The place of beta-adrenergic receptor blockers in the treatment of arterial hypertension: from bench-to-bedside.

Arterial hypertension is a multifaceted condition influenced by numerous pathophysiological factors. The key contributors to its pathogenesis encompass an unhealthy lifestyle, dysregulation of the sympathetic nervous system, alterations in the activity of adrenergic receptors, disruptions in sodium metabolism, structural and functional abnormalities in the vascular bed, as well as endothelial dysfunction, low-grade inflammation, oxidative stress etc. Despite extensive research into the mechanisms of arterial hypertension development over the centuries, its pathogenesis remains incompletely understood, and the selection of an effective treatment strategy continues to pose a significant challenge. Arterial hypertension is characterized by a diminished sensitivity of the ß-adrenergic system, leading to the utilization of ß-adrenergic blockers and other antihypertensive drugs in its treatment. This review delves into the mechanisms of action of beta-adrenergic receptor blockers in the treatment of hypertension and their respective effects.

Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts.

Rheumatoid arthritis (RA) is an idiopathic, autoimmune connective tissue disorder that primarily affects the synovial joints, causing symmetric, erosive-deforming polyarthritis. It is also associated with extra-articular manifestations, particularly cardiovascular (CV) diseases (CVD). CV risk modification in RA remains unsolved despite recent advances in the management of RA. RA is an independent risk factor for atherosclerosis. RA and atherosclerosis share similar pathophysiological features (such as the pro-inflammatory cascade activation including interleukin-6) and risk factors (such as microflora dysbacteriosis and smoking). Patients with RA experience an exacerbation of atherogenesis, with atheromas destabilization, endothelial dysfunction, vasculitis, and hypercytokinemia. Consequently, the inflammatory response associated with RA is the basis for CVD development. The treat-to-target strategy not only improved RA control but also had a favorable effect on the morpho-functional state of the CV system in patients living with RA. Thus, disease-modifying antirheumatic drugs (DMARDs) - in particular methotrexate - may have a beneficial effect on the prevention of CV events in RA. It must be mentioned that RA is a serious multi-system disease, not only because of a window period during which the course of RA can be reversed, but also due to early damage to the heart and blood vessels. For this reason, a thorough cardiological assessment must be performed for all patients with RA, regardless of sex, age, disease stage, and disease activity score.

Diabetic Cardiomyopathy: 2023 Update by the International Multidisciplinary Board of Experts.

Diabetes mellitus (DM) is considered by many the pandemic of the 21st century and is associated with multiple organ damages. Among these, cardiovascular complications are responsible for an incredible burden of mortality and morbidity in Western Countries. The study of the pathological mechanisms responsible for the cardiovascular complications in DM patients is key for the development of new therapeutic strategies. The metabolic disorders caused by hyperglycemia, insulin resistance, and dyslipidemia, results in a cascade of pathomorphological changes favoring the atherosclerotic process and leading to myocardial remodeling. Parallel to this, oxidative stress, calcium overload, mitochondrial dysfunction, activation of protein kinase C signaling pathways, myocardial lipomatosis, and low-grade inflammation of the myocardium - are the main pathways responsible for the diabetic cardiomyopathy development. This review aims to appraise and discuss the pathogenetic mechanisms behind the diabetic cardiomyopathy development.

Melatonin mitigates oxidative damage induced by anthracycline: a systematic-review and meta-analysis of murine models.

Background: Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced cardiotoxicity. There is a strong clinical need for a molecule capable of effectively preventing and reducing the oxidative damage caused by ANT. In vitro and in vivo studies conducted in mice have shown that melatonin stimulates the expression of antioxidative agents and reduces lipid peroxidation induced by ANT. Methods: We investigated this issue through a meta-analysis of murine model studies. The outcome of the meta-analysis was to compare oxidative damage, estimated by products of lipid peroxidation (MDA = Malondialdehyde) and markers of oxidative stress (SOD = Superoxide Dismutase, GSH = Glutathione), along with a marker of cardiac damage (CK-MB = creatine kinase-myocardial band), assessed by measurements in heart and/or blood samples in mice undergoing ANT chemotherapy and assuming melatonin vs. controls. The PubMed, OVID-MEDLINE and Cochrane library databases were analysed to search English-language review papers published from the inception up to August 1st, 2023. Studies were identified by using Me-SH terms and crossing the following terms: "melatonin", "oxidative stress", "lipid peroxidation", "anthracycline", "cardiotoxicity". Results: The metanalysis included 153 mice administered melatonin before, during or immediately after ANT and 153 controls from 13 studies. Compared with controls, the levels of all oxidative stress markers were significantly better in the pooled melatonin group, with standardized mean differences (SMD) for MDA, GSH and SOD being -8.03 ± 1.2 (CI: -10.43/-5.64, p < 0.001), 7.95 ± 1.8 (CI: 4.41/11.5, p < 0.001) and 3.94 ± 1.6 (CI: 0.77/7.12, p = 0.015) respectively. Similarly, compared with controls, CK-MB levels reflecting myocardial damage were significantly lower in the pooled melatonin group, with an SMD of -4.90 ± 0.5 (CI: -5.82/-3.98, p < 0.001). Conclusion: Melatonin mitigates the oxidative damage induced by ANT in mouse model. High-quality human clinical studies are needed to further evaluate the use of melatonin as a preventative/treatment strategy for ANT-induced cardiotoxicity.

Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy.

RATIONALE: The global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy. OBJECTIVE: The redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis. METHODS: For this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed. RESULTS: For all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium. CONCLUSION: Dapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.

Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods.

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and is encoded by the LPA gene. The apo(a) is extremely heterogeneous in size due to the copy number variations in the kringle-IV type 2 (KIV2) domains. In this review, we aim to discuss the role of genetics in establishing Lp(a) as a risk factor for coronary heart disease (CHD) by examining a series of molecular biology techniques aimed at identifying the best strategy for a possible application in clinical research and practice, according to the current gold standard.

HIV-Related Atherosclerosis: State-of-the-Art-Review.

The infection caused by the Human Immunodeficiency Virus (HIV) has spread rapidly across the globe, assuming the characteristics of an epidemic in some regions. Thanks to the introduction of antiretroviral therapy into routine clinical practice, there was a considerable breakthrough in the treatment of HIV, that is now HIV is potentially well-controlled even in low-income countries. To date, HIV infection has moved from the group of life-threatening conditions to the group of chronic and well controlled ones and the quality of life and life expectancy of HIV+ people, with an undetectable viral load is closer to that of an HIV- people. However, unsolved issues still persist. For example: people living with HIV are more prone to the age-related diseases, especially atherosclerosis. For this reason, a better understanding of the mechanisms of HIV-associated destabilization of vascular homeostasis seems to be an urgent duty, that may lead to the development of new protocols, bringing the possibilities of pathogenetic therapies to a new level. The purpose of the article was to evaluate the pathological aspects of HIV-induced atherosclerosis.

Chemotherapy, hypothyroidism and oral dysbiosis as a novel risk factor of cardiovascular pathology development.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the population, as well as the economic burden of the health care system. Currently, CVDs account for more than 17.6 million deaths a year and are projected to exceed 23.6 million by 2030. Unstable atheroma, and its rupture, underlies the pathology of most cardiovascular complications, particularly acute coronary syndrome, mortality from which, compared with other CV events, remains the leading one. Despite numerous efforts by WHO, national health systems, and medical authorities, the incidence and mortality from cardiovascular events remain critically high. Thus, the search for new risk factors for the development of CV pathology looks very relevant. Our working group decided to amalgamate our research data, which reflects the study of modern risk factors from the Armenian, Russian, Georgian, and Iranian medical schools. In particular, the aspects of cardiotoxic effects of chemotherapy, hypothyroidism, and oral dysbiosis are discussed.

Cardiac Sarcoidosis: A Contemporary Concept of Forgotten Granulomatosis.

Sarcoidosis is a complex multisystem inflammatory granulomatous disease that can affect any organ, with a wide range of clinical presentations. A significant number of patients with systemic sarcoidosis may also have cardiac involvement. Clinical manifestations of cardiac sarcoidosis can include various rhythm and conduction disturbances, as well as heart failure. The structure of sarcoid granulomas is similar to that of tuberculous granulomas, but in contrast, they lack caseous necrosis. Tissue changes in sarcoidosis tissues depend on the stage of development of the disease, progressing from pathological process: macrophage-lymphocytic infiltration to epithelioid cell granuloma formation, and fibrosis. Granulomas can be found in any part of the myocardium, with the most common locations being the free wall of the left ventricle, the basal part of the interventricular septum, and the interatrial septum. Vasculopathy of the pulmonary circulation and coronary arteries is often observed. Advancements in diagnostic imaging techniques, such as computer tomography and magnetic resonance imaging, have facilitated the verification of cardiac sarcoidosis. This article presents an analysis of updated information on cardiac sarcoidosis by a multidisciplinary working group.

The Pathophysiological Basis of Diabetic Cardiomyopathy Development.

Diabetes mellitus (DM) provokes widely known structural and functional dyscoordination of the myocardium performance. A cascade of pathophysiological changes occurs due to metabolic disorders caused by hyperglycemia, insulin resistance, and dyslipidemia. Free fatty acids can stimulate oxidation and accumulate in the cytosol, leading to lipotoxic effects by forming ceramides, diacylglycerol, and reactive oxygen species (ROS). Hyperglycemia also causes an increase in the content of reactive oxygen species and the formation of advanced glycation end (AGE) products, which is accompanied by the development of cardiac glucotoxicity. The combination of these pathophysiological processes, ATP deficiency, and the development of myocardial fatty degeneration induce calcium stress, as well as dysfunction of mitochondria and endoplasmic reticulum, activation of signaling pathways of protein kinase C (PKC), mitogen-activated protein kinases (MAPK), etc., causing chronic sluggish inflammation, as well as first diastolic and further systolic dysfunction, and myocardial fibrosis. This article reviews the data on diabetic alteration of the cardiovascular system.

The Keystones of Right Ventricular Arrhythmogenic Cardiomyopathy-Induced Morphological Disarrangement.

Arrhythmogenic right ventricular cardiomyopathy is an urgent problem of modern cardiology. This myocardial remodeling manifests various desmosomopathies, channelopathies, and other mutations resulting in a violation of the coordinated heart work, particularly the myocardium. The incidence of this cardiomyopathy is not significant. Still, it is worth noting that athletes are at an increased risk of developing this disease, emphasizing the importance of studying this topic and its relevance from cardiologists and sports physicians. Moreover, the clinical pattern of this disease is heterogeneous. This pathology requires strengthening control and attention of medical personnel and constant improvement and optimization of diagnostic methods and treatment protocols. In this article, the pathophysiological mechanisms, molecular genetic aspects, and the dynamics of morphofunctional changes are represented in detail. Understanding the mechanisms of etiopathogenesis and the features of morphological changes observed in this cardiomyopathy and its more detailed study is fundamental in developing modern treatment methods to improve patients' quality and life expectancy.

Urotensin-II As a Promising Key-Point of Cardiovascular Disturbances Sequel.

Arterial hypertension is a highly urgent problem of modern medicine since the crisis of blood pressure control remains open, due to the increasing number of uncontrolled arterial hypertension. Today, one of the most critical problems of cardiology is the study of the mechanisms of development and progression of arterial hypertension. Therefore, our international and multidisciplinary working group presents a vision of a new therapeutic target - urotensin II in the pathogenesis of arterial hypertension. Thus, this article reflects the concept of the Armenian, Georgian and Iranian medical schools.

AC-Mode of Chemotherapy as a Trigger of Cardiac Syndrome X: A Case Study.

In the period of dynamic development of pharmacological possibilities in the modern oncology, unfortunately, the issue of cardiotoxicity of chemotherapy did not lost its urgent value. Cardiotoxicity implies structural and functional myocardial alteration, together with an increase in the concentration of highly sensitive markers of myocardial necrosis, in particular T and I troponins, and N-terminal pro-BNP, as well as with a subclinical or clinical decrease in the LVEF. It is noteworthy that cardiotoxicity is manifested not only by the development of anthracycline cardiomyopathy with a high risk of convention into heart failure. It also can cause various cardiovascular pathologies, in particular cardiac syndrome X. This study described chemotherapy-induced microvascular angina in 23-year-old otherwise heathy woman. The diagnosis is challenging for doctors, since microvascular flow may be only detected by using functional test.

Anthracycline Associated Disturbances of Cardiovascular Homeostasis.

Despite the dynamic progress of modern medicine, oncological and cardiovascular diseases (CVD) remain a severe economic burden worldwide. Therefore, the study of chemotherapeutic cardiotoxicity appears to be comprehensively demanded. Nowadays, pharmacological therapy in oncology has undoubtedly unprecedented development, but at the same time, the rates of cardiovascular complications of chemotherapy still remain unchanged. The well-established and highly effective, but at the same time, cardiotoxic anthracyclines have not lost their relevance. Furthermore, they remain indispensable components of an immense amount of chemotherapy regimens, such as AC, FAC, etc. Moreover, the anthracycline-containing chemotherapy regimens have become a standard of care in several cancer types. In the context of the above mentioned, the study of the pathophysiological mechanisms, biochemical aspects, and dynamics of the morphological remodeling of doxorubicin-induced cardiovascular homeostasis disturbances will enable finding new targets of pharmacological therapy, which either in the short or long perspectives, will have a beneficial effect, improving both the quality of life and prognosis of oncological patients. This article covers a versatile overview of the molecular mechanisms of doxorubicin-induced cardiotoxicity. The pathogenesis of cardiotoxicity assessment could help to explore specific molecular mechanisms that initiate cardiovascular alteration that may favorably affect the future development of targeted drugs that could prevent cardiovascular events in cancer patients.

Diabefit as a Modifier of Fructose-induced Impairment of Cardio-vascular System.

Today, cardiovascular diseases, due to their widespread prevalence, are among the most relevant biomedical problems in the modern world. The development of cardiovascular comorbidity among patients with diabetes mellitus is of high clinical urgency. Therefore, the study of cardiovascular risk modification among patients with diabetes mellitus is of paramount importance. In the context of the above, the data on the cardiotoxicity of fructose look very alarming since these patients usually use fructose as an affordable alternative to glucose. At the same time, it is an independent inducer of destabilization of cardiovascular homeostasis. Sixty rats were used in the experiment to study this problem. Modeling of fructose-induced overload was performed using a diabetic fructose supplement in an aqueous solution. The collection of herbs "Diabefit" was used as an infusion in addition to feeding highly enriched with fructose. The used markers which reflect the state of the heart and the blood vessels were: MDA, SOD, NO, and ET-1. MDA, ET-1, and NO concentrations demonstrated a significant increase in the fructose overload group and a significant decrease in the Diabefit group. At the same time, changes in SOD level as an indicator of the antioxidant reserve, on the contrary, implied a decrease in the group with a high fructose content and increased in the Diabefit group. All detected changes were associated with fructose-induced inhibition of SOD activity and its restoration using the Diabefit phyto-collection.

Hyperhomocysteinemia as a Link of Chemotherapy-Related Endothelium Impairment.

Atherosclerosis is a well-known risk factor of cardiovascular disease development. This research presents the AC mode of chemotherapy-related homocysteine level changes, with the simultaneous trimetazidine administration as a possible therapeutic inhibitor of chemotherapy-associated disturbances of morphofunctional homeostasis, for assessing the possible normalization effects. In order to the implementation of this experimental research, 80 Wistar rats were used. The chemotherapy was administered in AC mode. Trimetazidine was used as a stabilizer of homocysteine concentration. Analysis of homocysteine concentration was carried out by quantitative enzyme immunoassay. Given results state that AC-mode of chemotherapy modulates homocysteine production, a known risk factor for endothelial dysfunction development. At the same time, trimetazidine showed an unexpected limitation of homocysteine concentration. The obtained data indicate that hyperhomocysteinemia also plays a particular role in implementing the chemotherapy-induced cardiovascular disturbances continuum. While homocysteine's stabilizing properties of trimetazidine appear to be quite promising, withal further research is needed.