Effect of landiolol on sex-related transcriptomic changes in the myocardium during sepsis

Autor: Tran, Thi Thom, Mathieu, Calypso, Torres, Magali, Loriod, Béatrice, Lê, Linh Thuy, Nguyen, Catherine, Bernard, Monique, Leone, Marc, Lalevée, Nathalie
Přispěvatelé: Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Spinelli, Lionel, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: INTENSIVE CARE MEDICINE EXPERIMENTAL
INTENSIVE CARE MEDICINE EXPERIMENTAL, Springer, 2019, 7 (1), ⟨10.1186/s40635-019-0263-0⟩
INTENSIVE CARE MEDICINE EXPERIMENTAL, 2019, 7 (1), ⟨10.1186/s40635-019-0263-0⟩
Intensive Care Medicine Experimental, Vol 7, Iss 1, Pp 1-14 (2019)
Intensive Care Medicine Experimental
ISSN: 2197-425X
DOI: 10.1186/s40635-019-0263-0⟩
Popis: Objectives The aims of this study are to better understand phenotypic differences between male and female rats during sepsis, to characterise the contribution of the beta1-adrenergic blocker landiolol to septic cardiomyopathy and to determine why landiolol induces divergent effects in males and females. Methods The myocardial transcriptional profiles in male and female Wistar rats were assessed after the induction of sepsis by cecal ligation and puncture and addition of landiolol. Results Our results showed major differences in the biological processes activated during sepsis in male and female rats. In particular, a significant decrease in processes related to cell organisation, contractile function, ionic transport and phosphoinositide-3-kinase/AKT (PI3K/AKT) signalling was observed only in males. The transcript of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 (SERCA3) was sex-differently regulated. In males, landiolol reversed several signalling pathways dysregulated during sepsis. The expression level of genes encoding tubulin alpha 8 (TUBA8) and myosin heavy chain 7B (MYH7) contractile proteins, phosphatase 2 catalytic subunit alpha (PPP2CA), G protein-coupled receptor kinase 5 (GRK5) and A-kinase anchoring protein 6 (AKAP6) returned to their basal levels. In contrast, in females, landiolol had limited effects. Conclusion In males, landiolol reversed the expression of many genes that were deregulated in sepsis. Conversely, sepsis-induced deregulation of gene expression was less pronounced in females than in males, and was maintained in the landiolol-treated females. These findings highlight important sex-related differences and confirm previous observations on the important benefit of landiolol intake on cardiac function in male rats. Electronic supplementary material The online version of this article (10.1186/s40635-019-0263-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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