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.

Angiopoietin-Like Proteins in Angiogenesis, Inflammation and Cancer

“…It has been reported as pro- or anti-angiogenic protein and proposed to play a role as gatekeeper regulating vascular integrity and angiogenesis in a context-dependent manner. 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 [ 68 ].…”

Pentraxin-3, Angiopoietin-Like Protein-3, Angiopoietin-Like Protein-4 and Angiopoietin-Like Protein-8 Levels in Morbid Obese Children

“…In human clinical trials, antisense oligonucleotide and monoclonal antibodybased inactivation of ANGPTL3 for the treatment of dyslipidaemia and atherosclerosis are being investigated. Oligonucleotides targeting ANGPTL3 retarded the atherosclerosis progression and reduced atherogenic lipoprotein levels [23,27] .…”

Effect of Maxing Shigan Tang on H1N1 Influenza A Virus-Associated Acute Lung Injury in Mice

“…It was reported that ANGPTL4 participates in many inflammation responses, especially in lung inflammation and alveolar epithelial cell death, which could lead to ALI [24,25]. Whether it also plays an important role in H1N1-induced ALI remains unclear.…”