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Neuroendocrine Research in Health and Disease

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Front. Neurosci. | doi: 10.3389/fnins.2019.00454

Therapeutic Potential of Oxytocin in Atherosclerotic Cardiovascular Disease: Mechanisms and Signaling Pathways

 Hui Zhu1*,  Yu-Feng Wang1*,  Ping Wang1,  Stephani C. Wang2, Haipeng Yang1, Chunmei Lu1,  Shuwei Jia1, Xiaoyu Liu1,  Xiaoran Wang1, Dexin Meng3 and  Danian Qin4
  • 1Harbin Medical University, China
  • 2Albany Medical College, United States
  • 3Jiamusi University, China
  • 4Shantou University Medical College, China

Coronary artery disease (CAD) is a major cardiovascular disease responsible for high morbidity and mortality worldwide. The major pathophysiological basis of CAD is atherosclerosis in association with varieties of immunometabolic disorders that can suppress oxytocin (OT) receptor (OTR) signaling in the cardiovascular system (CVS). By contrast, OT not only maintains cardiovascular integrity but also has the potential to suppress and even reverse atherosclerotic alterations and CAD. These protective effects of OT are associated with its protection of the heart and blood vessels from immunometabolic injuries and the resultant inflammation and apoptosis through both peripheral and central approaches. As a result, OT can decelerate the progression of atherosclerosis and facilitate the recovery of CVS from these injuries. At the cellular level, the protective effect of OT on CVS involves a broad array of OTR signaling events. These signals mainly belong to the reperfusion injury salvage kinase pathway that is composed of phosphatidylinositol 3-kinase-Akt-endothelial nitric oxide synthase cascades and extracellular signal-regulated protein kinase 1/2. Additionally, AMP-activated protein kinase, Ca2+/calmodulin-dependent protein kinase signaling and many others are also implicated in OTR signaling in the CVS protection. These signaling events interact coordinately at many levels to suppress the production of inflammatory cytokines and the activation of apoptotic pathways. A particular target of these signal events is endoplasmic reticulum (ER) stress and mitochondrial oxidative stress that interact through mitochondria-associated ER membrane. In contrast to these protective effects and machineries, rare but serious cardiovascular disturbances were also reported in labor induction and animal studies including hypotension, reflexive tachycardia, coronary spasm or thrombosis and allergy. Here, we review our current understanding of the protective effect of OT against varieties of atherosclerotic etiologies as well as the approaches and underlying mechanisms of these effects. Moreover, cardiovascular disturbances following OT application are also discussed to avoid unwanted effects in clinical trials of OT usages.

Keywords: Atherosclerosis, Coronary Artery Disease, etiology, Oxytocin, Signaling Pathways

Received: 14 Dec 2018; Accepted: 23 Apr 2019.

Edited by:

Pierrette Gaudreau, Université de Montréal, Canada

Reviewed by:

Marta Busnelli, Italian National Research Council (CNR), Italy
Philip M. McCabe, University of Miami, United States  

Copyright: © 2019 Zhu, Wang, Wang, Wang, Yang, Lu, Jia, Liu, Wang, Meng and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Hui Zhu, Harbin Medical University, Harbin, China, dzhuhui@aliyun.com
Dr. Yu-Feng Wang, Harbin Medical University, Harbin, China, yufengwang@ems.hrbmu.edu.cn