Long-Term Type 1 Diabetes Enhances In-Stent Restenosis after Aortic Stenting in Diabetes-Prone BB Rats

Geanina Onuta,Bart J G L De Smet,Flip A Klatter,Jan-Luuk Hillebrands,Maaike Goris,Anton J M Roks,Mark Walther Boer,Harry Van Goor,Jan Rozing,Hendrik C Groenewegen

doi:10.1155/2011/396734

Abstract

Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months) spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6-7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA1c levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities.

Highlights

In-stent restenosis (ISR) is the most common complication associated with coronary stenting and is histologically characterized by occlusive neointima formation
Median age of diabetes onset in the BBDP rats (n = 7) that were stented and included for histological analysis was 82 days (Table 1)
Our results clearly demonstrated that longterm Diabetes mellitus (DM) significantly enhanced the development of ISR by 32% compared with non-DM age-matched thymectomized BBDP rats

Summary

Introduction

In-stent restenosis (ISR) is the most common complication associated with coronary stenting and is histologically characterized by occlusive neointima formation. DM is a risk factor for ISR development after using both drug-eluting and bare metal stents as revealed by various meta-analyses (primarily including type 2 diabetic patients) [15,16,17]. The beneficial effects on ISR of drug-eluting stents over bare metal stents as observed in non-diabetic patients appear to be less clear in diabetic patients. The exact pathogenetic mechanism underlying increased ISR development in diabetic patients is as yet unknown, it at least appears to be due to an exaggerated neointimal response after coronary stent placement as determined by intravascular ultrasound [18].

Methods

Results

Conclusion