The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection

J Clin Invest. 2021 Dec 15;131(24):e142883. doi: 10.1172/JCI142883.


Chronic inflammation is a hallmark of atherosclerosis and results from an imbalance between proinflammatory and proresolving signaling. The human GPR32 receptor, together with the ALX/FPR2 receptor, transduces biological actions of several proresolving mediators that stimulate resolution of inflammation. However, since no murine homologs of the human GPR32 receptor exist, comprehensive in vivo studies are lacking. Using human atherosclerotic lesions from carotid endarterectomies and creating a transgenic mouse model expressing human GPR32 on a Fpr2×ApoE double-KO background (hGPR32myc×Fpr2-/-×Apoe-/-), we investigated the role of GPR32 in atherosclerosis and self-limiting acute inflammation. GPR32 mRNA was reduced in human atherosclerotic lesions and correlated with the immune cell markers ARG1, NOS2, and FOXP3. Atherosclerotic lesions, necrotic core, and aortic inflammation were reduced in hGPR32mycTg×Fpr2-/-×Apoe-/- transgenic mice as compared with Fpr2-/-×Apoe-/- nontransgenic littermates. In a zymosan-induced peritonitis model, the hGPR32mycTg×Fpr2-/-×Apoe-/- transgenic mice had reduced inflammation at 4 hours and enhanced proresolving macrophage responses at 24 hours compared with nontransgenic littermates. The GPR32 agonist aspirin-triggered resolvin D1 (AT-RvD1) regulated leukocyte responses, including enhancing macrophage phagocytosis and intracellular signaling in hGPR32mycTg×Fpr2-/-×Apoe-/- transgenic mice, but not in Fpr2-/-×Apoe-/- nontransgenic littermates. Together, these results provide evidence that GPR32 regulates resolution of inflammation and is atheroprotective in vivo.

Keywords: Atherosclerosis; Cardiology; G protein–coupled receptors; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / prevention & control
  • Disease Models, Animal
  • Docosahexaenoic Acids / genetics
  • Docosahexaenoic Acids / metabolism
  • Female
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Knockout, ApoE
  • Peritonitis / chemically induced
  • Peritonitis / genetics
  • Peritonitis / metabolism
  • Phagocytosis / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / genetics*


  • GPR32 protein, human
  • Receptors, G-Protein-Coupled
  • resolvin D1
  • Docosahexaenoic Acids

Grants and funding