The extracellular signal-regulated kinase (ERK) pathway: a potential therapeutic target in hypertension

Article, Review English OPEN
Roberts, Richard E. (2012)
  • Publisher: Dove Press
  • Journal: Journal of Experimental Pharmacology, volume 4, pages 77-83 (issn: 1179-1454, eissn: 1179-1454)
  • Related identifiers: pmc: PMC4863547, doi: 10.2147/JEP.S28907
  • Subject: Review | smooth muscle | vasoconstriction | hypertension | Journal of Experimental Pharmacology | ERK

Richard E RobertsSchool of Biomedical Sciences, University of Nottingham, Nottingham, United KingdomAbstract: Hypertension is a risk factor for myocardial infarction, stroke, renal failure, heart failure, and peripheral vascular disease. One feature of hypertension is a hyperresponsiveness to contractile agents, and inhibition of vasoconstriction forms the basis of some of the treatments for hypertension. Hypertension is also associated with an increase in the growth and proliferation of vascular smooth muscle cells, which can lead to a thickening of the smooth muscle layer of the blood vessels and a reduction in lumen diameter. Targeting both the enhanced contractile responses, and the increased vascular smooth muscle cell growth could potentially be an important pharmacological treatment of hypertension. Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family that is involved in both vasoconstriction and vascular smooth muscle cell growth and this, therefore, makes it an attractive therapeutic target for treatment of hypertension. ERK activity is raised in vascular smooth muscle cells from animal models of hypertension, and inhibition of ERK activation reduces both vascular smooth muscle cell growth and vasoconstriction. This review discusses the potential for targeting ERK activity in the treatment of hypertension.Keywords: ERK, hypertension, smooth muscle, vasoconstriction
  • References (60)
    60 references, page 1 of 6

    1. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75(1):50-83.

    2. Cobb MH. MAP kinase pathways. Prog Biophys Mol Biol. 1999;71(3-4): 479-500.

    3. Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene. 2007;26(22):3100-3112.

    4. Hawes BE, Luttrell LM, van Biesen T, Lefkowitz RJ. Phosphatidylinositol 3-kinase is an early intermediate in the Gβγ-mediated mitogen-activated protein kinase signaling pathway. J Biol Chem. 1996;271(21):12133-12136.

    5. YamanakaY, Hayashi K, Komurasaki T, Morimoto S, Ogihara T, Sobue K. EGF family ligand-dependent phenotypic modulation of smooth muscle cells through EGF receptor. Biochem Biophys Res Commun. 2001; 281(2):373-377.

    6. Eguchi S, Numaguchi K, Iwasaki H, et al. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin IIinduced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem. 1998;273(15):8890-8896.

    7. Eguchi S, Dempsey PJ, Frank GD, Motley ED, Inagami T. Activation of MAPKs by angiotensin II in vascular smooth muscle cells. Metalloprotease-dependent EGF receptor activation is required for activation of Erk and p38 MAPK but not for JNK. J Biol Chem. 2001; 276(11):7957-7962.

    8. Gao Y, Tang S, Zhou S, Ware A. The thromboxane A2 receptor activates mitogen-activated protein kinase via protein kinase C-dependent Gi coupling and Src-dependent phosphorylation of the epidermal growth factor receptor. J Pharmacol Exp Ther. 2001;296(2):426-433.

    9. Zwick E, Hackel PO, Prenzel N, Ullrich A. The EGF receptor as central transducer of heterologous signalling systems. Trends Pharmacol Sci. 1999;20(10):408-412.

    10. Lais LT, Brody MJ. Mechanism of vascular hyperresponsiveness in the spontaneously hypertensive rat. Circ Res. 1975;36(6 Suppl 1): 216-222.

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