MOLECULAR MECHANISMS OF METHAMPHETAMINE-INDUCED CARDIOVASCULAR TOXICITY

• 作 者: XIE Weibing WANG Huijun
• 机 构: School of Forensic Medicine, Southern Medical University, Guangzhou, 510515
• 出 处: 第十四届全国药物依赖性学术会议暨国际精神疾病研讨会
• 发表日期: 2016年8期
• 关键词: methamphetamine cardiovascular toxicity Nupr1/CHOP/PUMA DDIT4-mTOR apoptosis

　　Methamphetamine (METH) abuse has been a serious global public health issue for decades.Previous studies have shown that METH causes detrimental effects on the nervous and cardiovascular systems.Cardiovascular complications are the second leading cause of death for METH abusers.It has been reported that METH exposure can cause extensive cardiac pathologies,including hypertension,aortic dissection,acute coronary syndromes,pulmonary arterial hypertension and METH-associated cardiomyopathy.An increasing number of clinical and autopsy reports also link METH use with angina,tachycardia,hypertension,myocarditis,dilated cardiomyopathy,arrhythmia,and sudden death.However,the mechanisms underlying METH-induced cardiovascular toxicity are largely unknown.Our recent research focuses on exploring the molecular mechanisms underlying METH-induced cardiovascular toxicity.In a series of recent studies,we have found that: 1) Nupr1/CHOP/PUMA pathway is essential for mitochondrion-related endothelial cell apoptosis induced by METH;2) DDIT4-mTOR axis can mediate METH-induced autophagy and apoptosis in cardiomyocytes;3) Chop-mediated endoplasmic reticulum stress-caused vascular smooth muscle cell apoptosis (VSMC) plays an essential role in METH-induced aortic dissection;and 4) C/EBPβalso plays an important role in METH-induced aortic dissection through activating the MMP9 activity.These findings not only shed light on METHs molecular mechanisms of cardiovascular toxicity,but also provide potential therapeutic targets for METH intoxication.