title: Small GTP-binding proteins and mitogen-activated protein kinases as promising therapeutic targets of vascular remodeling.
abstract: OBJECTIVE
  To summarize the most recent findings concerning the targeting of mitogen-activated protein kinases and small GTP-binding proteins toward vascular remodeling together with molecular mechanisms of their activations in vascular pathophysiology.
  
  
  RESULTS
  In addition to targeting the classical Ras/extracellular signal-regulated kinase cascade, Rho-kinase inhibitors, as well as the HMG-CoA reductase inhibitors, or 'statins', have pleiotropic efficacy for experimental cardiovascular diseases that involve inhibition of the signal transduction cascades originated by the small GTP-binding proteins such as Rho and Rac. Moreover, the underlying molecular mechanisms of the activation of these small GTP-binding proteins and downstream mitogen-activated protein kinases in cardiovascular tissue and cells have recently been better characterized. Additionally, gene-targeting studies in animal models are revealing select roles of the isoforms of these signaling proteins in the pathophysiology of cardiovascular disease. This is exemplified by the role of c-Jun NH(2)-terminal kinases in mediating atherosclerosis and diabetes.
  
  
  CONCLUSIONS
  Characterization of the function of small GTP-binding proteins, mitogen-activated protein kinases and their effectors in cardiovascular pathophysiology can be readily identified by using select inhibitors, dominant-negative gene transfer and the generation of select gene-targeted animals. These findings strongly support the notion that small GTP-binding proteins and mitogen-activated protein kinases are promising therapeutic targets toward cardiovascular diseases.
authors.affiliation: Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Heigoro
authors.initials: H
authors.lastname: Shirai
authors.forename: Michael
authors.initials: M
authors.lastname: Autieri
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014652:Vascular Diseases / Q000503:physiopathology* / Q000628:therapy; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins