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. 2019 Apr 26;6:51. doi: 10.3389/fcvm.2019.00051

Figure 4.

Figure 4

Proposed model of LRP1 involvement in the inflammatory phase following AMI. (A) After ligand binding, LRP1 undergoes proteolysis by γ-secretases, the intracellular domain (LRP-ICD) migrates to the nucleus binding to the interferon regulatory factor-3 (IRF-3) and promoting IRF-3 nuclear export and proteasomal degradation, thus reducing the expression of pro-inflammatory genes. The LRP1-agonist complex also inhibits the interleukin-1 receptor associated kinase-1 (IRAK-1), leading to an inhibitory signal on nuclear factor-kappa B (NF-κB). In addition, multiple toll-like receptors (TLRs) have the ability to activate LRP1 which, in turn, stimulates downstream Akt/mTOR signaling which biases cytokine production outputs and restrains the inflammatory response. (B) LRP1 also appears to facilitate the M1/M2 macrophage conversion, promoting the development of an anti-inflammatory M2 functional phenotype. (C) As a result of LRP1-induced anti-inflammatory signaling, leukocyte infiltration in the infarcted myocardium is reduced.