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Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy.


ABSTRACT: Cardiac hypertrophy (CH) is an important and independent predictor of morbidity and mortality. Through expression profiling, we recently identified a subset of genes (Dhrs7c, Decr, Dhrs11, Dhrs4, Hsd11b1, Hsd17b10, Hsd17b8, Blvrb, Pecr), all of which are members of the short-chain dehydrogenase/reductase (SDR) superfamily and are highly expressed in the heart, that were significantly dysregulated in a rat model of CH caused by severe aortic valve regurgitation (AR). Here, we studied their expression in various models of CH, as well as factors influencing their regulation. Among the nine SDR genes studied, all but Hsd11b1 were down-regulated in CH models (AR rats or mice infused with either isoproterenol or angiotensin II). This regulation showed a clear sex dimorphism, being more evident in males than in females irrespective of CH levels. In neonatal rat cardiomyocytes, we observed that treatment with the ?1-adrenergic receptor agonist phenylephrine mostly reproduced the observations made in CH animals models. Retinoic acid, on the other hand, stimulated the expression of most of the SDR genes studied, suggesting that their expression may be related to cardiomyocyte differentiation. Indeed, levels of expression were found to be higher in the hearts of adult animals than in neonatal cardiomyocytes. In conclusion, we identified a group of genes modulated in animal models of CH and mostly in males. This could be related to the activation of the fetal gene expression program in pathological CH situations, in which these highly expressed genes are down-regulated in the adult heart.

SUBMITTER: Roussel E 

PROVIDER: S-EPMC6168690 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy.

Roussel Elise E   Drolet Marie-Claude MC   Lavigne Anne-Marie AM   Arsenault Marie M   Couet Jacques J  

FEBS open bio 20180917 10


Cardiac hypertrophy (CH) is an important and independent predictor of morbidity and mortality. Through expression profiling, we recently identified a subset of genes (<i>Dhrs7c</i>, <i>Decr</i>, <i>Dhrs11</i>, <i>Dhrs4</i>, <i>Hsd11b1</i>, <i>Hsd17b10</i>, <i>Hsd17b8</i>, <i>Blvrb</i>, <i>Pecr</i>), all of which are members of the short-chain dehydrogenase/reductase (SDR) superfamily and are highly expressed in the heart, that were significantly dysregulated in a rat model of CH caused by severe  ...[more]

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