Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives
Abstract
1. Introduction
2. Inflammasomes
3. Inflammasomes and CVDs
3.1. Atherosclerosis
3.2. Heart Failure
3.3. Atrial Fibrillation
3.4. Chronic Kidney Disease and the NLRP3 Inflammasome
4. Special Focus: Pericarditis and Still’s Disease
5. New Pharmacology Strategies
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AIM2 | Absent in Melanoma 2 |
ASC | Apoptosis-associated Speck-like protein containing a CARD |
AS | Atherosclerosis |
AOSD | Adult-Onset Still’s Disease |
CAD | Coronary Artery Disease |
CARD | Caspase Activation and Recruitment Domain |
CKD | Chronic Kidney Disease |
CVD | Cardiovascular Disease |
DAMPs | Damage-Associated Molecular Patterns |
ER | Endoplasmic Reticulum |
FMF | Familial Mediterranean Fever |
GSDMD | Gasdermin D |
HF | Heart Failure |
HFpEF | Heart Failure with Preserved Ejection Fraction |
HFrEF | Heart Failure with Reduced Ejection Fraction |
HIF-1α | Hypoxia-Inducible Factor 1-alpha |
HMGB1 | High-Mobility Group Box 1 |
IL | Interleukin |
IR | Ischemia-Reperfusion |
MAPK | Mitogen-Activated Protein Kinase |
NACHT | Domain present in NAIP, CIITA, HET-E, and TP1 |
NF-κB | Nuclear Factor kappa-light-chain-enhancer of activated B cells |
NLRC4 | NOD-Like Receptor Family CARD Domain Containing 4 |
NLRP3 | NOD-Like Receptor Protein 3 |
NSAIDs | Non-Steroidal Anti-Inflammatory Drugs |
PAMPs | Pathogen-Associated Molecular Patterns |
PPAR-γ | Peroxisome Proliferator-Activated Receptor Gamma |
PRRs | Pattern Recognition Receptors |
PYD | Pyrin Domain |
RAAS | Renin-Angiotensin-Aldosterone System |
ROS | Reactive Oxygen Species |
SGLT2 | Sodium-Glucose Cotransporter 2 |
TGF-β | Transforming Growth Factor Beta |
TLRs | Toll-Like Receptors |
TNF | Tumor Necrosis Factor |
TXNIP | Thioredoxin-Interacting Protein |
VEGF-A | Vascular Endothelial Growth Factor A |
VLDL | Very Low-Density Lipoprotein |
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Trigger | Sensor/Pathway | Key Molecules | Downstream Effect | Associated Conditions | References |
---|---|---|---|---|---|
Cholesterol crystals | Lysosomal rupture | NLRP3, ASC, caspase-1 | IL-1β, IL-18 release, pyroptosis | Atherosclerosis | [44,46] |
ROS/oxidative stress | ROS–TXNIP–NLRP3 | TXNIP, NLRP3, caspase-1 | Inflammation, fibrosis | Heart failure, CKD | [19,20] |
Mitochondrial dysfunction | mtROS, mtDNA | NLRP3, GSDMD | Pyroptosis, cytokine secretion | AF, HF, CKD | [19] |
ER stress | Ca2+ signaling | NLRP3 | IL-1β production, cell damage | CKD, myocardial injury | [23,24] |
Uric acid/ATP | P2X7 receptor activation | K+ efflux, NLRP3 | Inflammasome priming/activation | Pericarditis, CKD | [19,88] |
Mechanical stretch | Ion channels, ROS | NLRP3, NF-κB | Fibrosis, arrhythmias | Atrial fibrillation | [76,79,81] |
Molecule | Target | Type of Study | References |
---|---|---|---|
Anti-SGLT-2 | Sodium–glucose cotransporter-2 | Clinical | [101] |
Anakinra, Canakinumab | IL-1 | Clinical | [104,105] |
Colchicine | Interacts with tubulin and thereby inhibits microtubule-dependent functions in rapidly proliferating cells | Preclinical in vitro | [108] |
TAK-242 (resatorvid) | TLR4 | Preclinical | [121] |
MCC950 | NACHT domain of NLRP3. | Review of preclinical studies | [123] |
Oridonin | NACHT domain of NLRP3 | Preclinical | [124] |
OLT1177 | Inhibits ASC oligomerization | Preclinical | [126] |
Disulfiram | Causes autophagy in a variety of macrophages, smooth muscle cells, endothelial cells, hepatocytes, and tissue samples from atherosclerotic plaques | Preclinical | [127] |
BAY 11-7082 | Inhibits NF-κB | Preclinical | [132] |
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Caldarelli, M.; Franza, L.; Cutrupi, S.; Menegolo, M.; Franceschi, F.; Gasbarrini, A.; Gambassi, G.; Cianci, R. Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives. Int. J. Mol. Sci. 2025, 26, 5439. https://doi.org/10.3390/ijms26125439
Caldarelli M, Franza L, Cutrupi S, Menegolo M, Franceschi F, Gasbarrini A, Gambassi G, Cianci R. Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives. International Journal of Molecular Sciences. 2025; 26(12):5439. https://doi.org/10.3390/ijms26125439
Chicago/Turabian StyleCaldarelli, Mario, Laura Franza, Sebastiano Cutrupi, Martina Menegolo, Francesco Franceschi, Antonio Gasbarrini, Giovanni Gambassi, and Rossella Cianci. 2025. "Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives" International Journal of Molecular Sciences 26, no. 12: 5439. https://doi.org/10.3390/ijms26125439
APA StyleCaldarelli, M., Franza, L., Cutrupi, S., Menegolo, M., Franceschi, F., Gasbarrini, A., Gambassi, G., & Cianci, R. (2025). Inflammasomes in Cardiovascular Diseases: Current Knowledge and Future Perspectives. International Journal of Molecular Sciences, 26(12), 5439. https://doi.org/10.3390/ijms26125439