title: Angiopoietin-like 4: A double-edged sword in atherosclerosis and ischemic stroke?
abstract: Ischemic stroke is one of the leading causes of death in the world, and thus is a major public health concern. Atherosclerosis, also known as atherogenesis, is a crucial risk factor for cerebral ischemia, yet how it develops remains largely unknown. It has been found, however, that angiopoietin-like protein 4 (ANGPTL4), a protein expressed in vascular endothelial cells, plays a role in the pathophysiology of atherosclerosis and may therefore be involved in ischemic stroke. ANGPTL4 activity is associated with endothelial cell integrity, inflammation, oxidative stress, and lipid metabolism. ANGPTL4 also serves as a potent inhibitor of the lipoprotein lipase, and may inhibit atherogenesis via regulating inflammatory signaling and lipid metabolism. In addition, ANGPTL4 plays a role in the regulation of oxidative stress. However, there currently exists a controversy on the role of ANGPTL4 in endothelial cells. Some studies indicate that ANGPTL4 can protect the integrity of endothelial cells, while others have shown that it can be destructive to the endothelium, thereby leading to the initiation of atherosclerosis. Thus, the effects of ANGPTL4 on development of atherosclerosis and thereby ischemic stroke, are undefined. Further research is needed to better understand ANGPTL4-mediated signaling pathways in endothelial function and to determine its potentials as therapeutic target for atherosclerosis and ischemic stroke.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People's Republic of China; Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Neuroscience Center, Department of Neurology, The First Norman Bethune Hospital of Jilin University, Changchun, People's Republic of China; Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA, USA.
authors.forename: Zhen-Ni
authors.initials: ZN
authors.lastname: Guo
authors.affiliation: Neuroscience Center, Department of Neurology, The First Norman Bethune Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Changhai Hospital, The First Affiliated Hospital of Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA, USA.
authors.forename: Sherrefa R
authors.initials: SR
authors.lastname: Burchell
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People's Republic of China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA, USA. Electronic address: johnzhang3910@yahoo.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000209:etiology; D050356:Lipid Metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D020521:Stroke / Q000209:etiology / Q000378:metabolism*
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins
keywords: Angiopoietin-like 4; Atherosclerosis; Endothelial cell; Inflammation; Ischemic stroke; Lipid metabolism; Oxidative stress