Table 1.
Preclinical and clinical studies on inflammasome modulation in heart failure.
| Animal Studies | ||||
|---|---|---|---|---|
| Drug Name | Target | Animal Model | Main Findings | References |
| Colchicine | Interference with microtubule polymerization, subsequently disrupting cellular processes involved in the assembly and activation of the NLRP3 inflammasome | Spontaneously hypertensive rats | No effect on active tension or passive stiffness of the left ventricular papillary muscles. | [61] |
| ATII-infused Wistar rats and cardiomyocytes | Improvement in apoptosis markers. | [62] | ||
| I/R injury mouse model | Reduced myocardial infarct size, fibrosis, and inflammatory biomarkers. Improvement in cardiac output. No change in LVEF or diastolic function. |
[63] | ||
| AMI mouse model | Improved LVEDD, LVEF. Lower natriuretic peptides and mortality. Reduced tissue expression of inflammasome components. |
[64] | ||
| Doxorubicin-induced cardiomyopathy mouse model | Improved LVEDD, LVESD, LVEF. Decreased natriuretic peptides, fibrosis area, and expression of NLRP3 inflammasome components. |
[65] | ||
| Hypertension-induced HFpEF rat model | Ameliorated functional capacity and survival. Improved LVEDP, LV mass, BNP. Reduced myocardial inflammation and fibrosis. |
[66] | ||
| MCC950 | Selective NLRP3 inflammasome inhibitor through the prevention of the oligomerization process of NLRP3 | Postmenopausal heart disease mouse model | Attenuated hypertrophy and improvements in myocardial relaxation, fractional shortening, and natriuretic peptides. | [67] |
| Transient aortic constriction-induced pressure overload mouse model | Improved LVEF and cardiac dimensions. Diminished hypertrophy, oxidative stress, inflammation, and fibrosis. |
[68] | ||
| Isoproterenol-induced cardiomyopathy | Improvements in cardiac function, inflammation, oxidative stress, and fibrosis. | [69] | ||
| HFpEF model | Improved pulmonary artery pressure and remodeling. | [70] | ||
| Transient aortic constriction-induced HFpEF mouse model | Lower QTc duration, action potential duration 90, threshold for APD alternans. Decreased rate of ventricular arrhythmia induction. |
[71] | ||
| CY-09 | Prevention of the interaction between NLRP3 and the adapter protein ASC, which is crucial for the assembly and activation of the inflammasome | Ponatinib-induced cardiotoxicity in mice after transient aortic constriction | Improved LVEF and fractional shortening. Diminished myocardial inflammation. |
[72] |
| Dapansutrile | Binding to the NLRP3 protein, preventing its oligomerization, which is necessary for the formation of the inflammasome complex | Non-reperfused ischemic cardiomyopathy mouse model | Improved myocardial contractile reserve, ameliorated diastolic function. | [73] |
| Colchicine | Interference with microtubule polymerization, subsequently disrupting cellular processes involved in the assembly and activation of the NLRP3 inflammasome | RCT of patients with stable congestive HFrEF | No change in functional capacity, hospitalization rates, or mortality. Improved LV dimensions and inflammatory markers. |
[74] |
| Dapansutrile | Binding to the NLRP3 protein, preventing its oligomerization, which is necessary for the formation of the inflammasome complex. | Phase 1 RCT of patients with HFrEF and impaired functional capacity | Improved LVEF and exercise capacity. | [75] |
ATII: angiotensin II; I/R: ischemia–reperfusion; LVEF: left ventricular ejection fraction; AMI: acute myocardial infarction; LVEDD: left ventricular end-diastolic diameter; LVESD: left ventricular end-systolic diameter; HFpEF: heart failure with preserved ejection fraction; BNP: brain natriuretic peptide; RT: randomized controlled trial; HFrEF: heart failure with reduced ejection fraction.