Magnus Back (Sweden)

Karolinska Institutet Department of Cardiology

Magnus Bäck is Professor of Cardiology at the Karolinska University Hospital and Director of Translational Cardiology Research at the Center for Molecular Medicine at Karolinska Institutet, Stockholm, Sweden. His present work combines clinical cardiology in valvular and coronary disease with translational research on atherosclerosis, aortic valve stenosis, and cardiovascular risk factors, with emphasis on the role of the resolution of inflammation.

Author Of 2 Presentations

Conference Calendar

Impaired resolution of inflammation – role of lipid mediators (ID 1302)

Session Type

Vascular Biology

Session Name

Workshop: Macrophage function and impaired resolution of inflammation in atherosclerosis (ID 11)

Session Time

16:00 - 17:30

Date

Mon, 31.05.2021

Room

Hall E

Lecture Time

16:15 - 16:30

Presenter

Magnus Back (Sweden)

O024 - The resolvin D1 receptor GPR32 transduces inflammation-resolution and atheroprotection (ID 1174)

Session Type

Vascular Biology

Session Name

Workshop: Macrophage function and impaired resolution of inflammation in atherosclerosis (ID 11)

Session Time

16:00 - 17:30

Date

Mon, 31.05.2021

Room

Hall E

Lecture Time

16:38 - 16:46

Presenter

Hildur Arnardottir (Sweden)

Abstract

Abstract

Background and Aims

Chronic inflammation is a hallmark of atherosclerosis and results from an imbalance between pro-inflammatory and pro-resolving signaling. The human GPR32 receptor serves in tandem with the ALX/FPR2 receptor to transduce biological actions of pro-resolving mediators that stimulate resolution of inflammation. However, since no murine homologs of the human GPR32 exist and comprehensive in vivo studies are lacking, we generated a novel transgenic mouse model expressing human GPR32 while lacking Fpr2 on a hyperlipidemic background to investigate the role of GPR32 in vivo.

Methods

Human atherosclerotic lesions from carotid endarterectomies and normal controls were used for mRNA microarray analysis and immunofluoresence staining. A novel transgenic mouse model expressing human GPR32 on a Fpr2×apolipoprotein E double KO background (hGPR32_myc×Fpr2^-/-×ApoE^-/-) was generated. Mice were either subjected to HFD induced atherosclerosis or zymosan peritonitis, and organs collected for cellular and biochemical analysis, e.g. RT-qPCR, immunohistochemistry and fow cytometry.

Results

GPR32 mRNA was reduced in human atherosclerotic lesions and correlated with immune cell markers Arg1, iNOS and FoxP3. Atherosclerotic lesions and aortic inflammation were reduced in hGPR32_mycTg×Fpr2^-/-×ApoE^-/-transgenic mice as compared to Fpr2^-/-×ApoE^-/- non-transgenic littermates. In a zymosan induced peritonitis model, the hGPR32_mycTg×Fpr2^-/-×ApoE^-/- transgenic mice had ~55% less exudate neutrophils at 4h and enhanced pro-resolving macrophage responses at 24h. Treatment with the GPR32 agonist aspirin-triggered resolvin D1 (AT-RvD1) reduced neutrophil numbers in hGPR32_mycTg×Fpr2^-/-×ApoE^-/- transgenic mice but not in the Fpr2^-/-×ApoE^-/- non-transgenic littermates.