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

Thi Tran (1) , Calypso Mathieu (2) , Magali Torres (1) , Béatrice B. Loriod (1) , Linh Thuy Lê (1) , Catherine Nguyen (1) , Monique Bernard (3) , Marc Leone (2, 4) , Nathalie Lalevee (1)

1 TAGC - Theories and Approaches of Genomic Complexity
2 Service Anesthésie et Réanimation [Hôpital Nord - APHM]
3 CRMBM - Centre de résonance magnétique biologique et médicale
4 MEPHI - Microbes évolution phylogénie et infections

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.

Mots clés: Genes; Dimorphism; Sex; Sepsis; Beta-blocker; Transcriptome Background

Domaines: Sciences du Vivant [q-bio]

Thi Tran, Calypso Mathieu, Magali Torres, Béatrice B. Loriod, Linh Thuy Lê, et al.. Effect of landiolol on sex-related transcriptomic changes in the myocardium during sepsis. Intensive Care Medicine Experimental, 2019, 7 (1), ⟨10.1186/s40635-019-0263-0⟩. ⟨hal-02279120⟩