The Role of Angiopoietin-Like Proteins in Angiogenesis and Metabolism

Hato, Tai; Tabata, Mitsuhisa; Oike, Yuichi

doi:10.1016/j.tcm.2007.10.003

« Previous Next »Trends in Cardiovascular Medicine
Volume 18, Issue 1 , Pages 6-14, January 2008

The Role of Angiopoietin-Like Proteins in Angiogenesis and Metabolism

Tai Hato
- Laboratory of Vascular Biology and Metabolism, Center for Integrated Medical Research, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of General Thoracic Surgery, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan
Mitsuhisa Tabata
- Laboratory of Vascular Biology and Metabolism, Center for Integrated Medical Research, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of Internal Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
Yuichi Oike
- Laboratory of Vascular Biology and Metabolism, Center for Integrated Medical Research, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
- PRESTO, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
- Address correspondence to: Yuichi Oike, MD, PhD, Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan. Tel.: (+81) 96 373 5140; fax: (+81) 96 373 5145

Recently, a family of proteins structurally similar to the angiogenic regulating factors angiopoietins was identified and designated “angiopoietin-like proteins” (Angptls). Encoded by seven genes, Angptls 1 to 7 all possess an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain, both characteristic of angiopoietins. However, Angptls do not bind to either the angiopoietin receptor Tie2 or the related protein Tie1 and remain orphan ligands. Nonetheless, Angptls 1, 2, 3, 4, and Angptl6/angiopoietin-related growth factor function to regulate angiogenesis. Angptls 3, 4, and Angptl6/angiopoietin-related growth factor also appear to directly regulate lipid, glucose, and energy metabolism independently of angiogenic effects. Recently, several lines of evidence reveal differential roles of Angptl structural domains in both angiogenesis and metabolism. Here, we briefly review what is currently known about Angptls function.