Cardiospecific Troponins as Laboratory Biomarkers of Myocardial Cell Injury in Hypertension: A Mini-Review.

To date, it is well known that a significant number of diseases of cardiovascular genesis (coronary heart disease, myocardial infarction, cardiomyopathy, Takotsubo syndrome, heart failure, etc.) and extra-cardiac genesis (renal failure, chronic obstructive pulmonary disease, sepsis, diabetes mellitus, etc.) cause injury to contractile cells of the heart muscle (myocardial cells). The most sensitive and specific criteria for proving myocardial cell injury are cardiospecific troponins (CSTns) - CSTnI and CSTnT. According to the current clinical recommendations of the European, American, and Russian Cardiological Communities, CSTnI and CSTnT are the main biomarkers for early diagnosis of myocardial infarction. Hypertension is one of the most dangerous and common risk factors for the development of cardiovascular pathologies and is associated with a high risk of dangerous cardiovascular complications. Therefore, there is an urgent need to search for new biomarkers for the timely assessment of the prognosis of patients with hypertension. This mini-review aims to substantiate the possibilities of using the cardiomarkers (CSTnI and CSTnT) to assess the prognosis of patients suffering from hypertension and to discuss potential mechanisms that cause injury to myocardial cells and increase serum levels of CSTnI and CSTnT. This is a narrative mini-review, which was prepared using the following databases: Pubmed/Medline, PubMed Central, Embase, Scopus, and Web of Science. The following keywords were used in the literature search: "myocardial cells", "injury", "damage", and "hypertension" in combination with the terms "mechanisms of injury" "predictive significance", "cardiac troponins", or "cardiospecific troponins".

The Essential Strategies to Mitigate Cardiotoxicity Caused by Doxorubicin.

The study of mechanisms underlying cardiotoxicity of doxorubicin and the development of strategies to mitigate doxorubicin-induced cardiotoxicity are the most relevant issues of modern cardio-oncology. This is due to the high prevalence of cancer in the population and the need for frequent use of highly effective chemotherapeutic agents, in particular anthracyclines, for optimal management of cancer patients. However, while being a potent agent to counteract cancer, doxorubicin also affects the cardiovascular systems of patients undergoing chemotherapy in a significant and unfavorable fashion. Consecutively reviewed in this article are risk factors and mechanisms of doxorubicin cardiotoxicity, and the essential strategies to mitigate cardiotoxic effects of doxorubicin treatment in cancer patients are discussed.

The negative effects of statin drugs on cardiomyocytes: current review of laboratory and experimental data (mini-review).

Statin drugs have long been used as a key component of lipid-lowering therapy, which is necessary for the prevention and treatment of atherosclerosis and cardiovascular diseases. Many studies focus on finding and refining new effects of statin drugs. In addition to the main lipid-lowering effect (blocking cholesterol synthesis), statin drugs have a number of pleiotropic effects, including negative effects. The main beneficial effects of statin drugs on the components of the cardiovascular system are: anti-ischemic, antithrombotic, anti-apoptotic, antioxidant, endothelioprotective, anti-inflammatory properties, and a number of other beneficial effects. Due to these effects, statin drugs are considered one of the main therapeutic agents for the management of patients with cardiovascular pathologies. To date, many review manuscripts have been published on the myotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and diabetogenic effects of statins. However, there are no review manuscripts considering the negative effect of statin drugs on myocardial contractile cells (cardiomyocytes). The purpose of this review is to discuss the negative effects of statin drugs on cardiomyocytes. Special attention is paid to the cardiotoxic action of statin drugs on cardiomyocytes and the mechanisms of increased serum levels of cardiac troponins. In the process of preparing this review, a detailed analysis of laboratory and experimental data devoted to the study of the negative effects of statin drugs on cardiomyocytes was carried out. The literature search was carried out with the keywords: statin drugs, negative effects, mechanisms, cardiac troponins, oxidative stress, apoptosis. Thus, statin drugs can have a number of negative effects on cardiomyocytes, in particular, increased oxidative stress, endoplasmic reticulum stress, damage to mitochondria and intercalated discs, and inhibition of glucose transport into cardiomyocytes. Additional studies are needed to confirm and clarify the mechanisms and clinical consequences of the negative effects of statin drugs on cardiomyocytes.

Gender Specificities of Cardiac Troponin Serum Levels: From Formation Mechanisms to the Diagnostic Role in Case of Acute Coronary Syndrome.

Cardiac troponins T and I are the main (most sensitive and specific) laboratory indicators of myocardial cell damage. A combination of laboratory signs of myocardial cell damage (elevated levels of cardiac troponins T and I) with clinical (severe chest pain spreading to the left side of the human body) and functional (rise or depression of the ST segment, negative T wave or emergence of the Q wave according to electrocardiography and/or decrease in the contractility of myocardial areas exposed to ischemia according to echocardiography) signs of myocardial ischemia is indicative of the ischemic damage to cardiomyocytes, which is characteristic of the development of acute coronary syndrome (ACS). Today, with early diagnostic algorithms for ACS, doctors rely on the threshold levels of cardiac troponins (99th percentile) and on the dynamic changes in the serum levels over several hours (one, two, or three) from the moment of admission to the emergency department. That said, some recently approved highly sensitive methods for determining troponins T and I show variations in 99th percentile reference levels, depending on gender. To date, there are conflicting data on the role of gender specificities in the serum levels of cardiac troponins T and I in the diagnostics of ACS, and the specific mechanisms for the formation of gender differences in the serum levels of cardiac troponins T and I are unknown. The purpose of this article is to analyze the role of gender specificities in cardiac troponins T and I in the diagnostics of ACS, and to suggest the most likely mechanisms for the formation of differences in the serum levels of cardiac troponins in men and women.

Modern Concepts of the Role of Fine Particles (PM 2.5) in the Genesis of Atherosclerosis and Myocardial Damage: Clinical and Epidemiological Data, the Main Pathophysiological Mechanisms.

Due to the fact that atherosclerotic cardiovascular diseases (CVDs) dominate in the structure of morbidity, disability and mortality of the population, the study of the risk factors for the development of atherosclerotic CVDs, as well as the study of the underlying pathogenetic mechanisms thereof, is the most important area of scientific research in modern medicine. Understanding these aspects will allow improving the set of treatment and preventive measures and activities. One of the important risk factors for the development of atherosclerosis, which has been actively studied recently, is air pollution with fine particulate matter (PM 2.5). According to clinical and epidemiological data, the level of air pollution with PM 2.5 exceeds the normative indicators in most regions of the world and is associated with subclinical markers of atherosclerosis and mortality from atherosclerotic CVDs. The aim of this article is to systematize and discuss in detail the role of PM 2.5 in the development of atherosclerosis and myocardial damage with the consideration of epidemiological and pathogenetic aspects. Materials and Methods: This narrative review is based on the analysis of publications in the Medline, PubMed, and Embase databases. The terms "fine particles" and "PM 2.5" in combination with "pathophysiological mechanisms," "cardiovascular diseases", "atherosclerosis", "cardiac troponins", "myocardial damage" and "myocardial injury" were used to search publications. Conclusion: According to the conducted narrative review, PM 2.5 should be regarded as the significant risk factor for the development of atherosclerotic CVDs. The pro-atherogenic effect of fine particulate matter is based on several fundamental and closely interrelated pathophysiological mechanisms: endothelial dysfunction, impaired lipid metabolism, increased oxidative stress and inflammatory reactions, impaired functioning of the vegetative nervous system and increased activity of the hemostatic system. In addition, PM 2.5 causes subclinical damage to cardiac muscle cells by several mechanisms: apoptosis, oxidative stress, decreased oxygen delivery due to coronary atherosclerosis and ischemic damage of cardiomyocytes. Highly sensitive cardiac troponins are promising markers for detecting subclinical myocardial damage in people living in polluted regions.

Hypertension as One of the Main Non-Myocardial Infarction-Related Causes of Increased Cardiospecific Troponins: From Mechanisms to Significance in Current Medical Practice.

It is well known that many pathological conditions of both cardiovascular diseases (CVDs) (coronary heart disease, myocardial infarction, arrhythmias, myocarditis, cardiomyopathy, etc.) and non-cardiac (sepsis, anemia, kidney diseases, diabetes mellitus, etc.) origin in the course of their development cause injury to contractile cardiac muscle cells - myocardial cells (MCs). One of the most sensitive and specific criteria for detecting MC injury are cardiospecific troponins (CTs), which are regulatory protein molecules that are released into the blood serum from MC upon their death or injury. Current methods for determining CTs are called high-sensitive ones, and their main advantage is a very low minimum detectable concentration (limit of detection) (average 1 - 10 ng/L or less), which allows early detection of minor MC injury at the earliest stages of CVDs, and therefore they can change the understanding of disease development mechanisms and open up new diagnostic possibilities. One of the most common and dangerous early diseases of the cardiovascular system is hypertension (HT). The novelty of this article lies in the discussion of a new diagnostic direction - predicting the risk of developing CVDs and their dangerous complications in patients with HT by determining the concentration of CTs. In addition, pathophysiological mechanisms underlying MC injury and the release of CTs into the bloodstream and the elimination of CTs into the urine are proposed. This information will contribute to additional fundamental and clinical research to verify the new diagnostic possibility of using CTs in clinical practice (for the management of patients with HT).

The Role of Fine Particles (PM 2.5) in the Genesis of Atherosclerosis and Myocardial Damage: Emphasis on Clinical and Epidemiological Data, and Pathophysiological Mechanisms.

Due to the fact that atherosclerotic cardiovascular diseases (CVDs) dominate in the structure of morbidity, disability and mortality of the population, the study of the risk factors for the development of atherosclerotic CVDs, as well as the study of the underlying pathogenetic mechanisms thereof, is the most important area of scientific research in modern medicine. Understanding these aspects will allow to improve the set of treatment and preventive measures and activities. One of the important risk factors for the development of atherosclerosis, which has been actively studied recently, is air pollution with fine particulate matter (PM 2.5). According to clinical and epidemiological data, the level of air pollution with PM 2.5 exceeds the normative indicators in most regions of the world and is associated with subclinical markers of atherosclerosis and mortality from atherosclerotic CVDs. The aim of this article is to systematize and discuss in detail the role of PM 2.5 in the development of atherosclerosis and myocardial damage.

The Metabolic Pathway of Cardiac Troponins Release: Mechanisms and Diagnostic Role.

Modern methods of cardiac troponin determination have enabled early diagnosis of acute myocardial infarction (AMI) and selection of optimal treatment tactics for patients early from admission. It has markedly improved the further prognosis of these patients. Unfortunately, there are a number of problems arising from the use of high-sensitivity cardiac troponins: frequent and unexplained increases in serum troponin levels in a number of pathological conditions not associated with AMI; insufficient study of mechanisms of release and increase, features of circulation and elimination of cardiac troponins; inconsistent data on the influence of several factors (circadian, gender and age characteristics), on cardiac troponin levels. All this may be accompanied by difficulties and errors in differential diagnosis as well as insufficient use of the diagnostic potential of cardiac troponins. In general, these problems are due to our insufficient understanding of the metabolic pathway of cardiac troponins. This review briefly discusses the main stages of the metabolic pathway of cardiac troponins and focuses in detail on the first stage of metabolism (the release of cardiac troponins).

Cardiac Troponins as Biomarkers of Cardiac Myocytes Damage in Case of Arterial Hypertension: From Pathological Mechanisms to Predictive Significance.

BACKGROUND: Many pathological conditions of both cardiovascular and non-cardiac origin in the course of their development cause damage to contractile cardiac muscle cells-cardiac myocytes (CMCs). One of the most sensitive and specific criteria for detecting CMCs are cardiac troponins (CTs), which are regulatory protein molecules that are released into the blood serum from CMCs upon their death or damage. New (high-sensitive) methods for detecting CTs allow the detection of minor CMCs damages at the earliest stages of cardiovascular diseases and can therefore change the understanding of disease development mechanisms and open up new diagnostic possibilities. One of the most common and dangerous early diseases of the cardiovascular system is arterial hypertension. The purpose of this paper is to summarize the pathophysiological mechanisms underlying CMCs damage and CTs release into the bloodstream in the case of arterial hypertension and to state the clinical significance of increased CTs levels in patients with arterial hypertension. MATERIALS AND METHODS: This is a descriptive review, which was prepared using the following databases: Embase, Pubmed/Medline and Web of Science. The following key words were used in the literature search: "myocardial injury" and "arterial hypertension" in combination with the terms "cardiac troponins" and "mechanisms of increase". CONCLUSIONS: According to a literature analysis, CMCs damage and CTs release in the case of arterial hypertension occur according to the following pathophysiological mechanisms: myocardial hypertrophy, CMCs apoptosis, damage to the CMC cell membrane and increase in its permeability for CTs molecules, as well as changes in the glomerular filtration rate. Most often, increased CTs serum levels in case of arterial hypertension indicate an unfavorable prognosis. Data on the CTs predictive significance in case of arterial hypertension open the prospects for the use of these biomarkers in the choice of patient management plans.

On the Effect of Heterophilic Antibodies on Serum Levels of Cardiac Troponins: A Brief Descriptive Review.

Serum levels of cardiac troponins can be increased both with myocardial damage and in the absence of myocardial damage. In the second case, this is due to the influence of false-positive factors, among which heterophilic antibodies play a significant role. Understanding the causes of the formation of heterophilic antibodies, the features and mechanisms of their effect on serum levels of cardiac troponins, is an important condition for interpreting a false-positive result due to the influence of heterophilic antibodies. This brief, descriptive review presents the causes of heterophilic-antibodies formation and discusses their effect on serum levels of cardiac troponins.

Features of the Metabolisms of Cardiac Troponin Molecules-Part 1: The Main Stages of Metabolism, Release Stage.

Cardiac troponins (cTns) have long been the most valuable and specific biomarkers for detecting ischemic myocardial cells (MCs) injury, which is one of the key signs of myocardial infarction (MI). Modern methods (highly sensitive and ultra-sensitive immunoassays (hs-cTns)) of detection are an important and indispensable tool for the early diagnosis of MI and the choice of patient management protocols. Timely diagnosis of MI can significantly improve the prognosis of patients. However, in real clinical practice, doctors often face a significant problem when using cTns-the difficulty of differential diagnosis due to frequent and unexplained increases in the concentration of cTns in blood serum. In addition, there is conflicting information that may potentially affect the diagnostic capabilities and value of cTns: the influence of certain biological factors (diurnal rhythm, gender and age) on serum cTns levels; extra-cardiac expression of cTns; the possibilities of non-invasive diagnosis of MI; and other pathological conditions that cause non-ischemic injury to MCs. To solve these problems, it is necessary to concentrate on studying the metabolism of cTns. The review of our current knowledge about cTns metabolism consists of two parts. In this (first) part of the manuscript, the main stages of cTns metabolism are briefly described and the mechanisms of cTns release from MCs are considered in detail.

Some Common Causes of False Positive Increases in Serum Levels of Cardiac Troponins.

Cardiac troponin molecules (cTnI and cTnT) are the most valuable and in-demand biomarkers for detecting various types of myocardial damage (reversible and irreversible, ischemic, inflammatory, toxic, etc.) in current clinical practice. These biomarkers are widely used for early diagnosis of acute myocardial infarction (AMI) and risk stratification of patients suffering from a number of cardiac (such as myocarditis, heart failure, cardiomyopathy, etc.) and extra-cardiac diseases (such as sepsis, renal failure, pulmonary embolism, neurological pathologies, etc.) that negatively affect the cells of cardiac muscle tissue. However, in daily routine clinical activities, internists and cardiologists often encounter cases of false increases in the concentrations of cardiospecific troponins. A false increase in the concentration of troponins contributes to an incorrect diagnosis and incorrect therapy, which can harm the patient. A false increase in the concentration of troponins contributes to an incorrect diagnosis and incorrect therapy, which can harm the patient, therefore, internists and cardiologists should be well aware of the main reasons and mechanisms for false-positive results cTnI and cTnT. This review article mainly focuses on the causes of falsepositive increases in serum levels of cTnI and cTnT, which provide helpful clues for the accurate diagnosis of AMI and evidence for the differential diagnosis.

False-Positive Causes in Serum Cardiac Troponin Levels.

Cardiac troponins (cTns) are the most valuable and specific markers of cardiovascular diseases, including acute myocardial infarction. These biomarkers can also be used to assess the degree of myocardial damage in non-cardiac diseases that can negatively affect the cells of cardiac muscle tissue. However, in everyday clinical practice, doctors often encounter with false-positive cases of increased cTns. False-positive cases of increased cTns can contribute to incorrect diagnosis and subsequent inadequate treatment, which causes significant harm to the patient. This review discusses some common causes of a false-positive increase in the level of cTns in the blood serum. Such causes are fibrin clots, heterophilic antibodies, alkaline phosphatase, rheumatoid factor, and cross-reactions of diagnostic (anti-cTn) antibodies with skeletal troponins. Detailed attention is focused on the mechanisms of false-positive increase, and ways to identify and combat these false-positive causes of increased cTns. This has an important practical significance in modern clinical practice.