Parstatin, a novel protease-activated receptor 1-derived inhibitor of angiogenesis.
Angiogenesis, the process of forming new blood vessels, is a well established and clinically relevant feature of a variety of disease states. Whether blood vessels sprout in a given tissue environment depends on the balance between factors that stimulate angiogenesis and those that impede it. Potent pro-angiogenic factors such as vascular endothelial growth factor (VEGF) have been identified, validated, and successfully used in the clinic. Likewise, anti-angiogenic factors are also emerging as biologically relevant and therapeutically useful entities. PAR1 is a G protein-coupled receptor (GPCR) that participates in hemostasis and vascular development and that mediates the angiogenic activity of thrombin. PAR1 is activated through proteolytic cleavage of its first forty-one extracellular residues by a variety of proteases, most notably thrombin. However, little effort has focused on the forty-one-residue peptide fragment liberated during PAR1 activation. Tsopanoglou and colleagues have now demonstrated that this peptide, parstatin, has intriguing antiangiogenic activity, and, in a follow-up study, they demonstrate its potential pharmacological utility using a rat model of ischemic heart disease.
Duncan
Michael B
MB
Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. mduncan1@bidmc.harvard.edu
Kalluri
Raghu
R
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004358:Drug Therapy; D015870:Gene Expression; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; C535229:PAR-1 receptor (1-41), human; D010446:Peptide Fragments; D044463:Receptor, PAR-1