Effect Of Colchicine Research Articles

Colchicine inhibits monosodium urate crystal-mediated inflammation by influencing F-actin formation

ObjectivesTo understand the mechanism by which colchicine inhibits the inflammatory properties of monosodium urate (MSU) crystal deposits and tophi. MethodsWe investigated the effects of colchicine on the inflammatory properties of monosodium urate (MSU) crystal deposits in several models: (i) In vitro tophus formation by MSU and neutrophils; (ii) MSU-induced peritonitis model; (iii) Alpha-1-antitrypsin-induced peritoneal MSU flare model; (iv) MSU-induced arthritis model. We measured neutrophil numbers, NET formation, IL-1β production and F-actin generation by MSU crystals. In addition, we tested the effect of actin inhibitors SMIFH2, Cytochalasin B and Latrunculin B in the models. ResultsColchicine did not affect neutrophil numbers in all these models. However, colchicine was highly effective to inhibit NET formation, IL-1β production and F-actin generation indicating less pronounced tophus formation, lower inflammatory properties of tophi and reduced conversion from G-actin into F-actin, respectively. F-actin was shown to accumulate in tophi without presence of colchicine and being resistant to degradation by DNase I. Actin inhibitors SMIFH2 and Cytochalasin B significantly reduced IL-1β and neutrophil elastase levels and mitigated MSU-induced arthritis. ConclusionColchicine effects on gout flares are not based on reducing neutrophil numbers but on changing the functional properties of tophi by reducing their DNase-resistant F-actin concentrations and thereby reducing the negative impact of NETs on IL-1β production and the pro-inflammatory state of tophi. Actin inhibitors may be interesting tools to convey anti-inflammatory properties and reduction of flares in gout patients.

High Colchicine Doses Are Really Silver Bullets Against COVID-19

Abstract The numerous attempts to prove a therapeutic effect of low-dose colchicine for the treatment of Coronavirus disease-2019 (COVID-19) have been discouraging. Increase of doses, however, leads to accumulation in leukocytes and inhibition of the cytokine storm thus preventing COVID-19 complications and hospitalizations. Hospital mortality drops up to 7-fold, while outpatients practically do not reach hospitalization.

Investigating the effects of colchicine on seed germination and morphological traits in durum wheat (Triticum turgidum subs. durum Desf.)

A broader genetic diversity holds great promise for enhancing the productivity of durum wheat, especially under challenging environmental stressors. Establishing an improved genetic pool through the pre-treatment of durum wheat seeds with antimitotic agents, like colchicine, could play a pivotal role in boosting seed germination, seedling growth, morphological characteristics, and overall yield. This study explored the impact of colchicine on seed germination, growth, and morphological traits in two durum wheat cultivars (PDW-233 and DDW-47). For the experiment, presoaked seeds from each cultivar were exposed to different colchicine concentrations (0.1%, 0.2%, and 0.3%) over an 8-hour period. Quantitative traits such as germination percentage, plant survival rate, plant height, tiller number per plant, seeds per spike, and 1000-grain weight were meticulously measured in the treated plants. The results revealed considerable variability in these quantitative traits across the different colchicine treatments in both wheat varieties in the M1 generation. Significant alterations were observed across various concentrations, indicating colchicine’s potential for inducing genetic diversity within a single generation. These findings underscore the effectiveness of colchicine as a mutagenic agent capable of stimulating notable genetic variation, which, with precise selection, can lead to the identification and development of promising high-yield, stress-tolerant mutants in durum wheat. The results of this study suggest that rigorous selection and further breeding of desirable mutants could result in significantly improved and high-yielding durum wheat lines in subsequent generations. Thus, this approach may offer a viable pathway for enhancing durum wheat’s genetic resilience and productivity.

Abstract 4120924: Effect Of Colchicine On Myocardial Infarction: Updated Systematic Review And Meta-analysis Of Randomized Controlled Trials

Background: Colchicine, in multiple ways, has beneficial as well as adverse effects on patients with myocardial infarction. Objective: Our current study aims to study the efficacy as well as harmful effects of colchicine on patients with myocardial infarction. Methods: A comprehensive search was conducted on PubMed, the Cochrane Library, Scopus, Google Scholar, and Clinical trials till May 2024, and Randomized controlled trials were searched investigating the effect of Colchicine on patients with Myocardial Infarction. The quality of trials was assessed with the Cochrane risk of bias tool. Our primary Outcomes include adverse cardiovascular events while secondary outcomes include All-cause Mortality, adverse gastrointestinal effects, levels of hs-CRP, incidence of stroke, cardiac arrest, and hospitalization urgency. Risk ratios and mean differences were pooled under the Random-effect Model. Results: Statistical analysis shows that colchicine did not impact all-cause Mortality (RR =1.00, 95% CI=0.72-1.39, P=0.98, I2=0%), cardiac arrest (RR=0.81, 95% CI=0.33-1.95, P=0.63, I2=0), incidence of stroke(RR=0.45, 95% CI= 0.17-1.19, P=0.11, I2=36%) recurrent myocardial infarction (RR=0.78, 95%CI=0.57-1.06, P=0.11, I2=11%) and levels of hs-CRP (MD= -0.87, 95% CI=-1.80-0.06, P=0.07, I2=67%). However, colchicine shows statistically significant reduction in cardiovascular events(RR=0.75, 95%CI=0.60-0.94 , P=0.01, I2= 48%) , hospitalization urgency(RR=0.46, 95% CI=0.31-0.68, P=0.0001, I2=0%) and statistically significant increase adverse gastrointestinal events (RR=1.86, CI=1.14-3.02, P=0.01, I2=79%). Conclusion: Hence, we conclude that colchicine reduces adverse cardiovascular events, hospitalization urgency and increases adverse gastrointestinal events especially diarrhea in patients with myocardial infarction. However, colchicine did not reduce all-cause deaths, cardiac arrest, stroke incidence, the incidence of recurrent myocardial infarction, and hs-CRP; we still believe that the effect of colchicine on myocardial infarction needs further investigation and encourages the researcher to conduct more trials, especially with long-term follow-up.

Abstract 4124690: Effect of Colchicine on the Perivascular Inflammation Index of Coronary Computerized Tomography Angiogram: COPIX trial

Inflammation is an important pillar of atherogenesis in coronary disease. Studies have documented the prognostic power of measuring the attenuation of coronary perivascular adipose tissue (PVAT) and its good correlation as an early inflammatory biomarker in the atherogenesis process. Colchicine, a medication with well-documented anti-inflammatory action and with an impact on reducing cardiovascular outcomes, may influence reducing FAI (Fat Attenuation index) assessed by coronary tomography angiography. This study aims to evaluate the effect of colchicine in reducing coronary inflammation after 12 months of using the medication. Methods: Single- center, randomized, prospective, open, ongoing study, carried out at the Heart Institute of the University of São Paulo (InCor HCFMUSP). Forty patients with documentation of FAI ≥ 70 HU in the right coronary artery (RCA) and/or left descending artery (LAD) were randomized to receive colchicine 0.5 mg/day for a period of 12 months. The primary outcome was the quantification of FAI in both therapeutic groups (colchicine and control) after a 12-month follow-up. As a secondary outcome, we evaluated the variation in total atheroma volume, calcium score, progression or regression of high plaque findings, variation low attenuation plaque volume and clinical outcomes. Results: Forty patients were included between May 2021 to April 2023, of which 22 were in the Colchicine group and 18 in the Control group. As a primary outcome, no FAI improvement in RCA and LAD was documented after a 12-month follow-up. In the Colchicine group, the mean FAI in initial LAD of −70.37 ± 7.1 HU improved to −72.90 ± 6.2 HU, but without statistical significance (p = 0.82) and Control group −69,13 ± 7,7 HU to −71,73 ± 6,3 HU (p= 0,64). FAI RCA from − 67.69 ± 5.4 HU to −71.23 ± 4.7 HU, without significance (p = 0.10) in Colchicine group and – 65,48 ± 5,5 HU to −69,08 ± 7,8 HU (p = 0,19) in control group. Conclusion: To date, a total of 40 patients have been randomized. In this interim analysis, with 50% of the sample already undergoing control coronary CT angiography, no association was observed with the use of colchicine and improvement in coronary inflammation after 12 months of using the medication.

Experimental evidence on colchicine's mode of action in human carotid artery plaques

Abstract Background and aims Atherosclerosis driven by inflammation is a major cause of cardiovascular events. Recent clinical trials have demonstrated the therapeutic potential of anti-inflammatory treatments. Consequently, colchicine is recommended in current guidelines as a second-line therapy for secondary prevention, although the drug's mechanism of action is not fully understood. Methods To this end, we performed a multiomic study of the effect of colchicine on human carotid plaques. Sections from endarterectomy specimens were exposed ex vivo to colchicine at concentrations of 2 ng/ml and 10 ng/ml for 24 hours and compared with untreated segments of the same plaque. Changes in gene expression were analyzed by RNA sequencing, and plaque secretomes were subjected to proteomic analysis by mass spectrometry. In situ cell proliferation was examined histologically. Results Our data suggest that colchicine primarily suppresses neutrophil and platelet degranulation, collagen degradation, and macrophage proliferation in atheromatous plaques in a dose-dependent manner, while stimulating myofibroblast activation. Conclusion Our study demonstrates multifactorial pathways by which colchicine, the first anti-inflammatory drug recommended by cardiovascular guidelines, acts on human atherosclerotic lesions. Targeting neutrophil and platelet degranulation, collagen degradation and macrophage proliferation could provide significant therapeutic benefit in atherosclerotic cardiovascular disease without the adverse side effects of colchicine.

Colchicine in patients with coronary disease undergoing coronary artery bypass surgery: a meta-analysis of randomized controlled trials

Abstract Background Recent randomized evidence has shown that low dose colchicine lowers the risk of cardiovascular events in patients with chronic coronary artery disease (CAD). Colchicine has also been used in coronary artery bypass grafting (CABG) with individual studies suggesting protective effects for postoperative atrial fibrillation (POAF). We performed a meta-analysis of studies assessing the effect of colchicine on outcomes in CABG surgery. Purpose To determine the potential of colchicine for reducing post-operative atrial fibrillation or other adverse events in patients undergoing CABG. Methods We systematically searched three libraries (MEDLINE, Web of Science and The Cochrane Library) selecting all randomized control trials (RCT) including patients who underwent CABG and were randomized for pre- or perioperative administration of colchicine versus standard of care. Primary outcome was incidence of POAF. Inverse variance method (DerSimonian&Laird) and random effects model were performed. The leave-one-out analysis was carried out as a sensitivity analysis to address possible outliers. Results From 205 screened studies, five met the inclusion criteria and were selected. The data from 839 patients were included in the final analysis. Included studies were published between 2014 and 2022. The perioperative administration of colchicine was associated with reduction of POAF rates after CABG when compared to standard of care (relative risk; RR= 0.54, 95% confidence interval; CI, 0.40-0.73, p<0.01 – Fig. 1). The leave-one-out analysis confirmed the robustness of the analysis, with minimal variations of the confidence interval (Fig. 2). Conclusions This meta-analysis of randomized studies suggests that the perioperative administration of colchicine is associated with significant reduction of POAF rates after CABG.Forest plotLeave-one-out analysis

Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.

Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients. We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5mg colchicine twice daily for 3months. The soluble suppressor of tumorigenicity (sST2), interleukin-1β, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3months. No significant effects were reported for colchicine on sST2, interleukin-1β levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P= .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P= .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R= .459, P< .001) at the end of follow-up. Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI. NCT06054100.

TCT-178 Effect of Colchicine on the Cardiovascular Outcomes in Patients With Acute Coronary Syndromes

TCT-178 Effect of Colchicine on the Cardiovascular Outcomes in Patients With Acute Coronary Syndromes

Colchicine Prevents Cardiac Rupture in Mice with Myocardial Infarction by Inhibiting P53-Dependent Apoptosis.

Cardiac rupture is a fatal complication following myocardial infarction (MI) and there are currently no effective pharmacological strategies for preventing this condition. In this study, we investigated the effect of colchicine on post-infarct cardiac rupture in mice and its underlying mechanisms.We induced MI in mice by permanently ligating the left anterior descending artery. Oral colchicine or vehicle was administered at a dose of 0.1 mg/kg/day from day 1 to day 7 after MI. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with colchicine.Colchicine significantly improved the survival rate (colchicine, n = 46: 82.6% versus vehicle, n = 42: 61.9%, P < 0.05) at 1 week after MI. Histological analysis revealed colchicine significantly reduced the infarct size and the number of macrophages around the infarct area. Colchicine decreased apoptosis in the myocardium of the border zone and cultured cardiomyocytes and fibroblasts as assessed by TUNEL assay. Colchicine also attenuated the activation of p53 and decreased the expression of cleaved-caspase 3 and bax, as assessed by Western blotting.Colchicine prevents cardiac rupture via inhibition of apoptosis, which is attributable to the downregulation of p53 activity. Our findings suggest that colchicine may be a prospective preventive medicine for cardiac rupture, however, large clinical trials are required.

Effect of Colchicine and Bio-catharantin on the DNA Relative Content and Stomatal Structure of Black Rice (Oryza sativa L. var. Jeliteng)

&lt;p&gt;Black rice (&lt;em&gt;Oryza sativa&lt;/em&gt; L. var. Jeliteng), known for its health benefits compared to white rice, faces challenges in productivity. Among varieties, this black rice is popular in Indonesia but shows low yield. Research on improving black rice through genetic manipulation with antimitotic substances is limited. Therefore, this study aims to compare the effects of colchicine and Bio-catharantin on the germination rate, DNA relative content, and stomatal structure of &lt;em&gt;O. sativa &lt;/em&gt;L. var. Jeliteng. Seeds were treated with colchicine (0.1%, 0.2%, and 0.3%) and Bio-catharantin (0.1%, 0.2%, 0.3%, 0.4%, and 0.5%) at soaking durations of 12, 24, and 48 hours. Germination was assayed, ploidy was determined using flow cytometry, and stomatal traits, including size and density, were examined microscopically. The results showed that Bio-catharantin did not exhibit any toxic effects on germination rates, whereas colchicine reduced germination starting at 0.2% concentration. Both chemical agents modified the DNA relative content of Jeliteng black rice. Colchicine generally increased stomatal length and width while decreasing stomatal density, with significant changes at 0.3% concentration for 24 hours. Bio-catharantin also altered stomatal traits, enhancing length and width in most cases but significantly reducing density under certain conditions. Bio-catharantin emerged as a promising alternative to colchicine for inducing chromosomal mutations in plants, offering benefits in altered stomatal structures without the toxic effects on germination, compared to colchicine.&lt;/p&gt;

Features of diagnostics and therapy of familial Mediterranean fever

The purpose of this work is to attempt to provide an overview of current recommendations for the diagnosis and treatment of familial Mediterranean fever, as well as to present our own clinical observation of this pathology. A selective analysis of the literature over the past 5 years (2020-2024) was carried out in the scientometric databases PubMed (https://pubmed.ncbi.nlm.nih.gov) and the Russian Science Citation Index (www.elibrary.ru). Current data on the autoinflammatory disease familial Mediterranean fever are reviewed. It is important to understand the fact that this pathological condition can be combined with a wide range of autoimmune diseases. The lack of therapy is dangerous for the development of serious complications (systemic amyloidosis). Attention is drawn to the use of colchicine, as well as in the case of colchicine resistance and insufficient effectiveness of colchicine – IL-1 inhibitors. We present our own clinical observation of this disease with an emphasis on the features of the course and stages of therapy for this pathology. A young man, Armenian, was treated for 3 years due to acute conditions with an increase in body temperature to febrile levels, severe abdominal pain and moderate arthralgia. The conditions were accompanied by leukocytosis and increased CRP, but no signs of acute surgical disease were detected. After a molecular genetic study, the diagnosis of familial Mediterranean fever was verified. Colchicine was prescribed, which helped stop many manifestations of the disease; she has been taking it regularly for 5 years. Currently, episodes of exacerbations have become significantly less frequent, laboratory markers of acute inflammation have normalized, but the use of colchicine in the maximum daily dose causes abdominal discomfort. Rare episodes of exacerbations during treatment suggest insufficient effectiveness of this drug. An option to achieve results in such a situation is to use a class of genetically engineered biological drugs such as IL-1 inhibitors. Familial Mediterranean fever is a rare pathological condition, but doctors of various clinical specialties should be wary of its detection. Achieving treatment success requires constant monitoring of the patient’s condition, prescribing therapy with colchicine or IL-1 inhibitors from the moment of diagnosis.

Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial.

Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] μm versus 87.2 [95% CI, 69.9 to 104.5] μm; difference, 34.2 [95% CI, 9.7 to 58.6] μm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.

Exploration of the regional effects of colchicine in the LoDoCo2 trial

The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.51; 95% CI 0.39-0.67 vs The Netherlands: HR 0.92; 95% CI 0.71-1.20). The aim of this study was to explore possible explanations for the apparent difference in magnitude of treatment effect of colchicine by region in the LoDoCo2 trial. The analysis explored potential determinants of variations in the magnitude of effectiveness of colchicine treatment across the regions. This included investigating differences in investigational product, clinical characteristics, concurrent medical therapies and the duration of follow-up using a range of statistical techniques, including sub-group, landmark and effect modification analyses. No differences were found in the colchicine product used in each region. Despite minor differences observed in baseline clinical characteristics and concomitant therapies, the effect modifier analyses demonstrated that these factors did not explain the difference in magnitude of treatment effect of colchicine by region. Randomization in Australia began more than 2 years before The Netherlands, with shorter duration of follow-up in The Netherlands compared to Australia. In a landmark analysis, over the period when more than 90% of patients in each region had been followed, the effects of colchicine were similar (Australia hazard ratio [HR] 0.58; 95% CI 0.34-0.97 vs The Netherlands HR 0.67; 95% CI 0.47-0.96). After examining several plausible explanations for the observed differences in the magnitude of treatment effect of colchicine between regions in the LoDoCo2 trial could be due to the differences in duration of follow-up but a substantial portion of the differences remain unexplained. https://www.anzctr.org.au/ACTRN12614000093684.

Effect of Colchicine for Prevention of Recurrent Stroke in Ischemic Stroke Patients with Atrial Fibrillation: A Randomized Double-blinded Placebo-- controlled Trial

Background: It has been proposed that colchicine may have the potential to prevent cardiovascular and cerebrovascular dysfunctions. Objective: This study evaluated the impact of colchicine on preventing recurrent stroke in patients with both ischemic stroke (IS) and atrial fibrillation (AF). Methods: A randomized, double-blinded, placebo-controlled trial was conducted at Golestan Hospital (Ahvaz, Iran) over one year, involving IS patients with AF. Demographic and clinical data were collected from the participants, who were then assigned to either the intervention or placebo groups. The experimental group was administered colchicine at a dosage of 0.05 mg twice daily for one year, while the control group received a placebo at a comparable dosage over the same timeframe. Results: In one year, 108 patients completed the study. There were 55 patients in the intervention group and 53 patients in the placebo group. During the second trimester of the trial, three patients in the colchicine group and 10 patients in the placebo group experienced recurrent strokes. Gastrointestinal issues were the most commonly reported complications (33 cases), followed by myalgia (8 patients). There were significant differences in the frequency of recurrent stroke and serum levels of C-reactive protein (CRP) between the colchicine and placebo groups (P &lt; 0.05) after intervention. Conclusion: In this study, colchicine was effective in reducing recurrent stroke and CRP levels in IS patients with AF compared to the control group. Further randomized controlled trials with larger sample sizes and extended durations are recommended to validate the results of this trial.

Effectiveness of Colchicine in Inducing Polyploidy in 'Balady' Mandarin

Effectiveness of Colchicine in Inducing Polyploidy in 'Balady' Mandarin

Recent advancements in targeting the immune system to treat hypertension

Hypertension is the key leading risk factor for death globally, affecting ∼1.3 billion adults, particularly in low- and middle-income countries. Most people living with hypertension have uncontrolled high blood pressure, increasing their likelihood of cardiovascular events. Significant issues preventing blood pressure control include lack of diagnosis, treatment, and response to existing therapy. For example, monotherapy and combination therapy are often unable to lower blood pressure to target levels. New therapies are urgently required to tackle this issue, particularly those that target the mechanisms behind hypertension instead of treating its symptoms. Acting via an increase in systemic and tissue-specific inflammation, the immune system is a critical contributor to blood pressure regulation and is considered an early mechanism leading to hypertension development. Here, we review the immune system's role in hypertension, evaluate clinical trials that target inflammation, and discuss knowledge gaps in pre-clinical and clinical data. We examine the effects of anti-inflammatory drugs colchicine and methotrexate on hypertension and evaluate the blockade of pro-inflammatory cytokines IL-1β and TNF-α on blood pressure in clinical trials. Lastly, we highlight how we can move forward to target specific components of the immune system to lower blood pressure. This includes targeting isolevuglandins, which accumulate in dendritic cells to promote T cell activation and cytokine production in salt-induced hypertension. We discuss the potential of the dietary fibre-derived metabolites short-chain fatty acids, which have anti-inflammatory and blood pressure-lowering effects via the gut microbiome. This would limit adverse events, leading to improved medication adherence and better blood pressure control.

Citrinin disrupts microtubule assembly in cardiac cells: Impact on mitochondrial organization and function

Citrinin (CTN) is a mycotoxin commonly present in various foods and feeds worldwide, as well as dietary supplements in Asian countries, but the risks and cellular mechanisms associated with its cardiotoxicity remains unclear. In this study, RNA-seq analysis of CTN-treated H9c2 cardiac cells demonstrated significant perturbations in pathways related to microtubule cytoskeleton and mitochondrial network organization. CTN disrupted microtubule polymerization and downregulated mRNA levels of microtubule-assembling genes, Map2 and Tpx2, in H9c2 cardiac cells. Additionally, CTN interfered with the distribution of mitochondrial network along the microtubules, leading to the accumulation of dysfunctional mitochondria characterized by elevated superoxide levels and reduced membrane potential. This disruption also caused the buildup of lysosomes and ubiquitinated proteins, which hindered waste clearance in microtubule-disassembled H9c2 cells. Molecular docking analysis indicated that CTN could bind to the colchicine binding site on β-tubulin, thereby mimicking the microtubule-disrupting effect of colchicine. This study provides morphological, transcriptomic, and mechanistic evidence to elucidate the cardiotoxic mechanisms of CTN, which involve the dysregulated microtubule network, subsequent mitochondrial mislocalization, and impaired proteolysis of damaged proteins/organelles in cardiac cells. Our findings may enhance the fundamental understanding and facilitate future risk assessment of CTN.

Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionThe systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional...

Colchicine in Patients With Coronary Disease Who Underwent Coronary Artery Bypass Surgery: A Meta-Analysis of Randomized Controlled Trials

Recent randomized evidence has shown that low-dose colchicine lowers the risk of cardiovascular events in patients with chronic coronary artery disease. Colchicine has also been used in coronary artery bypass grafting (CABG), with individual studies suggesting protective effects for postoperative atrial fibrillation (POAF). We performed a meta-analysis of studies assessing the effect of colchicine on outcomes in CABG surgery. We systematically searched 3 libraries (MEDLINE, Web of Science, and the Cochrane Library), selecting all randomized control trials including patients who underwent CABG and were randomized for perioperative administration of colchicine versus standard of care. The primary outcome was incidence of POAF. The inverse variance method (DerSimonian&Laird) and random-effects model were performed. The leave-one-out analysis was carried out as a sensitivity analysis to address possible outliers. From 205 screened studies, 5 met the inclusion criteria and were selected. The data from 839 patients were included in the final analysis. The included studies were published between 2014 and 2022. The perioperative administration of colchicine was associated with the reduction of POAF rates after CABG compared with standard of care (relative risk 0.54, 95% confidence interval 0.40 to 0.73, p <0.01). The leave-one-out analysis confirmed the robustness of the analysis, with minimal variations of the confidence interval. This meta-analysis of randomized studies suggests that the perioperative administration of colchicine is associated with significant reduction of POAF after CABG.