Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodeling

The renin angiotensin system (RAS) is integral to cardiovascular physiology, however, dysregulation of this system largely contributes to the pathophysiology of cardiovascular disease (CVD). It is well established that angiotensin II (Ang II), the main effector of the RAS, engages the angiotensin type 1 receptor and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodeling of the heart and vasculature, ultimately leading to the development and progression of various CVDs including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centered on the actions of angiotensin converting enzyme 2 (ACE2) and the resultant production of angiotensin-(1-7) (Ang-(1-7) from Ang II, antagonizes the actions of Ang II via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9), has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. This review will discuss the role of the counter-regulatory RAS peptides, Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodeling of the heart and vasculature

Construction of Cardiac Tissue Rings Using a Magnetic Tissue Fabrication Technique

Here we applied a magnetic force-based tissue engineering technique to cardiac tissue fabrication. A mixture of extracellular matrix precursor and cardiomyocytes labeled with magnetic nanoparticles was added into a well containing a central polycarbonate cylinder. With the use of a magnet, the cells were attracted to the bottom of the well and allowed to form a cell layer. During cultivation, the cell layer shrank towards the cylinder, leading to the formation of a ring-shaped tissue that possessed a multilayered cell structure and contractile properties. These results indicate that magnetic tissue fabrication is a promising approach for cardiac tissue engineering

Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life

Evolution of Scar Mechanical Properties During Myocardial Infarct Healing in Rat

The mechanics of healing myocardial infarcts are an important determinant of post-infarction left ventricular (LV) function and remodeling. Large animal infarct models are well studied; healing infarct scars have been shown to be mechanically and structurally anisotropic [1], and this anisotropy may help preserve LV function during some stages of healing [2]. At the same time, it has been suggested that the rat model of myocardial infarction is more similar to humans in the range of infarct sizes and observed LV dysfunction [3]. However, in the rat model, infarct mechanics and their effect on the overall LV function have not been described so far.</jats:p

Collagen Fiber Structure Correlates With Mechanical Environment in Healing Myocardial Infarcts

Mechanics of healing myocardial infarcts are an important determinant of ventricular function. Large collagen fibers are the major contributors to the mechanical properties of healing scar. It has been suggested that an anisotropic structure, as observed in healing pig scars, may help preserve ventricular function, and that the alignment of collagen fibers could be guided by the regional mechanical environment in the infarct — in pig scars the alignment of collagen fibers was in the direction of greatest stretch [1]. By contrast, in the standard rat model of infarction we found that scars are structurally and mechanically isotropic at all time points in healing [2].</jats:p

Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat

The mechanical properties of the healing scar are an important determinant of heart function following myocardial infarction. Yet the relationship between scar structure, scar mechanics, and ventricular function remains poorly understood, in part because no published study has tracked all of these factors simultaneously in any animal model. We therefore studied the temporal evolution of scar structure, scar mechanics, and left ventricular (LV) function in large anterior myocardial infarcts in rats. At 1, 2, 3, and 6 wk after left anterior descending coronary ligation, we examined LV function using sonomicrometry, infarct mechanical properties using biaxial mechanical testing, infarct structure using polarized light microscopy, and scar collagen content and cross-linking using biochemical assays. Healing infarcts in the rat were structurally and mechanically isotropic at all time points. Collagen content increased with time and was the primary determinant of scar mechanical properties. The presence of healing infarcts influenced systolic LV function through a rightward shift of the end-systolic pressure-volume relationship (ESPVR) that depended on infarct size, infarct collagen content, and LV dilation. We conclude that in sharp contrast to previous reports in large animal models, healing infarcts are structurally and mechanically isotropic in the standard rat model of myocardial infarction. On the basis of the regional strain patterns we observed in healing rat infarcts in this study and in healing pig infarcts in previous studies, we hypothesize that the local pattern of stretching determines collagen alignment in healing myocardial infarct scars

Розробка тестових операцій різною тривалості у часі для підвищення якості верифікації формули ефективності

Selection of an indicator for assessment of effectiveness of operations is a very essential step, because this choice predetermines the mode of operation for all functional systems at an enterprise.An axiom is the thesis that all technological processes without exception must be optimized using a coordinated optimization criterion. This is possible only in case if the effectiveness formula is used as a unified criterion. Only in this case, maximizing of financial capabilities of an enterprise is provided.In order to identify the original effectiveness formula among a set of estimation indicators, which cannot be distinguished based on formal features, it is necessary to use a scientifically substantiated verification method.A limited class of models of operations with distributed parameters of different duration is determined. Creation of such a class is the most difficult problem, since comparison of operations of different duration requires taking into account the time factor, and the distributed nature of resource consumption and resource transfer in time significantly complicates the problem.To solve this problem, at the first stage, the rules of composition of an operation with distributed parameters using simple global models of operations with different duration were determined. At the second stage, for each simple model of an operation, there was formed a correspondent simple model of an operation with a longer duration, effectiveness of which was higher than that of the original operation by definition.At the final stage, we formed a limited class of global models of operations with distributed parameters of different duration with the use of the original and formed simple models of operations.Development of verification method by determining the class of operations with distributed parameters of different duration significantly enhances reliability and validity of results of verification of the estimation indicator, which is supposed to be used as an effectiveness indicator and an optimization criterion.Работа относится к области верификации кибернетических оценочных показателей, в частности, к решению задачи определения ограниченного класса операций с распределенными параметрами, объекты которого имеют предопределенную рейтинговую эффективность. В рамках исследования определяются правила формирования операционных объектов, которые могут использоваться для тестирования оценочных показателей на предмет возможности их использования в качестве формулы эффективностиРобота відноситься до області верифікації кібернетичних оціночних показників, зокрема, до вирішення завдання визначення обмеженого класу операцій з розподіленими параметрами, об'єкти якого мають наперед визначену рейтингову ефективність. В рамках дослідження визначаються правила формування операційних об'єктів, які можуть використовуватися для тестування оціночних показників на предмет можливості їх використання в якості формули ефективност

Fiber-Based Constitutive Model of Myocardial Scar Tissue

It has largely been accepted that collagen fibers play an important role in the mechanics of myocardial scar tissue; however, few studies have performed both mechanical and structural analysis on the same samples to confirm this. Therefore, the goal of this study was to combine both types of analysis with a structure-based constitutive model, which incorporates measured collagen fiber orientations, to gain a better understanding of the structural basis for the mechanics of two-week-old scar tissue.</jats:p

Розробка тестових операцій різною тривалості у часі для підвищення якості верифікації формули ефективності

Selection of an indicator for assessment of effectiveness of operations is a very essential step, because this choice predetermines the mode of operation for all functional systems at an enterprise.An axiom is the thesis that all technological processes without exception must be optimized using a coordinated optimization criterion. This is possible only in case if the effectiveness formula is used as a unified criterion. Only in this case, maximizing of financial capabilities of an enterprise is provided.In order to identify the original effectiveness formula among a set of estimation indicators, which cannot be distinguished based on formal features, it is necessary to use a scientifically substantiated verification method.A limited class of models of operations with distributed parameters of different duration is determined. Creation of such a class is the most difficult problem, since comparison of operations of different duration requires taking into account the time factor, and the distributed nature of resource consumption and resource transfer in time significantly complicates the problem.To solve this problem, at the first stage, the rules of composition of an operation with distributed parameters using simple global models of operations with different duration were determined. At the second stage, for each simple model of an operation, there was formed a correspondent simple model of an operation with a longer duration, effectiveness of which was higher than that of the original operation by definition.At the final stage, we formed a limited class of global models of operations with distributed parameters of different duration with the use of the original and formed simple models of operations.Development of verification method by determining the class of operations with distributed parameters of different duration significantly enhances reliability and validity of results of verification of the estimation indicator, which is supposed to be used as an effectiveness indicator and an optimization criterion.Работа относится к области верификации кибернетических оценочных показателей, в частности, к решению задачи определения ограниченного класса операций с распределенными параметрами, объекты которого имеют предопределенную рейтинговую эффективность. В рамках исследования определяются правила формирования операционных объектов, которые могут использоваться для тестирования оценочных показателей на предмет возможности их использования в качестве формулы эффективностиРобота відноситься до області верифікації кібернетичних оціночних показників, зокрема, до вирішення завдання визначення обмеженого класу операцій з розподіленими параметрами, об'єкти якого мають наперед визначену рейтингову ефективність. В рамках дослідження визначаються правила формування операційних об'єктів, які можуть використовуватися для тестування оціночних показників на предмет можливості їх використання в якості формули ефективност