cardiovascular-agents and Metabolic-Diseases

Topics: Animals; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Drug Development; Drug Discovery; Gastrointestinal Microbiome; Humans; Metabolic Diseases

Currently, the percentage of non-specific myocardial lesions of non-inflammatory genesis has significantly increased in the structure of cardiovascular diseases in children and adolescents. Cardiomyopathies are a cluster of myocardial diseases that have become more of interest by cardiologists, morphologists, geneticists, and cardiac surgeons. Cardiomyopathies in children are regarded as a severe pathology characterized by a progressive course, resistance to therapy, and result in an unfavourable prognosis. The current article presents data from international publications dedicated to cardiomyopathy diagnostics in children. This article deals with terminology issues in compliance with international disease classification, primary diagnostic criteria of non-coronary myocardium pathology, and modern methods of diagnostics and pharmacotherapy.

Topics: Age of Onset; Animals; Cardiology; Cardiomyopathies; Cardiovascular Agents; Energy Metabolism; Humans; Metabolic Diseases; Myocardium; Pediatrics; Predictive Value of Tests; Risk Factors; Terminology as Topic; Treatment Outcome

The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported.. This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research.. Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017.. EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated haemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant).. EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.

Topics: Animals; Anti-Inflammatory Agents; Camellia sinensis; Cardiovascular Agents; Cardiovascular Diseases; Catechin; Humans; Metabolic Diseases; Tea

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date.

Topics: Animals; Animals, Genetically Modified; Cardiovascular Agents; Cardiovascular Diseases; Disease Models, Animal; Drug Discovery; Genetic Predisposition to Disease; Humans; Metabolic Diseases; Phenotype; Species Specificity; Zebrafish

Bile acids (BA), for decades considered only to have fat-emulsifying functions in the gut lumen, have recently emerged as novel cardio-metabolic modulators. They have real endocrine effects, acting via multiple intracellular receptors in various organs and tissues. BA affect energy homeostasis through the modulation of glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor (FXR), as well as the cytoplasmic membrane G protein-coupled BA receptor TGR5 in a variety of tissues; although numerous other intracellular targets of BA are also in play.The roles of BA in the pathogenesis of diabetes, obesity, metabolic syndrome, and cardiovascular diseases are seriously being considered, and BA and their derivatives seem to represent novel potential therapeutics to treat these diseases of civilization.

Topics: Animals; Anti-Obesity Agents; Bile Acids and Salts; Cardiovascular Agents; Cardiovascular Diseases; Drug Discovery; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Intestinal Mucosa; Intestines; Lipid Metabolism; Metabolic Diseases; Probiotics; Signal Transduction

Despite being used for a long time as food and beverage by Brazilian people who live on the Amazon bay, only in the beginning of this century, açaí berries have been the object of scientific research. Açaí berries are rich in polyphenols that probably explains its versatile pharmacological actions and huge consumption, not only in Brazil but also in Europe and United States. In this review, not all but some pharmacological aspects of açaí berries are analyzed. Chemical and pharmacological differences between extracts obtained from the skin and seed of açaí are considered. Polyphenols from the seed of açaí increase endothelial nitric oxide production leading to endothelium-dependent relaxation, reduce reactive oxygen species and regulate key targets associated with lipid metabolism in different conditions such as hypertension, renal failure, and metabolic syndrome. We review the novel mechanisms of actions of açaí on different targets which could trigger the health benefits of açaí such as antioxidant, vasodilator, antihypertensive, cardioprotector, renal protector, antidyslipidemic, antiobesity, and antidiabetic effects in cardiovascular and metabolic disturbances.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Euterpe; Fruit; Humans; Metabolic Diseases; Phytochemicals; Phytotherapy; Plant Extracts; Plants, Medicinal

Modulation of the low affinity adenosine receptor subtype, the A2b adenosine receptor (A2bAR), has gained interest as a therapeutic target in various pathologic areas associated with cardiovascular disease. The actions of the A2bAR are diverse and at times conflicting depending on cell and tissue type and the timing of activation or inhibition of the receptor. The A2bAR is a promising and exciting pharmacologic target, however, a thorough understanding of A2bAR action is necessary to reach the therapeutic potential of this receptor. This review will focus on the role of the A2bAR in various cardiovascular and metabolic pathologies in which the receptor is currently being studied. We will illustrate the complexities of A2bAR signaling and highlight areas of research with potential for therapeutic development.

Topics: Adenosine A2 Receptor Agonists; Adenosine A2 Receptor Antagonists; Animals; Cardiovascular Agents; Cardiovascular Diseases; Humans; Metabolic Diseases; Molecular Targeted Therapy; Receptor, Adenosine A2B; Signal Transduction

Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. Because conventional antiarrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD.

Topics: Arrhythmias, Cardiac; Calcium Signaling; Cardiovascular Agents; Death, Sudden, Cardiac; Gap Junctions; Heart Conduction System; Heart Diseases; Homeostasis; Humans; Ion Channel Gating; Ion Channels; Membrane Potentials; Metabolic Diseases; Mitochondria, Heart; Myocardium; Oxidation-Reduction; Oxidative Stress; Potassium; Reactive Oxygen Species; Sodium

Medicinal chemistry has been transformed by major technological and conceptual innovations over the last three decades: structural biology and bioinformatics, structure and property based molecular design, the concepts of multidimensional optimization (MDO), in silico and experimental high-throughput molecular property analysis. The novel technologies advanced gradually and in synergy with biology and Roche has been at the forefront. Applications in drug discovery programs towards new medicines in cardiovascular and metabolic diseases are highlighted to show impact and advancement: the early discovery of endothelin antagonists for endothelial dysfunction (Bosentan), 11-beta hydroxysteroid dehydrogenase (11β-HSD1) inhibitors for dysregulated cellular glucocorticoid tonus (type 2 diabetes and metabolic syndrome) and non-covalent hormone sensitive lipase (HSL) inhibitors to study the scope of direct inhibition of lipolysis in the conceptual frame of lipotoxicity and type 2 diabetes.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Design; Humans; Metabolic Diseases

The therapeutic areas of infectious diseases and oncology have benefited from abundant scaffold diversity in natural products, able to interact with many specific targets within the cell and indeed for many years have been source or inspiration for the majority of FDA approved drugs. The present review describes natural products (NPs), semi-synthetic NPs and NP-derived compounds that have undergone clinical evaluation or registration from 2005 to 2010 by disease area i.e. infectious (bacterial, fungal, parasitic and viral), immunological, cardiovascular, neurological, inflammatory and related diseases and oncology.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Biological Products; Cardiovascular Agents; Cardiovascular Diseases; Communicable Diseases; Drug Discovery; Humans; Inflammation; Metabolic Diseases; Neoplasms; Nervous System Diseases; Plant Extracts; Plants, Medicinal

TF (tissue factor) is the main trigger of the coagulation cascade; by binding Factor VIIa it activates Factor IX and Factor X, thereby resulting in fibrin formation. Various stimuli, such as cytokines, growth factors and biogenic amines, induce TF expression and activity in vascular cells. Downstream targets of these mediators include diverse signalling molecules such as MAPKs (mitogen-activated protein kinases), PI3K (phosphoinositide 3-kinase) and PKC (protein kinase C). In addition, TF can be detected in the bloodstream, known as circulating or blood-borne TF. Many cardiovascular risk factors, such as hypertension, diabetes, dyslipidaemia and smoking, are associated with increased expression of TF. Furthermore, in patients presenting with acute coronary syndromes, elevated levels of circulating TF are found. Apart from its role in thrombosis, TF has pro-atherogenic properties, as it is involved in neointima formation by inducing vascular smooth muscle cell migration. As inhibition of TF action appears to be an attractive target for the treatment of cardiovascular disease, therapeutic strategies are under investigation to specifically interfere with the action of TF or, alternatively, promote the effects of TFPI (TF pathway inhibitor).

Topics: Blood Coagulation; Cardiovascular Agents; Cardiovascular Diseases; Humans; Metabolic Diseases; Thromboplastin

Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) control the development and homeostasis of multiple tissue types in many organisms, from humans to invertebrates. These morphogens are expressed in a tissue-specific manner and they signal by binding to serine-threonine kinase receptors, resulting in coordinated changes in gene expression that regulate the differentiation and development of multiple tissue types. In addition, these proteins are regulated post-transcriptionally through binding to several soluble proteins. In this review we focus on a subset of BMPs and GDFs that have been implicated in the pathophysiology of type 2 diabetes and cardiovascular disease.

Topics: Animals; Atherosclerosis; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Growth Differentiation Factor 3; Humans; Hypertension, Pulmonary; Hypoglycemic Agents; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Metabolic Diseases; Signal Transduction; Transforming Growth Factor beta

Topics: C-Reactive Protein; Cardiovascular Agents; Cardiovascular Diseases; Humans; Incidence; Metabolic Diseases; Predictive Value of Tests; Risk

Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Hypolipidemic Agents; Lipid Metabolism; Metabolic Diseases; Obesity; Oxidative Stress; Renal Insufficiency; Risk Factors; Risk Reduction Behavior; Sex Factors; Troponin; Weight Loss

Coronary artery disease (CAD) is the leading cause of adult deaths in our country. In clinical practice, an adequate level of secondary prevention towards CAD primarily requires full recognition of the distribution of risk factors. The aim of our study was to determine the prevalence of coronary risk factors and the use of prophylactic drugs among patients who have an angiographically proven CAD in our centre, and to compare it with those of the EUROASPIRE I and II studies.. Cross-sectional, observational study.. Our patients comprise 617 subjects (516 male, mean age 57.2 +/- 10.8 years) who underwent an angiography between January 2000 and May 2000 for the first time and in whom significant coronary lesions were detected. Age, gender, family history of premature CAD (FH), diabetes mellitus (DM), hypertension (HT), lipid profile, smoking, body mass index, waist circumference, hip circumference and physical activity data were recorded prior to angiography. The medical treatments received by these cases at discharge from hospital were investigated. Data thus obtained were compared with the results of the EUROASPIRE I and II trials, which studied the frequency of existing risk factors and prophylactic drug use among CAD patients in European countries.. Hyperlipidaemia, FH, DM, HT, smoking, obesity, central obesity were found in 52, 26, 20, 41, 65, 18 and 29% of patients, respectively. The use of antiplatelets, beta-blockers, ACE inhibitors, statins and calcium antagonists were 99, 86, 40, 63 and 16%, respectively.. Upon comparison of the risk factors, prevalence of obesity and DM was found to be similar to the average of nine European countries among our subjects. Smoking was found to be considerably higher, whereas HT, hyperlipidaemia and family history of premature CAD were lower than the European average within our subjects. In our cases the frequency of prophylactic drug usage at discharge was higher than the European means.

Topics: Adult; Aged; Anticipation, Genetic; Cardiovascular Agents; Chemoprevention; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Epidemiologic Factors; Exercise; Female; Hematologic Agents; Humans; Hypertension; Male; Metabolic Diseases; Middle Aged; Obesity; Observation; Prevalence; Risk Factors; Smoking; Turkey

To examine discrepancies between co-morbidity of patients included in pre-marketing clinical trials of cardiovascular drugs and patients from daily practice, representing the actual users after marketing, and to investigate the availability of data regarding co-morbidity in registration files.. Data were collected from phase III trials of registration files of 16 drugs, registered in the Netherlands in the period 1985 through 1994 for the indications hypertension, angina pectoris or hypercholesterolemia, and from a general practitioners database. Patients were selected who used drugs from the same therapeutic classes for the same indication as the patients in the pre-marketing trials. Prevalences of concomitant cardiovascular, endocrine and metabolic diseases were compared between pre- and postmarketing populations. Discrepancies were defined as more than 10% difference in prevalences.. Data regarding co-morbidity were present in 13 out of 16 registration files and differed in format of reporting. For all indications, coexisting cardiovascular, endocrine and metabolic diseases were less prevalent in the pre-marketing populations, except ischemic heart disease, which was more prevalent coexisting with angina pectoris and hypercholesterolemia. Discrepancies were found for hypertensive disease, heart failure, diabetes mellitus and myocardial infarction.. Phase III trials testing cardiovascular drugs included patients with concomitant cardiovascular, endocrine and metabolic diseases, but discrepancies were present with patients in daily practice. Development of guidelines for uniform collection and reporting of co-morbidity data in pre-marketing trials is recommended, as well as further utilization of data.

Topics: Angina Pectoris; Cardiovascular Agents; Clinical Trials, Phase III as Topic; Comorbidity; Databases, Factual; Family Practice; Humans; Hypercholesterolemia; Hypertension; Metabolic Diseases; Netherlands; Patient Selection; Pharmacoepidemiology; Prevalence; Registries

The records of 268 patients were used to assess the effects of five disease/drug complexes on the number of postinsertion visits in complete denture wearers. The data were analyzed with SAS and BMDP computer packages. The results showed a statistically significant increase in the number of postinsertion visits in patients who had central nervous system or psychiatric disorders. Practitioners are alerted to consider the ergonomic implications at the outset of treatment.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Central Nervous System Diseases; Chi-Square Distribution; Dental Care for Aged; Dental Care for Chronically Ill; Denture Retention; Denture, Complete; Diabetes Complications; Diabetes Mellitus; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Masticatory Muscles; Mental Disorders; Metabolic Diseases; Middle Aged; Mouth Diseases; Movement; Office Visits; Pain; Prosthesis Fitting; Respiratory Tract Diseases; Retrospective Studies; Xerostomia