Effect of Colchicine on MMP-9, NOX2, and TGF-β1 in Myocardial Infarct
Status:
Recruiting
Trial end date:
2023-02-01
Target enrollment:
Participant gender:
Summary
Reducing NOX-2, MMP-9, and TGF-β1 Expression in Preventing Ventricular Remodelling Post Acute
ST-Segment Elevation Myocardial Infarction using Colchicine (Post Late Reperfusion
Percutaneous Coronary Intervention and Non-Reperfusion and In Vitro Study on Ischemic Rat
Cardiomyocyte Culture Model). Coronary heart disease (CHD) is the most common cause of
mortality and disability worldwide. The handling of reperfusion in Indonesia is still far
below the required standard. Most STEMI patients in Indonesia arrive late to a health
facility with symptoms that have been present for more than 12 hours (late-onset). Heart
failure following a myocardial infarction is one of the long-term complications of STEMI.
Patients with STEMU who do not receive reperfusion were more likely to develop this
consequence. According to several studies, microtubules in cardiomyocytes have been
identified as an essential regulator of cardiomyocytes' ability to respond to shear stress,
which offers compression resistance and facilitates mitochondrial energy production.
Microtubule densification, which occurs due to remodelling in heart failure, disrupts the
microtubule network. The role of reactive oxygen species (ROS) produced by ischemic
myocardium in this remodelling is thus inextricably linked. NADPH oxidase is one of the
enzymes involved (NOX). NOX-2 levels have been reported to be higher in myocardial infarction
and cardiac remodelling, and it has a close interaction with microtubule network, with damage
of microtubule tissue increasing NOX-2 generation of reactive oxygen species. By eroding the
ECM and triggering cytokines and chemokines to recruit inflammatory cells to eliminate
necrotic cardiomyocytes, matrix metalloproteinase 9 (MMP-9) aids tissue rebuilding. Induction
and activation of endogenous TGF-signaling pathways after myocardial infarction have also
been discovered to play a function. TGF-β may play a role in the resolution of the
inflammatory response in the early stages of infarct repair by inactivating macrophages and
decreasing endothelial cell chemokine and cytokine production. TGF-β stimulates the
fibrogenic pathway by causing extracellular matrix deposition and fibrosis later. Colchicine
is a commonly prescribed anti-inflammatory medication with a low cost. the mechanism of
colchicine is tubulin binding, which prevents microtubule assembly and polymerization.
Colchicine inhibits microtubule development at low concentrations and promotes microtubule
depolymerization at higher concentrations. Several studies have demonstrated that low-dose
colchicine can help reduce severe cardiac outcomes such as cardiovascular mortality, stroke,
and cardiac arrest following myocardial infarction. Colchicine is known to cause partial
restoration of microtubule tissue in the perinuclear region. Colchicine has also been shown
in earlier research to reduce the expression of MMP-9, NOX2, and TGF-β This study aims to
evaluate whether colchicine could prevent ventricular remodelling in STEMI patients with
delayed reperfusion and non reperfusion. The minor hypothesis of this study was colchicine
can lower NOX-2, MMP-9, and TGF-β expression in the clinical situation of patients with
delayed and non-reperfusion STEMI following PCI. Randomization with 1:1 allocation were used
to classify the patients, each group include 41 patients with one group receiving colchicine
therapy and standard therapy and the other receiving standard therapy only. Colchicine
administration was the independent variable. STEMI patients with delayed and non-reperfusion
IKP who met the inclusion criteria are included in this randomized clinical trial. Left
ventricular end-diastolic volume (LVEDV) was the dependent variable while serum MMP-9, NOX-2,
and TGF-β were the intermediate variables. In the treatment group, colchicine 1 mg is
administered before PCI or admission to the ICCU, and colchicine is continued at 0.5 mg/day
for a month. Within 24 to 36 hours of treatment initiation, the patient had echocardiography,
NOX-2, MMP-9, and TGF-β levels evaluated. On days 4-5, a second NOX-2, MMP-9, and TGF-β
screening were performed. The follow up two months after treatment initiation includes an
assessment of drug compliance, symptoms, and echocardiography. Depending on the normality of
the data distribution, the difference between groups is performed using the unpaired T-test
or the Mann-Whitney test. The significant difference between the treatment groups is
indicated by a p-value of 0.05.