Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling

Puhl, Sarah-Lena; Hilby, Michael; Kohlhaas, Michael; Keidel, Linus M.; Jansen, Yvonne; Hristov, Michael; Schindler, Jakob; Maack, Christoph und Steffens, Sabine (2021): Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling. In: Scientific reports, Bd. 11, Nr. 1, 14385

Abstract

While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Global GPR55-/- and wildtype (WT) mice were basally characterized or assigned to 1, 3 or 28~days permanent MI and subsequently analysed via pro-inflammatory and pro-hypertrophic parameters. GPR55-/- deficiency was basally associated with bradycardia, increased diastolic LV volume and sarcomere length and a subtle inflammatory phenotype. While infarct size and myeloid cell infiltration were unaffected by GPR55 depletion, acute cardiac chemokine production was prolonged post-MI. Concurrently, GPR55-/- hearts exhibited a premature expansion of pro-reparative and phagocytic macrophages paralleled by early up-regulation of extracellular matrix (ECM) factors 3~days post-MI, which could be mimicked by sole haematopoietic GPR55 depletion. Moreover, global GPR55 deficiency mitigated MI-induced foetal gene re-programming and cardiomyocyte hypertrophy, culminating in aggravated LV dilatation and infarct expansion. GPR55 regulates cardiac homeostasis and ischaemia responses by maintaining adequate LV filling and modulating three crucial processes post-MI: wound healing kinetics, cardiomyocyte hypertrophy and maladaptive remodelling.

• Dokumententyp: Zeitschriftenartikel
• Sprache: Englisch