Angiopoietin-like proteins--potential therapeutic targets for metabolic syndrome and cardiovascular disease.
Recent major increases in obesity and related metabolic diseases (known as the metabolic syndrome (MetS)) because of sedentary lifestyles and overnutrition in developed and developing countries, are an exploding medical and social problem. These conditions are associated with increased risk of cardiovascular disease (CVD), the leading cause of death. Thus, it is necessary to understand the molecular basis underlying MetS and develop effective preventive and therapeutic approaches against CVD. To date, 7 angiopoietin-like proteins (Angptls) that are structurally similar to angiopoietins have been identified. However, none binds to the angiopoietin receptor, Tie2, or to the closely related Tie1 receptor, suggesting that these ligands function differently from angiopoietins. Some Angptls potently regulate angiogenesis, similar to angiopoietins, whereas others have pleiotropic activity other than angiogenesis and function in lipid and energy metabolism. In this review, we focus on the roles of Angptl2 and Angptl6/angiopoietin-like growth factor (AGF) in the development of MetS and CVD, and discuss the potential for Angptl2 and Angptl6/AGF to function as molecular targets for the prevention and treatment of both conditions.
Oike
Yuichi
Y
Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. oike@gpo.kumamoto-u.ac.jp
Tabata
Mitsuhisa
M
D043924:Angiogenesis Modulating Agents / Q000627:therapeutic use; D000091302:Angiopoietin-Like Protein 2; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000737:chemistry / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
C485792:ANGPTL2 protein, human; C477601:ANGPTL6 protein, human; D043924:Angiogenesis Modulating Agents; D000091302:Angiopoietin-Like Protein 2; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D002317:Cardiovascular Agents; D000960:Hypolipidemic Agents