Role of endogenous angiogenesis inhibitors in Down syndrome.
New blood vessel growth via angiogenesis is a fundamental process in both physiological and pathological conditions. Physiological angiogenesis is critical during embryogenesis and placental development, whereas pathological angiogenesis plays an important role in the progression of many diseases, most notably tumor growth. Tumor angiogenesis is well accepted to be regulated by a balance of proangiogenic and antiangiogenic factors produced both by tumor cells and surrounding stromal cells. For many years, investigation of antiangiogenic therapies for cancer has focused on the proangiogenic cytokine, vascular endothelial growth factor; its receptors; or downstream signaling pathways. However, more recently with the identification of endogenous angiogenesis inhibitors, studies have turned toward understanding the role of endogenous antiangiogenic proteins in preventing disease progression. Clinical clues have suggested that specific populations may have dysregulated angiogenesis due to differential expression of endogenous angiogenesis regulators. For example, individuals with Down syndrome may possess a systemic antiangiogenic state with a significantly decreased incidence of angiogenesis-dependent diseases. Our work suggests that endogenous angiogenesis inhibitors may be the master regulators controlling progression of angiogenesis-dependent diseases such as vascular anomalies and cancer. The molecular regulation of angiogenesis is not yet fully understood; however, the Down syndrome population may give us insights toward novel therapies for controlling angiogenesis in disease.
Vascular Biology Program, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. sandra.ryeom@childrens.harvard.edu
Sandra
S
Ryeom
Judah
J
Folkman
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology; D000071097:ADAMTS1 Protein; D020533:Angiogenesis Inhibitors / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D043170:Collagen Type XVIII / Q000378:metabolism; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000235:genetics*; D043169:Endostatins / Q000235:genetics / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000503:physiopathology; D019700:Thrombospondin 1 / Q000235:genetics / Q000502:physiology; D054079:Vascular Malformations / Q000235:genetics
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D004268:DNA-Binding Proteins; D043169:Endostatins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D019700:Thrombospondin 1; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human