Hildur Arnardottir (Sweden)

Karolinska Institute Department of Medicine
Hildur Arnardottir completed her PhD from the University of Iceland and trained as a Post-doctoral fellow with Prof. Charles N Serhan at Harvard Medical School and Brigham and Women’s Hospital (USA). Her work on omega-3 fatty acids, specialized pro-resolving lipid mediators (SPM) and resolution of inflammation in health and disease has lead to several publications in the field of nutritional biochemistry and resolution biology. She is currently an Assistant Professor of Translational Cardiology, Department of Medicine, Karolinska Institutet (Sweden). Her research efforts are focused on bioactive lipid mediators in cardiovascular diseases, assessing their regulation, cellular targets and molecular mechanism through which they exert their bioactions in the resolution of inflammation and calcification.

Author Of 1 Presentation

 Conference Calendar

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

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 (hGPR32myc×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 hGPR32mycTg×Fpr2-/-×ApoE-/- transgenic mice as compared to Fpr2-/-×ApoE-/- non-transgenic littermates. In a zymosan induced peritonitis model, the hGPR32mycTg×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 hGPR32mycTg×Fpr2-/-×ApoE-/- transgenic mice but not in the Fpr2-/-×ApoE-/- non-transgenic littermates.

Conclusions

Altogether these results provide the first evidence that GPR32 regulates resolution of inflammation and is atheroprotective in vivo.

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Presenter of 1 Presentation

 Conference Calendar

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

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 (hGPR32myc×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 hGPR32mycTg×Fpr2-/-×ApoE-/- transgenic mice as compared to Fpr2-/-×ApoE-/- non-transgenic littermates. In a zymosan induced peritonitis model, the hGPR32mycTg×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 hGPR32mycTg×Fpr2-/-×ApoE-/- transgenic mice but not in the Fpr2-/-×ApoE-/- non-transgenic littermates.

Conclusions

Altogether these results provide the first evidence that GPR32 regulates resolution of inflammation and is atheroprotective in vivo.

Hide