Complement Gene Expression is Upregulated in the Type 2 Diabetic Heart Following Myocardial Ischemia and Reperfusion

Abstract

There are several complications that contribute to the increased severity of ischemic heart disease in type 2 diabetes. Recent evidence suggests that activation of the complement component of innate immunity may contribute to the increased severity and mortality observed in the diabetic heart after ischemia/reperfusion (I/R). To further understand the role of complement gene expression in I/R injury, qRTPCR was performed on cardiac tissue samples taken from the at-risk region of Zucker Diabetic Fatty (ZDF) rats following 30 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Comparison of gene expression in myocardial I/R tissues from ischemic ZDF rats to non-ischemic ZDF demonstrates that complement component C3 gene expression was increased 1.6 fold. This finding parallels work from our laboratory demonstrating that there is significant complement component C3 deposition in the at-risk region of the ZDF heart compared to the Zucker Lean Control (ZLC) (ZLC: 44.3 ± 8.5%; ZDF: 82.4 ± 12.5%; p < 0.05). These results suggest that generation of complement within the myocardium may contribute to total complement content within the type 2 diabetic heart following I/R. The increased expression of C3 may play a role in the exacerbated inflammatory response to ischemia and reperfusion observed in the type 2 diabetic heart. Supported by NIH HLB 58859, AHA 0610018Z, and HHMI 52003749