title: Inhibition of angiotensin II-induced cardiac hypertrophy and associated ventricular arrhythmias by a p21 activated kinase 1 bioactive peptide.
abstract: Cardiac hypertrophy increases the risk of morbidity and mortality of cardiovascular disease and thus inhibiting such hypertrophy is beneficial. In the present study, we explored the effect of a bioactive peptide (PAP) on angiotensin II (Ang II)-induced hypertrophy and associated ventricular arrhythmias in in vitro and in vivo models. PAP enhances p21 activated kinase 1 (Pak1) activity by increasing the level of phosphorylated Pak1 in cultured neonatal rat ventricular myocytes (NRVMs). Such PAP-induced Pak1 activation is associated with a significant reduction of Ang II-induced hypertrophy in NRVMs and C57BL/6 mice, in vitro and in vivo, respectively. Furthermore, PAP antagonizes ventricular arrhythmias associated with Ang II-induced hypertrophy in mice. Its antiarrhythmic effect is likely to be involved in multiple mechanisms to affect both substrate and trigger of ventricular arrhythmogenesis. Thus our results suggest that Pak1 activation achieved by specific bioactive peptide represents a potential novel therapeutic strategy for cardiac hypertrophy and associated ventricular arrhythmias.
authors.affiliation: Institute for Cardiovascular Diseases, Union Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medicine and Human Science, University of Manchester, Manchester, United Kingdom; Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
authors.forename: Wee K
authors.initials: WK
authors.lastname: Lin
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medicine and Human Science, University of Manchester, Manchester, United Kingdom.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Sciences, Faculty of Medicine and Human Science, University of Manchester, Manchester, United Kingdom.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute for Cardiovascular Diseases, Union Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Terrar
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
authors.affiliation: Faculty of Life Science, University of Manchester, Manchester, United Kingdom.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology and Biophysics, Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Institute for Cardiovascular Diseases, Union Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China; Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects; D010455:Peptides / Q000378:metabolism* / Q000627:therapeutic use*; D051381:Rats; D054462:p21-Activated Kinases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D010455:Peptides; D000804:Angiotensin II; D054462:p21-Activated Kinases