The Markers of Endothelial Activation

Biomarkers are biological indicators of processes that are part of ethiopathogenesis of the diseases, and can, but do not have to be causal to diseases. One very important question is how specific and sensitive the marker is, since one molecule can appear in many conditions. Biomarkers of endothelial cell activation can be very diverse, from biochemical/metabolic to functional biomarkers. Activation of endothelial cells is part of physiological as well as pathophysiological response of cardiovascular system in conditions as physical activity, growth, pregnancy and in all cardiometabolic diseases (e.g., hypertension, diabetes mellitus, autoimmune inflammatory diseases, coronary artery disease, atherosclerosis, ischemia and reperfusion, etc.). During activation, there is a change in endothelial cell morphology and function, which could be a defensive response of endothelium to provoking factor or could lead to increased risk for the injury and end organ damage. This chapter aims to overview current knowledge on established biomarkers of normal and disease-related endothelial activation and to provide information on novel, potential biomarkers in common cardiometabolic diseases

Time of Anderson-Fabry Disease Detection and Cardiovascular Presentation

BACKGROUND: Anderson-Fabry disease is an X-linked inherited disease, which manifests in a different manner depending on gender and genotype. Making a working diagnosis of Anderson-Fabry disease is difficult because of several reasons: (a) that it is a multiorgan disease with wide variety of phenotypes, (b) different timelines of presentation, (c) gender differences, and (d) possible coexistence with other comorbidities. Late-onset/cardiac type of presentation with minimal involvement of other organs can additionally make diagnosis difficult. AIM: To describe different cardiac manifestations at different time points in the course of the disease: (1) 72-year-old female (echocardiography detection), heterozygote, significant left and mild right ventricular hypertrophy; (2) 62-year-old male (echocardiography detection), hemizygote, left ventricular hypertrophy, implanted cardiac pacemaker, a performed percutaneous coronary intervention after myocardial infarction, degenerative medium degree aortic valve stenosis; (3) 45-year-old female (asymptomatic/family screening), heterozygote, thickened mitral papillary muscle, mild left ventricular hypertrophy, first degree diastolic dysfunction; and (4) 75-year-old female (symptomatic/family screening), heterozygote, cardiomyopathy with reduced left ventricular ejection fraction after heart surgery (mitral valve annuloplasty and plastic repair of the tricuspid valve). CONCLUSION: All patients have Anderson-Fabry disease but with different clinical presentations depending on the gender, the type of mutation, and the time of detection. All these features can make the patients' profiles unique and delay the time of detection

Oxidative Stress in Ischemic Heart Disease

One of the novel interesting topics in the study of cardiovascular disease is the role of the oxidation system, since inflammation and oxidative stress are known to lead to cardiovascular diseases, their progression and complications. During decades of research, many complex interactions between agents of oxidative stress, oxidation, and antioxidant systems have been elucidated, and numerous important pathophysiological links to na number of disorders and diseases have been established. This review article will present the most relevant knowledge linking oxidative stress to vascular dysfunction and disease. The review will focus on the role of oxidative stress in endotheleial dysfunction, atherosclerosis, and other pathogenetic processes and mechanisms that contribute to the development of ischemic heart disease

Angiotensin II Type 1 Receptor is Involved in Flow-Induced Vasomotor Responses of Isolated Middle Cerebral Arteries: Role of Oxidative Stress

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-week old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilation was compared with control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and cyclooxygenase inhibitor indomethacin (Indo) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by Indo only at Δ100 mmHg, whereas l-NAME had no effect. In losartan group, Tempol (a superoxide scavenger) restored dilatation, whereas Tempol + l-NAME together significantly reduced FID compared with restored dilatation with Tempol alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared with control group, whereas in flow condition increased the NO and ROS production in losartan group and had no effect in the control group. In losartan group, Tempol decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of ANG II, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.NEW & NOTEWORTHY The AT1R blockade impaired the endothelium-dependent, both flow- and acetylcholine-induced dilations of MCA by decreasing vascular NO production and increasing the level of vascular and systemic oxidative stress, whereas it mildly influenced the vascular wall inflammatory phenotype, but had no effect on the systemic inflammatory response. Our data provide functional and molecular evidence for an important role of AT1 receptor activation in physiological conditions, suggesting that AT1 receptors have multiple biological functions