vascular pathology is restored.

CONCLUSIONS: These observations suggest that autoimmunity, in the setting of impending hyperglycemia, may contribute to accelerated vascular inflammation and subsequent pathology.

Author List

Zimmerman MA, Haskins K, Bradley B, Gilman J, Gamboni-Robertson F, Flores SC

Author

Michael A. Zimmerman MD, FACS Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adoptive Transfer
Animals
CD4 Lymphocyte Count
Carotid Artery Diseases
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1
Diabetic Angiopathies
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Neointima
Spleen
T-Lymphocytes
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0