OBJECTIVE: C-reactive protein (CRP) levels in diabetes predict cardiovascular events. Also, human CRP (hCRP) exacerbated the proinflammatory, pro-oxidant and procoagulant states in a spontaneous model of type 1 diabetes mellitus (T1DM), the biobreeding (BB) rat. Since there is a paucity of data examining the role of CRP on endothelial dysfunction in animal models of diabetes, we tested this hypothesis in the diabetic BB rat. METHODS: Diabetic BB rats (n = 4 per group) were injected with human serum albumin (HSA) or hCRP [hCRP = 20 mg/kg body weight; intraperitoneal (IP)] for three consecutive days. The rats were euthanized on day 4. Biomarkers that were assayed included endothelin-1 (ET-1), soluble intracellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (vWF) and 6-keto prostaglandin F1-alpha (6-keto PGF1-α) in plasma. RESULTS: hCRP administration resulted in a significant increase in plasma levels. Furthermore, hCRP-treated rats had significantly increased circulating levels of ET-1 (1.12 ± 0.6 pg/mL versus 0.4 ± 0.21 pg/mL), vWF (45 ± 2.4 ng/mL versus 34 ± 7 ng/mL) and sICAM-1 (41 ± 3 ng/mL versus 34 ± 3.4 ng/mL) compared to HSA-treated rats (p < 0.05). There was no significant effect on 6-keto PGF1-α levels. CONCLUSION: Hence, in this preliminary report, we make the novel observation that hCRP induces endothelial dysfunction in a spontaneous model of T1DM, and this could have implications for the vascular complications in diabetics.
OBJECTIVE:C-reactive protein (CRP) levels in diabetes predict cardiovascular events. Also, humanCRP (hCRP) exacerbated the proinflammatory, pro-oxidant and procoagulant states in a spontaneous model of type 1 diabetes mellitus (T1DM), the biobreeding (BB) rat. Since there is a paucity of data examining the role of CRP on endothelial dysfunction in animal models of diabetes, we tested this hypothesis in the diabetic BB rat. METHODS:Diabetic BB rats (n = 4 per group) were injected with human serum albumin (HSA) or hCRP [hCRP = 20 mg/kg body weight; intraperitoneal (IP)] for three consecutive days. The rats were euthanized on day 4. Biomarkers that were assayed included endothelin-1 (ET-1), soluble intracellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (vWF) and 6-keto prostaglandin F1-alpha (6-keto PGF1-α) in plasma. RESULTS:hCRP administration resulted in a significant increase in plasma levels. Furthermore, hCRP-treated rats had significantly increased circulating levels of ET-1 (1.12 ± 0.6 pg/mL versus 0.4 ± 0.21 pg/mL), vWF (45 ± 2.4 ng/mL versus 34 ± 7 ng/mL) and sICAM-1 (41 ± 3 ng/mL versus 34 ± 3.4 ng/mL) compared to HSA-treated rats (p < 0.05). There was no significant effect on 6-keto PGF1-α levels. CONCLUSION: Hence, in this preliminary report, we make the novel observation that hCRP induces endothelial dysfunction in a spontaneous model of T1DM, and this could have implications for the vascular complications in diabetics.
Entities:
Keywords:
C-reactive protein; endothelial dysfunction; inflammation; type 1 diabetes mellitus
Authors: Tianteng Fan; Shona C Fang; Jennifer M Cavallari; Ian J Barnett; Zhaoxi Wang; Li Su; Hyang-Min Byun; Xihong Lin; Andrea A Baccarelli; David C Christiani Journal: BMC Public Health Date: 2014-12-16 Impact factor: 3.295