In mammals, most cardiomyocytes (CMs) become polyploid (they have more than two complete sets of chromosomes). The purpose of this review is to evaluate assumptions about CM ploidy that are commonly discussed, even if not experimentally demonstrated, and to highlight key issues that are still to be resolved. Topics discussed here include (a) technical and conceptual difficulties in defining a polyploid CM, (b) the candidate role of reactive oxygen as a proximal trigger for the onset of polyploidy, (c) the relationship between polyploidization and other aspects of CM maturation, (d) recent insights related to the regenerative role of the subpopulation of CMs that are not polyploid, and (e) speculations as to why CMs become polyploid at all. New approaches to experimentally manipulate CM ploidy may resolve some of these long-standing and fundamental questions.
Keywords: binucleated; cardiomyocyte ploidy; cardiomyocyte proliferation; heart regeneration; mononuclear diploid.