Another activity for the cardiac biologist: CARP fishing
Authors: S Baudet
Journal: Cardiovascular Research (2003)

See article by Zolk et al. [11] (pages 563-572) in thisanalogy with re-expression of foetal genes in several issue.cardiac pathologies, it was logical to assess CARP expres-Despite several major advances in the management of sion in similar situations.Thus Eschenhagen's group [8] congestive heart failure such as the introduction of an-demonstrated that CARP expression, at the mRNA and giotensin-converting enzyme inhibitors and beta-blockers, protein levels, was increased in failing ventricular muscle the prognosis of CHF remains poor and a major public from dogs submitted to rapid ventricular pacing as well as health issue in westernised countries [1].Accordingly, in explanted ventricular muscle from patients suffering improved long-term pharmacological management of car-from various causes of heart failure.Increased CARP diac diseases will require new research characterised by mRNA was also reported in hypertrophied mouse hearts basic work on the pathophysiology of the diseased car-overexpressing calsequestrin [9] or submitted to stimuli diomyocyte.promoting cardiac hypertrophy [10].Heart failure often results from long-term consequences Data clearly converge to point out the existence of a link of haemodynamic overload, which creates a mechanical between CARP re-expression and various cardiac insults.stress on the cardiomyocytes.One of the earliest responsesThe next logical question was then to know whether CARP of the latter to this insult is reactivation of the foetal genes re-activation was only a marker of cardiac damage or program, preceded by activation of transcription factors whether it had functional consequences, knowing the [2].In most of these instances, reactivation of the foetal repressor role of CARP on the expression of several genes is transient and with no obvious link with the contractile proteins (ventricular isoform of myosin light progressive deterioration of cardiac function.Nevertheless, chain 2 or cardiac troponin C), as demonstrated in rodents.some other genes are activated for long periods of time [3].In this issue of Cardiovascular Research, the report Follow-up of the expression profile of these genes could from Zolk et al. [11] shows, for the first time, short-term serve as a dynamic marker of the transition from hy-contractile effects of CARP overexpression, in addition to pertrophy to cardiac failure and help to identify potential a new pathway of CARP gene expression mediated by pharmacological targets.beta-adrenoceptors.These results and conclusions have Among these newly discovered genes, the nuclear-spe-been gained from several approaches combining in vivo cific transcription factor CARP (''cardiac adriamycin-re-(adult rats made hypertensive by osmotic pump-driven sponsive protein' ' [4] or ''cardiac ankyrin repeat protein'' infusion of low dose isoprenaline for 4 days) and in vitro [5]) could be such a candidate.In fact, in the search for the investigations such as adenovirally-mediated overexpresmolecular pathways guiding ventricular chamber specifica-sion of CARP into neonatal rat cardiomyocytes cultured tion and morphogenesis in rodents, Jeyaseelan and co-from 2 to 12 days.Functional consequences of CARP workers [4], simultaneously with Zou et al. [5], identified a overexpression were particularly elegantly investigated as gene coding for the nuclear protein CARP, whose expres-it involved incorporation of CARP-overexpressing neonatsion was stimulated by the homeobox gene product Csx / al rat cardiomyocytes into a collagen gel, leading to an Nkx2-5.These works also demonstrated that CARP activa-engineered cardiac tissue with measurable contractile tion was accompanied by repressed expression of the properties.These approaches led to two key issues.Firstly, ventricular isoform of myosin light chain 2, atrial nat-CARP gene expression was controlled in part by betariuretic factor and cardiac troponin C genes.Since that adrenergic stimulation.Thus chronically isoprenaline-ininitial discovery, several groups have confirmed the ex-fused rats presented an increase expression (although of pression of CARP in foetal and adult hearts [6,7].By variable extent) of ventricular CARP protein (relative to calsequestrin) and mRNA (relative to GADPH).These