The Role of Galectin-3 in Heart Failure-The Diagnostic, Prognostic and Therapeutic Potential-Where Do We Stand?

Heart failure (HF) is a clinical syndrome with high morbidity and mortality, and its prevalence is rapidly increasing. Galectin-3 (Gal-3) is an important factor in the pathophysiology of HF, mainly due to its role in cardiac fibrosis, inflammation, and ventricular remodeling. Fibrosis is a hallmark of cardiac remodeling, HF, and atrial fibrillation development. This review aims to explore the involvement of Gal-3 in HF and its role in the pathogenesis and clinical diagnostic and prognostic significance. We report data on Gal-3 structure and molecular mechanisms of biological function crucial for HF development. Over the last decade, numerous studies have shown an association between echocardiographic and CMR biomarkers in HF and Gal-3 serum concentration. We discuss facts and concerns about Gal-3's utility in acute and chronic HF with preserved and reduced ejection fraction for diagnosis, prognosis, and risk stratification. Finally, we present attempts to use Gal-3 as a therapeutic target in HF.

Involvement of circRNAs in the Development of Heart Failure.

In recent years, interest in non-coding RNAs as important physiological regulators has grown significantly. Their participation in the pathophysiology of cardiovascular diseases is extremely important. Circular RNA (circRNA) has been shown to be important in the development of heart failure. CircRNA is a closed circular structure of non-coding RNA fragments. They are formed in the nucleus, from where they are transported to the cytoplasm in a still unclear mechanism. They are mainly located in the cytoplasm or contained in exosomes. CircRNA expression varies according to the type of tissue. In the brain, almost 12% of genes produce circRNA, while in the heart it is only 9%. Recent studies indicate a key role of circRNA in cardiomyocyte hypertrophy, fibrosis, autophagy and apoptosis. CircRNAs act mainly by interacting with miRNAs through a "sponge effect" mechanism. The involvement of circRNA in the development of heart failure leads to the suggestion that they may be promising biomarkers and useful targets in the treatment of cardiovascular diseases. In this review, we will provide a brief introduction to circRNA and up-to-date understanding of their role in the mechanisms leading to the development of heart failure.

Noninvasive assessment of left atrial fibrosis. Correlation between echocardiography, biomarkers, and electroanatomical mapping.

AIM: Left atrial (LA) fibrosis promotes atrial fibrillation (AF), may predict poor radiofrequency catheter ablation (RFCA) outcome, and may be assessed invasively using electroanatomical mapping (EAM). Speckle tracking echocardiography (STE) enables quantitative assessment of LA function. The aim was to assess the relationship between LA fibrosis derived from EAM and LA echocardiographic parameters as well as biomarkers of fibrosis in patients with AF. METHODS: Sixty-six patients (64% males, mean age 56 ± 10) with nonvalvular AF treated with first RFCA were prospectively studied. Seventy-three percent of patients were in sinus rhythm at the time of examination. LA geometry, systolic, and diastolic function were assessed. In STE global, peak atrial longitudinal (PALS) and contractile (PACS) strain were calculated. LA stiffness index (LAs) - the ratio of E/e' to PALS - was assessed. The EAM of LA was build using Carto System before RFCA. Low amplitude potentials area (LAPA) was quantitatively analyzed and expressed as a percentage of LA surface using the cut-off <0.5 mV to detect potential sites of fibrosis. The serum concentrations of MMP-9, PIIINP, and TGFß1were estimated before RFCA. RESULTS: Pearson correlation analysis showed a significant correlation between LA diastolic function parameters: PALS (-0.54, P < .001), LAs (0.65, P < .001), and LAPA in patients who were in sinus rhythm. Also LA volume significantly correlated with LAPA (0.44, P < .002). None of biomarkers correlated with LAPA. CONCLUSION: Left atrial diastolic parameters derived from STE correlate well with the extent of LA fibrosis. Thus, STE may be useful in the noninvasive assessment of LA fibrosis and selection of candidates for RFCA.

Long COVID and its cardiovascular consequences: What is known?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

2024 Guidelines of the Polish Society of Laboratory Diagnostics and the Polish Lipid Association on laboratory diagnostics of lipid metabolism disorders.

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area - the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

An update on cardiovascular disorders in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex multifactorial etiology that develops as a result of autoimmune processes, leading to widespread inflammation and malfunction of multiple tissues and organs, and, as a consequence, triggers arterial hypertension, conduction disorders, valvular heart disease, pulmonary hypertension (PH), and venous thromboembolism events (VTE), contributing to increased mortality. Moreover, autoimmune abnormalities can accelerate atherogenesis and lead to many SLE manifestations, including coronary artery disease (CAD) and cerebrovascular events. The current review aimed to systematize existing data from the latest works and summarize published guidelines and recommendations. In particular, the prevalence of cardiovascular disorders in SLE patients, advances in diagnostics (including imaging methods and biomarker laboratory testing), the possible future direction of therapy, and the latest European Alliance of Associations for Rheumatology (EULAR) guidelines for optimal management of cardiovascular risk in SLE were overviewed.

Prognostic Implications of Immature Platelet Fraction at 5-Year Follow-up Among ACS Patients Treated With Dual Antiplatelet Therapy.

Objective: Platelets are strongly associated with cardiovascular events due to their role in thrombotic processes. Reticulated platelets have higher prothrombotic potential. The aim of the study was to evaluate the effectiveness of immature platelet fraction (IPF) in predicting long-term clinical outcomes in patients with acute coronary syndrome (ACS). Methods: This prospective, observational study enrolled patients with ACS treated with dual antiplatelet therapy comprising acetylsalicylic acid and clopidogrel or ticagrelor. The primary outcome was a composite endpoint defined as major adverse cardiovascular events (MACE): all-cause death, myocardial infarction (MI), ischemic stroke, or unplanned revascularization. IPF was determined using flow cytometry in the first 24 h of hospitalization. MACE were evaluated by 2 physicians based on electronic databases and source documentation including discharge letters received from patients upon telephone contact. Results: Overall, there were 140 ACS patients (mean age 65.1 ± 11.7, 37 females [26.4%]) included in this study. Of them, 22.9% had diabetes mellitus, 69.3% hyperlipidemia, 25% had a history of MI. The median IPF values were 2.85 [1.8-4.2] %. Clinical follow-up (median time: 57 months [interquartile range 55-59 months]) was available for 130 patients (92.9%). MACE occurred in 27 patients (20.8%). There were higher rates of MACE at higher IPF tertiles (3rd vs 1st tertile: HR = 5.341 95% CI: 1.546-18.454, P = .008). Cox regression analyses showed that IPF level was independently associated with MACE. Time-dependent receiver-operating characteristic curve analysis revealed area under the curve of 0.656 for 5-year outcome with an IPF cutoff point of 3.45% being 63.0% sensitive and 65.0% specific for MACE. Conclusions: The study showed IPF may be an independent predictor of long-term mortality and MACE (ClinicalTrials.gov number, NCT06177587).

The effects of statins on the mevalonic acid pathway in recombinant yeast strains expressing human HMG-CoA reductase.

BACKGROUND: The yeast Saccharomyces cerevisiae can be a useful model for studying cellular mechanisms related to sterol synthesis in humans due to the high similarity of the mevalonate pathway between these organisms. This metabolic pathway plays a key role in multiple cellular processes by synthesizing sterol and nonsterol isoprenoids. Statins are well-known inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the cholesterol synthesis pathway. However, the effects of statins extend beyond their cholesterol-lowering action, since inhibition of HMGR decreases the synthesis of all products downstream in the mevalonate pathway. Using transgenic yeast expressing human HMGR or either yeast HMGR isoenzyme we studied the effects of simvastatin, atorvastatin, fluvastatin and rosuvastatin on the cell metabolism. RESULTS: Statins decreased sterol pools, prominently reducing sterol precursors content while only moderately lowering ergosterol level. Expression of genes encoding enzymes involved in sterol biosynthesis was induced, while genes from nonsterol isoprenoid pathways, such as coenzyme Q and dolichol biosynthesis or protein prenylation, were diversely affected by statin treatment. Statins increased the level of human HMGR protein substantially and only slightly affected the levels of Rer2 and Coq3 proteins involved in non-sterol isoprenoid biosynthesis. CONCLUSION: Statins influence the sterol pool, gene expression and protein levels of enzymes from the sterol and nonsterol isoprenoid biosynthesis branches and this effect depends on the type of statin administered. Our model system is a cheap and convenient tool for characterizing individual statins or screening for novel ones, and could also be helpful in individualized selection of the most efficient HMGR inhibitors leading to the best response and minimizing serious side effects.

Ischaemia modified albumin in patients with acute coronary syndrome and negative cardiac troponin I.

BACKGROUND: Approximately 40-60% of patients with acute coronary syndrome (ACS) have normal cardiac troponin I (cTnI) concentrations on admission. Ischaemia modified albumin (IMA) has been suggested as a new biomarker of myocardial ischaemia. METHODS: A total of 43 patients presenting with symptoms suggestive of ACS but with normal (< 0.1 µg/L) cTnI concentrations and 45 healthy subjects were studied. The patients from the study group were divided into two groups: STEMI (n = 28) and NSTEMI (n = 15). All these patients were undergoing percutaneous coronary intervention (PCI) with stenting. The concentrations of cTnI, myoglobin and IMA were determined on admission and 4 h after PCI. RESULTS: Mean (SD) IMA concentrations were higher in patients with ACS (114.39 ± 25.18 U/ml) as compared to the control group (96.24 ± 6.28 U/ml, p < 0.005). IMA concentrations ≥ 104.0 U/ml demonstrated 72.1% sensitivity and 75.6% specificity for the diagnosis of ACS. The area under the receiver operator characteristic curve was 0.766 (95% CI 0.664-0.868) for ACS patients (NSTEMI + STEMI). In both groups increased median (IQR) cTnI concentration after PCI was observed (STEMI patients to 65.4 (10.9-106.9) µg/L and NSTEMI to 17.6 (0.77-84.0) µg/L). In contrast, no increase in IMA concentration was observed. CONCLUSIONS: IMA may be a useful biomarker for the identification of ACS patients presenting with typical acute chest pain and/or abnormal electrocardiograms but negative cTnI.

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y12 Inhibitors and Their Association with Platelet Function.

INTRODUCTION: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y12 inhibitors while assessing their association with platelet activity and turnover parameters. MATERIALS AND METHODS: We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups. RESULTS: Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from -1.43 to -1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF. CONCLUSIONS: The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587).

Immature platelet fraction and immature platelet count as novel biomarkers of elevated platelet reactivity in NSTE-ACS patients receiving dual antiplatelet therapy.

BACKGROUND: Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. OBJECTIVES: The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. MATERIAL AND METHODS: This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. RESULTS: A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. CONCLUSION: Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587).

Immature platelet fraction in cardiovascular diagnostics and antiplatelet therapy monitoring.

Immature platelet fraction (IPF), circulating platelets still containing RNA, can be easily calculated by automated flow cytometry, this makes them an accessible biomarker. Higher IPF concentrations were reported in patients with thrombocytopenia, patients who were smokers, and also those who were diabetics. Several studies have reported their diagnostic and prognostic importance in patients presenting with acute coronary syndromes, especially ST-segment elevation myocardial infarction, where increased IPF level is an independent predictor of cardiovascular death. In addition, higher IPF were reported in patients with inadequate response to either clopidogrel or prasugrel, suggesting their potential role in antiplatelet therapy monitoring. Their prognostic significance was also observed in both coronary artery disease and postcardiac surgery status, where their higher levels correlated with the risk of major adverse cardiac events. The current review aims to present the current evidence on diagnostic, prognostic and potentially therapeutic roles of IPF in cardiovascular medicine.

Mitochondrial Quality Control: the Role in Cardiac Injury.

The heart is a highly energy-dependent organ, and most of its energy is provided by mitochondrial oxidative phosphorylation. Therefore, maintaining a well-functioning mitochondrial population is of paramount importance for cardiac homeostasis, since damaged mitochondria produce less adenosine triphosphate (ATP) and generate higher amounts of reactive oxygen species (ROS). Mitochondrial dysfunction is associated with the development of many diseases, including cardiovascular disorders. In this article, we review the role of mitochondria as key determinants of acute myocardial ischemic/reperfusion injury (IRI) and also diabetic cardiomyopathy. The structure and function of mitochondria are regulated by the mitochondrial quality control (MQC) system. Mitochondrial quality control mechanisms involve a series of adaptive responses that preserve mitochondrial structure and function as well as ensure cardiomyocyte survival and cardiac function after injury. This review summarizes the basic mechanisms of MQC, including mitochondrial dynamics (fusion and fission), mitophagy and mitochondrial biogenesis. Mitochondrial dynamics are mainly controlled by the level of fission and fusion proteins and also by their post-translational modifications. In addition, this review aims to provide a contemporary view of the importance of miRNA molecules in the regulation of mitochondrial dynamics at the post-transcriptional level. Thus, miRNAs play an important role not only in the pathogenesis and prognosis of cardiac diseases, but can also be an important therapeutic target.

Circulating and Platelet MicroRNAs in Cardiovascular Risk Assessment and Antiplatelet Therapy Monitoring.

Micro-ribonucleic acids (microRNAs) are small molecules that take part in the regulation of gene expression. Their function has been extensively investigated in cardiovascular diseases (CVD). Most recently, miRNA expression levels have been suggested as potential biomarkers of platelet reactivity or response to antiplatelet therapy and tools for risk stratification for recurrence of ischemic evens. Among these, miR-126 and miR-223 have been found to be of particular interest. Despite numerous studies aimed at understanding the prognostic value of miRNA levels, no final conclusions have been drawn thus far regarding their utility in clinical practice. The aim of this review is to critically appraise the evidence on the association between miRNA expression, cardiovascular risk and on-treatment platelet reactivity as well as provide insights on future developments in the field.

Application of Priming Strategy for Enhanced Paclitaxel Biosynthesis in Taxus × Media Hairy Root Cultures.

Despite huge progress in biotechnological approaches to paclitaxel production, Taxus spp. in vitro culture productivity still remains a challenge. This could be solved by developing a new strategy engaging mechanisms of the primed defence response joined with subsequent elicitation treatment to circumvent limitations in paclitaxel biosynthesis. The hairy roots were primed by preincubation with ß-aminobutyric acid (BABA) for 24 h or 1 week, and then elicited with methyl jasmonate (MeJA) or a mixture of MeJA, sodium nitroprusside and L-phenylalanine (MIX). The effect of priming was evaluated on a molecular level by examination of the expression profiles of the four genes involved in paclitaxel biosynthesis, i.e., TXS (taxadiene synthase), BAPT (baccatin III: 3-amino, 3-phenylpropanoyltransferase), DBTNBT (3'-N-debenzoyl-2-deoxytaxol-N-benzoyltransferase) and PAM (phenylalanine aminomutase), as well as rolC (cytokinin-ß-glucosidase), originated from the T-DNA of Agrobacterium rhizogenes. The maximum paclitaxel yield was achieved in cultures primed with BABA for 1 week and elicited with MIX (3179.9 ± 212 µg/g dry weight), which corresponded to the highest expression levels of TXS and BAPT genes. Although BABA itself induced the investigated gene expression over control level, it was not translated into paclitaxel production. Nevertheless, preincubation with BABA essentially affected paclitaxel yield, and the duration of BABA pretreatment seemed to have the most pronounced impact on its productivity.

Bovine corneal epithelial primary cultures as an in vitro model for ophthalmic drugs studies.

In the recent years a significant development of investigations with regard to bioavailability of ocular drugs has been noticed. The corneal epithelial barrier is the main pathway for ocular penetration of topically applied ophthalmic drugs into the anterior chamber. To work out an in vitro model of bovine corneal epithelial primary cultures and exercise it for permeability research with lipophilic and hydrophilic markers, permeability coefficients estimation of the 6-carboxyfluorescein and rhodamin B was made. The corneal epithelial cultures of the 3th or 4th passage were chosen for layered culture with inserts based on the liquid-liquid interface (for the first week) and the air-liquid interface (for the two following weeks). On the 7th, 12th, 18th, 21st experiment day TER values, and on the 21st day drug permeability coefficients, were determined. The mean TER values of the 7th, 12th, 18th, 21st day of corneal epithelial culture were: 122.14, 155.14, 198.43 and; 247.43 Wcm2, respectively. The mean values of permeability coefficients on the 21st day of culture for 6-carboxyfluorescein and rhodamin B were 3.87 +/-0.10 x 10(-6)cm/s and 3.65 +/- 0.06 x 10(-6)cm/s, respectively. We state that the in vitro bovine corneal epithelial primary culture model is useful for ocular studies.

A Review of the Molecular Mechanisms Underlying Cardiac Fibrosis and Atrial Fibrillation.

The cellular and molecular mechanism involved in the pathogenesis of atrial fibrosis are highly complex. We have reviewed the literature that covers the effectors, signal transduction and physiopathogenesis concerning extracellular matrix (ECM) dysregulation and atrial fibrosis in atrial fibrillation (AF). At the molecular level: angiotensin II, transforming growth factor-ß1, inflammation, and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodelling in AF. We conclude that the Ang-II-MAPK and TGF-ß1-Smad signalling pathways play a major, central role in regulating atrial fibrotic remodelling in AF. The above signalling pathways induce the expression of genes encoding profibrotic molecules (MMP, CTGF, TGF-ß1). An important mechanism is also the generation of reactive oxygen species. This pathway induced by the interaction of Ang II with the AT2R receptor and the activation of NADPH oxidase. Additionally, the interplay between cardiac MMPs and their endogenous tissue inhibitors of MMPs, is thought to be critical in atrial ECM metabolism and fibrosis. We also review recent evidence about the role of changes in the miRNAs expression in AF pathophysiology and their potential as therapeutic targets. Furthermore, keeping the balance between miRNA molecules exerting anti-/profibrotic effects is of key importance for the control of atrial fibrosis in AF.

The Diagnostic and Therapeutic Potential of Galectin-3 in Cardiovascular Diseases.

Galectin-3 plays a prominent role in chronic inflammation and has been implicated in the development of many disease conditions, including heart disease. Galectin-3, a regulatory protein, is elevated in both acute and chronic heart failure and is involved in the inflammatory pathway after injury leading to myocardial tissue remodelling. We discussed the potential utility of galectin-3 as a diagnostic and disease severity/prognostic biomarker in different cardio/cerebrovascular diseases, such as acute ischemic stroke, acute coronary syndromes, heart failure and arrhythmogenic cardiomyopathy. Over the last decade there has been a marked increase in the understanding the role of galectin-3 in myocardial fibrosis and inflammation and as a therapeutic target for the treatment of heart failure and myocardial infarction.

Prognostic value of galectin-3 and right ventricular function for long-term mortality in heart failure patients treated with cardiac resynchronization therapy.

Recently, associations between the biomarker galectin-3 and numerous pathological processes involved in heart failure (HF) and right ventricular (RV) function have been observed. We aimed to assess the long-term prognostic ability of galectin-3 and RV function parameters for all-cause mortality in HF patients treated with cardiac resynchronization therapy (CRT). We prospectively studied 63 symptomatic HF patients with a left ventricular (LV) ejection fraction (EF) ≤ 35%. The median serum galectin-3 concentration was 13.4 ng/mL (IQR 11.05, 17.15). A detailed assessment of LV and RV geometry and function was performed with echocardiography. CRT defibrillator implantation was achieved in all patients without major complications. The follow-up lasted 5 years. In the multivariable Cox regression model, independent predictors for all-cause mortality were log baseline galectin-3 and baseline RV function expressed as tricuspid annular plane systolic excursion with HR 2.96 (p = 0.037) and HR 0.88 (p = 0.023), respectively. Analysis of subgroups defined by galectin-3 concentration and CRT response showed that patients with high baseline galectin-3 concentrations and a lack of response to CRT had a significantly lower probability of survival. In our patient cohort, the baseline galectin-3 concentration and RV function were independent predictors of long-term all-cause mortality in HFrEF patients following CRT implantation.

Molecular mechanisms of organ damage in sepsis: an overview.

Sepsis is one of the most common reasons for hospitalization. This condition is characterized by systemic inflammatory response to infection. International definition of sepsis mainly points out a multi-organ dysfunction caused by a deregulated host response to infection. An uncontrolled inflammatory response, often referred to as "cytokine storm", leads to an increase in oxidative stress as a result of the inhibition of cellular antioxidant systems. Oxidative stress, as well as pro-inflammatory cytokines, initiate vascular endothelial dysfunction and, in consequence, impair microcirculation. Microcirculation damage leads to adaptive modifications of cell metabolism. Moreover, mitochondrial dysfunction takes place which results in increased apoptosis and organ damage. Non-coding RNA fragments, especially miRNA molecules, may play an important role in the pathomechanism of sepsis. Numerous studies have indicated altered expression of various miRNAs in sepsis. miRNAs can be used as markers in the diagnosis and prognosis of disease development. In turn, intracellular miRNAs regulate the TLR4/NFκB pathway responsible for the expression of pro-inflammatory cytokine genes involved in the inflammatory response in sepsis. The understanding of detailed molecular mechanisms leading to organ damage can contribute to the development of specific therapy methods thereby improving the prognosis of patients with sepsis.