Innate Immune Receptors, Key Actors in Cardiovascular Diseases

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death in the industrialized world. Most CVDs are associated with increased inflammation that arises mainly from innate immune system activation related to cardiac damage. Sustained activation of the innate immune system frequently results in maladaptive inflammatory responses that promote cardiovascular dysfunction and remodeling. Much research has focused on determining whether some mediators of the innate immune system are potential targets for CVD therapy. The innate immune system has specific receptors-termed pattern recognition receptors (PRRs)-that not only recognize pathogen-associated molecular patterns, but also sense danger-associated molecular signals. Activation of PRRs triggers the inflammatory response in different physiological systems, including the cardiovascular system. The classic PRRs, toll-like receptors (TLRs), and the more recently discovered nucleotide-binding oligomerization domain-like receptors (NLRs), have been recently proposed as key partners in the progression of several CVDs (e.g., atherosclerosis and heart failure). The present review discusses the key findings related to the involvement of TLRs and NLRs in the progression of several vascular and cardiac diseases, with a focus on whether some NLR subtypes (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing receptor 3 and nucleotide-binding oligomerization domain-containing protein 1) can be candidates for the development of new therapeutic strategies for several CVDs.

Keywords: AMI, acute myocardial infarction; CARD, caspase activation and recruitment domain; CVD, cardiovascular disease; Ca2+, calcium ion; DAMPs, danger-associated molecular patterns; DAP, D-glutamyl-meso-diaminopimelic acid; ER, endoplasmic reticulum; HF, heart failure; I/R, ischemia/reperfusion; IL, interleukin; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells; NLR, nucleotide-binding oligomerization domain-like receptors; NLRP, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing receptor; NLRP3; NOD, Nucleotide-binding oligomerization domain-containing protein; NOD1; PAMP, pathogen-associated molecular pattern; ROS, reactive oxygen species; SR, sarcoplasmic reticulum; TLR, toll-like receptor; cardiovascular disease; innate immune system; nucleotide-binding oligomerization domain-like receptors; toll-like receptors.