Melatonin attenuates angiotensin II-induced abdominal aortic aneurysm through the down-regulation of matrix metalloproteinases

// Jing Kong 1,* , Ya Zhang 1,* , Shanshan Liu 1 , Hongxuan Li 1 , Shangming Liu 2 , Jingjing Wang 3 , Xiaoteng Qin 1 , Xiuxin Jiang 4 , Jianmin Yang 1 , Cheng Zhang 1 and Wencheng Zhang 1 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China 2 Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, China 3 Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, China 4 Department of General Surgery, Virtual Laboratory, Qilu Hospital of Shandong University, Jinan, China * These authors have contributted equally to this work Correspondence to: Wencheng Zhang, email: // Keywords : abdominal aortic aneurysm, melatonin, HuR, MMP2, MMP9, Pathology Section Received : December 16, 2016 Accepted : January 24, 2017 Published : February 04, 2017 Abstract Abdominal aortic aneurysm (AAA) affects more than 5% of the population in developed countries and the pharmacotherapies for AAA are limited. Here, we explored whether melatonin regulates the development of AAA. In smooth muscle cells, melatonin treatment decreases angiotensin II-induced matrix metalloproteinase 2 (MMP2) and MMP9 expression. Human antigen R (HuR) could bind with the adenylateuridylate-rich elements of MMP2 and MMP9 mRNAs 3′ untranslated region, resulting in the increased stability of MMP2 and MMP9 mRNAs. HuR is required for angiotensin II-induced MMP2 and MMP9 expression. Moreover, melatonin suppresses angiotensin II-induced HuR expression through inhibiting NF-κB signaling, leading to decreased MMP2 and MMP9 levels. Finally, melatonin attenuates the development of AAA in ApoE -/- mice infused with angiotensin II in vivo . These data support a role of HuR in the development of AAA and possible therapeutic roles for melatonin and/or HuR inhibition in AAA.