Involvement of P2Y 12 receptor of stellate ganglion in diabetic cardiovascular autonomic neuropathy
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ORIGINAL ARTICLE
Involvement of P2Y12 receptor of stellate ganglion in diabetic cardiovascular autonomic neuropathy Jingjing Guo 1 & Xuan Sheng 1 & Yu Dan 1 & Yurong Xu 1 & Yuanruohan Zhang 2 & Huihong Ji 3 & Jiayue Wang 3 & Zixi Xu 3 & Hongyu Che 2 & Guodong Li 1,4 & Shangdong Liang 1 & Guilin Li 1 Received: 28 December 2017 / Accepted: 26 June 2018 # Springer Nature B.V. 2018
Abstract Diabetes as a chronic epidemic disease with obvious symptom of hyperglycemia is seriously affecting human health globally due to the diverse diabetic complications. Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of both type 1 and type 2 diabetes and incurs high morbidity and mortality. However, the underlying mechanism for DCAN is unclear. It is well known that purinergic signaling is involved in the regulation of cardiovascular function. In this study, we examined whether the P2Y12 receptor could mediate DCAN-induced sympathetic reflexes. Our results revealed that the abnormal changes of blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were improved in diabetic rats treated with P2Y12 short hairpin RNA (shRNA). Meanwhile, the expression of P2Y12 receptor, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and connexin 43 (Cx43) in stellate ganglia (SG) was decreased in P2Y12 shRNA-treated diabetic rats. In addition, knocking down the P2Y12 receptor also inhibited the activation of p38 MARK in the SG of diabetic rats. Taken together, these findings demonstrated that P2Y12 receptor in the SG may participate in developing diabetic autonomic neuropathy, suggesting that the P2Y12 receptor could be a potential therapeutic target for the treatment of DCAN. Keywords P2Y12 receptor . Diabetic cardiovascular autonomic neuropathy . Stellate ganglia . Satellite glial cells
Introduction Diabetes mellitus is mainly due to the defects of insulin secretion and/or insulin action, displaying chronic hyperglycemia accompanied by the disorders in carbohydrate, lipid, and protein metabolism [1]. The incidence of diabetes is fast increasing [2] and the number of patients with diabetes mellitus will rise from 415 million in 2015 to 642 million by 2040, according to the latest data from the International Diabetes Federation [3]. Diabetic cardiovascular autonomic neuropathy
* Guilin Li [email protected] 1
Department of Physiology, Medical College of Nanchang University, Nanchang 330006, China
2
Queen Mary School, Medical College of Nanchang University, Nanchang 330006, China
3
Department of the First Clinical, Medical College of Nanchang University, Nanchang 330006, China
4
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
(DCAN) is one of the most common complications in diabetic patients [4]. DCAN is defined as the impairment of autonomic control of the cardiovascular system in the case of diabetes after exclusion of other causes [5]. The clinical manifestations of DCAN include sinus tachycardia, exercise into
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