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Wnt\u2010Fzd signalling primarily involves a canonical pathway, with dishevelled\u20101\u2010dependent nuclear translocation of \u03b2\u2010catenin that derepresses Wnt\u2010sensitive gene transcription, but can also include non\u2010canonical pathways via phospholipase\u2010C\/Ca<jats:sup>2+<\/jats:sup>mobilization and dishevelled\u2010protein activation of small GTPases. Wnt\u2010Fzd effects vary with specific ligand\/receptor interactions and associated downstream pathways. This paper reviews the biochemistry and physiology of the Wnt\u2010Fzd complex, and presents current knowledge of Wnt signalling in cardiac remodelling processes such as hypertrophy and fibrosis, as well as disease states such as myocardial infarction (MI), heart failure and arrhythmias. Wnt signalling is activated during hypertrophy; inhibiting Wnt signalling by activating glycogen synthase kinase attenuates the hypertrophic response. Wnt signalling has complex and time\u2010dependent actions post\u2010MI, so that either beneficial or harmful effects might result from Wnt\u2010directed interventions. Stem cell biology, a promising area for therapeutic intervention, is highly regulated by Wnt signalling. The Wnt system regulates fibroblast function, and is prominently altered in arrhythmogenic ventricular cardiomyopathy, a familial disease involving excess deposition of fibroadipose tissue. Wnt signalling controls connexin43 expression, thereby contributing to the regulation of cardiac electrical stability and arrhythmia generation. Although much has been learned about Wnt\u2010Fzd signalling in hypertrophy and infarction, its role is poorly understood for a broad range of other heart disorders. Much more needs to be learned for its contributions to be fully appreciated, and to permit more effective exploitation of its enormous potential in therapeutic development.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.235382","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T11:53:16Z","timestamp":1354621996000},"page":"1409-1432","source":"Crossref","is-referenced-by-count":136,"title":["Role of the Wnt\u2010Frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous 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