Since its first description in 1982, the zoonotic life-threatening Shiga toxin-producing Escherichia coli O157:H7 has emerged as an important food- and water-borne pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome in humans. In the last decade, increases in E. coli O157:H7 outbreaks were associated with environmental contamination in water and through fresh produce such as green leaves or vegetables. Both intrinsic (genetic adaptation) and extrinsic factors may contribute and help E. coli O157:H7 to survive in adverse environments. This makes it even more difficult to detect and monitor food and water safety for public health surveillance. E. coli O157:H7 has evolved in behaviors and strategies to persist in the environment.

Our results suggest that the deletion of AT2 receptor reduced SHP-1 activity and restored VEGF actions, leading to an increased blood flow reperfusion after ischemia in diabetes mellitus.

Peripheral artery disease is a severe complication of diabetes. We have reported that the deletion of angiotensin type 2 receptor in diabetic mice promoted vascular angiogenesis in the ischaemic muscle 4 weeks following ischaemia. However, the angiotensin type 2 receptor deletion beneficial effects occurred 2 weeks post surgery suggesting that angiotensin type 2 receptor may regulate other pro-angiogenic signalling pathways during the early phases of ischaemia. Nondiabetic and diabetic angiotensin type 2 receptor–deficient mice ( Agtr2−/Y) underwent femoral artery ligation after 2 months of diabetes. Blood perfusion was measured every week up to 2 weeks post surgery. Expression of vascular endothelial growth factor, vascular endothelial growth factor receptor and endothelial nitric oxide synthase expression and activity were evaluated. Blood flow reperfusion in the ischaemic muscle of diabetic Agtr2+/Y mice was recovered at 35% as compared to a 68% recovery in diabetic Agtr2−/Y mice. The expression of vascular endothelial growth factor and its receptors was diminished in diabetic Agtr2+/Y mice, an observation not seen in diabetic Agtr2−/Y mice. Interestingly, Agtr2−/Y mice were protected from diabetes-induced glutathionylation, nitration and decreased endothelial nitric oxide synthase expression, which correlated with reduced endothelial cell death and enhanced vascular density in diabetic ischaemic muscle. In conclusion, our results suggest that the deletion of angiotensin type 2 receptor promotes blood flow reperfusion in diabetes by favouring endothelial cell survival and function.

Introduction: Ischemia due to narrowing of femoral artery and distal vessels is also a major cause of peripheral arterial disease and morbidity affecting patients with diabetes. We have previously reported that the inhibition of the angiogenic response to PDGF and VEGF in diabetic mice (DM) is associated with the increase expression of SHP-1, a protein that can be activated by the AT2 receptors. It has been shown that the deletion of AT2 receptor in mice promotes angiogenesis within the ischemic muscle, but its role in diabetic condition remains unknown. Hypothesis: Our hypothesis is that AT2 receptor induced SHP-1 which contributed to inhibition of pro-angiogenic factor actions in DM mice during ischemia. Methods: Non-DM and DM AT2 null mice underwent femoral artery ligation after two months of diabetes. Blood perfusion was measured every week up to 4 weeks post-surgery. Expression of AT1, AT2, angiotensin-converting enzymes (ACE1/2), SHP-1 and angiogenic factors was evaluated. Results: Blood flow in the ischemic muscle of DM-AT2KO mice recovered faster and up to 80% four weeks following the surgery, compared to a 51% recovery in DM mice. After four weeks, the expression of pro-angiogenic factors (HIF-1α and VEGF) was diminished in the DM and remained at a basal state in the DM-AT2KO suggesting a faster recovery process in these mice. Interestingly, two weeks after ligation, the expression of VEGF and HIF-1α are elevated in DM-AT2DM compared to DM mice and correlated with a reduction of SHP-1 expression in the ischemic muscles. Conclusion: Our results suggest that the deletion of AT2 receptor prevented SHP-1 expression induced by diabetes and restored pro-angiogenic factors causing blood flow reperfusion following ischemia.