Interleukin Receptor Associated Kinase 1 Signaling and Its Association with Cardiovascular Diseases

Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) directly interact with intracellular interleukin receptor associated kinase (IRAK) family members to initialize innate immune and inflammatory responses following activation by pathogen-associated or host-derived elements. Although four IRAK family members [IRAK1, 2, 3 (i.e., IRAK-M), and 4] are involved in TLR and IL-1R signaling pathways, IL-1R $>$ IRAK1 signaling appears to be the most studied pathway, with sufficient evidence to support its central role linking the innate immune response to the pathogenesis of various diseases, including cancers, metabolic disorders, and non-infectious immune disorders. However, IRAK1’s involvement in cardiovascular diseases was only recently revealed and the detailed mechanism underling the pathogenesis of cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure (all non-infectious disorders), remains largely unknown with very limited publications to date. This review aims to summarize the overall roles of the IRAK family, especially IRAK1, in mediating the development of cardiovascular diseases.

Keywords

interleukin-1 receptor associated kinase 1

innate immune response

signaling pathways

toll-like receptor

interleukin-1 receptor

endothelial cells

vascular smooth muscle cells

cardiomyocytes

atherosclerosis

myocardial infarction

heart failure

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

IRAK1-mediated signaling pathways in cardiovascular and immune cells. Injured CMs, ECs, and VSMCs release DAMPs, which then bind to TLRs/IL-1R on immune cells and cardiovascular cells (CMs, ECs, and VSMCs) and activate downstream inflammatory pathways including: (a) IRAK1 $>$ NF- $\kappa{}$ B and MAPK; (b) IRAK1 $>$ JAK and STAT; and (c) IRAK1 $>$ NLRP3 $>$ Caspase 4/5/11, presumably leading to foam cell formation and cardiac cell apoptosis. The schematic cell refers to an immune (e.g., macrophage) cell or a cardiovascular cell (e.g., CM, ECC, and VSCMC). Abbreviations: DAMPs, damage associated molecular patterns; HMGB1, high mobility group box 1; HSP 60/70/72, heat shock protein 60, 70, 72; I/R, ischemia/reperfusion; IL-1/-6/-10/-18/-27, interleukin-6,-10,-18, -27; IL-1R, interleukin-1 receptor; IRAK1/4, interleukin receptor associate kinase 1/4; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation primary response 88; NF- $\kappa{}$ B, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; STAT, signal transducers and activators of transcription; TLRs, toll-like-receptors; TRAF6, tumor necrosis factor receptor-associated factor 6 (The figure was originally created by the authors using BioRender.com online software).

1 of 2

Rev. Cardiovasc. Med. Print ISSN 1530-6550 Electronic ISSN 2153-8174