Author + information
- Received February 24, 2020
- Revision received March 19, 2020
- Accepted March 19, 2020
- Published online July 27, 2020.
- Rafael I. Jaén, BSca,b,∗,
- Almudena Val-Blasco, PhDc,∗,
- Patricia Prieto, PhDa,b,d,∗∗∗ (, )@IIBmCSICUAM,
- Marta Gil-Fernández, BScb,c,
- Tarik Smani, PhDb,e,
- José Luis López-Sendón, MD, PhDb,f,
- Carmen Delgado, PhDa,b,
- Lisardo Boscá, PhDa,b and
- María Fernández-Velasco, PhDb,c,∗ (, )@IdipazScience@CIBER_CV@Mfvlorenzo
- aBiomedical Research Institute “Alberto Sols” CSIC-UAM, Madrid, Spain
- bCIBER Cardiovascular (CIBER-CV, ISCIII), Madrid, Spain
- cInnate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain
- dPharmacology, Pharmacognosy and Botany department, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain
- eDepartment of Medical Physiology and Biophysics, Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain
- fServicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain
• The present review recapitulates relevant findings related to the role of the receptors of the innate immune system (TLRs and NLRs) in the progression of the most prevalent CVDs.
• TLRs and NLRs play a key role in the progression of atherosclerosis, acute myocardial infarction or heart failure.
• The development of new specific strategies to impair exacerbated TLR and NLR activation in CVDs are strong candidates for therapy and opens a new research field.
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.
- cardiovascular disease
- innate immune system
- nucleotide-binding oligomerization domain-like receptors
- toll-like receptors
↵∗ Drs. Jaén, Val-Blasco, and Prieto contributed equally to this work and are joint first authors.
This work was supported by the Spanish Ministry of Economy and Competitiveness (AEI/EU) and FEDER: SAF2017-82436R and RTC2017-6283), S2017/BMD-3686 from Comunidad de Madrid, ISCIII (PI17/01344), Fondo Social Europeo (FSE), and CIBERCV, a network funded by ISCIII. Dr. Fernández-Velasco is a Miguel Servet II researcher of ISCIII (MSII16/00047 Carlos III Health Institute). Dr. Jaén holds a FPU fellowship from MECD (Spain). Dr. López-Sendón has received research grants from Sanofi, Boehringer Ingelheim, Amgen, Pfizer, Bayer, and Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received February 24, 2020.
- Revision received March 19, 2020.
- Accepted March 19, 2020.
- 2020 The Authors