Signaling pathways activated by vasoactive peptides in the cardiac myocyte and their role in myocardial pathologies.
In addition to its vasoactive effects, endothelin-1 (ET-1) causes hypertrophy of isolated cardiac myocytes. Since the early 1990s, the cell signaling events initiated by the binding of ET-1 to its cell surface receptors on the myocyte, and their roles in myocyte hypertrophy have been a particular interest of mine. ET-1 activates several intracellular signaling pathways in cardiac myocytes, notably the protein kinase C pathway and the mitogen-activated protein kinase cascades. It is likely that activation of these pathways contributes to the hypertrophic response. More recently, ET-1 has been shown to activate the phosphatidylinositol 3-kinase/Akt pathway, although the activation is relatively weak in comparison to other agonists. The actions of 2 other vasoactive peptides, angiotensin II and bradykinin, on the heart or cardiac myocyte in relation to cardiac hypertrophy are also discussed.
Sugden
Peter H
PH
National Heart and Lung Institute Division (Cardiac Medicine Section), Faculty of Medicine, Imperial College of Science, Technology, and Medicine, London, UK.
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction
D019332:Endothelin-1; D000804:Angiotensin II; D011493:Protein Kinase C; D001920:Bradykinin