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Efficacy of Colchicine in Reducing NT-proBNP, Caspase-1, TGF-β, and Galectin-3 Expression and Improving
Tri Astiawati1,2, Mohammad Saifur Rohman3,4, Titin Wihastuti5
1Doctoral Program of Medical Science, Brawijaya University, Malang 65145, Indonesia.
Abstract:
Background: Caspase-1 (reflects NOD-like receptor protein 3 inflammasome activity), transforming growth factor-β (TGF-β), and Galectin-3 play significant roles in post-AMI fibrosis and inflammation. Recently, colchicine was shown to dampen inflammation after AMI; however, its direct benefit remains controversial. Objectives: This study aimed to analyze the benefit of colchicine in reducing NT-proBNP, Caspase-1, TGF-β,and Galectin-3 expression and improving systolic-diastolic echocardiography parameters among AMI patients. Methods: A double-blinded, placebo-controlled, randomized, multicenter clinical trial was conducted at three hospitals in East Java, Indonesia: Dr. Saiful Anwar Hospital Malang, Dr. Soebandi Hospital Jember, and Dr. Iskak Hospital Tulungagung, between 1 June and 31 December 2023. A total of 161 eligible AMI subjects were randomly allocated 1:1 to colchicine (0.5 mg daily) or standard treatment for 30 days. Caspase-1, TGF-β, and Galectin-3 were tested on day 1 and day 5 by ELISA, while NT-proBNP was tested on days 5 and 30. Transthoracic echocardiography was also performed on day 5 and day 30. Results: By day 30, no significant improvements in systolic-diastolic echocardiography parameters had been shown in the colchicine group. However, colchicine reduced the level of NT-proBNP on day 30 more than placebo (ΔNT-proBNP: -73.74 ± 87.53 vs. -75.75 ± 12.44 pg/mL; p < 0.001). Moreover, colchicine lowered the level of Caspase-1 expression on day 5 and the levels of TGF-β and Galectin-3 expression on day 1. Conclusions: Colchicine can reduce NT-proBNP, Caspase-1, TGF-β, and Galectin-3 expression significantly among AMI patients. Colchicine administration was capable of reducing post-AMI inflammation, ventricular dysfunction, and heart failure but did not improve systolic-diastolic echocardiography parameters (ClinicalTrials.gov identifier: NCT06426537).
Insights
Colchicine effectively reduced NT-proBNP, Caspase-1, TGF-β, and Galectin-3 levels in acute myocardial infarction (AMI) patients, indicating reduced inflammation and ventricular dysfunction. However, it did not improve echocardiography parameters.
Area of Science:
- Cardiology
- Pharmacology
- Inflammation Research
Background:
- Caspase-1, TGF-β, and Galectin-3 are key mediators of post-acute myocardial infarction (AMI) fibrosis and inflammation.
- Colchicine's anti-inflammatory effects post-AMI are under investigation, with its direct clinical benefit remaining debated.
Purpose of the Study:
- To evaluate colchicine's efficacy in reducing NT-proBNP, Caspase-1, TGF-β, and Galectin-3 levels.
- To assess colchicine's impact on echocardiographic parameters in patients following AMI.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 161 AMI patients over 30 days.
- Colchicine (0.5 mg daily) or placebo was administered alongside standard treatment.
- Biomarkers (Caspase-1, TGF-β, Galectin-3, NT-proBNP) and echocardiography were assessed at specified intervals.
Main Results:
- Colchicine significantly reduced NT-proBNP levels by day 30 compared to placebo.
- A significant decrease in Caspase-1 expression was observed by day 5.
- Colchicine lowered TGF-β and Galectin-3 expression levels by day 1.
- No significant improvement in systolic-diastolic echocardiography parameters was noted.
Conclusions:
- Colchicine demonstrates a significant reduction in NT-proBNP, Caspase-1, TGF-β, and Galectin-3 in AMI patients.
- Colchicine may mitigate post-AMI inflammation and ventricular dysfunction.
- Colchicine did not improve systolic-diastolic echocardiographic parameters in this study cohort.
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