Fibrosis in hypertensive heart disease: role of the renin-angiotensin-aldosterone system

Structural homogeneity of cardiac tissue is governed by mechanical and humoral factors that regulate cell growth, apoptosis, phenotype, and extracellular matrix turnover. ANGII has endocrine, autocrine, and paracrine properties that influence the behavior of cardiac cells and matrix by AT1 receptor binding. Various paradigms have been suggested, including ANGII-mediated up-regulation of collagen types I and III formation and deposition in cardiac conditions, such as HHD. A growing body of evidence, however, deals with the potential role of aldosterone, either local or systemic, in inducing cardiac fibrosis. Aldosterone might also mediate the profibrotic actions of ANGII. To reduce the risk of heart failure that accompanies HHD, its adverse structural remodeling (eg, myocardial hypertrophy and fibrosis) must be targeted for pharmacologic intervention. Cardioprotective agents must reverse not only the exaggerated growth of cardiac cells, but also regress existing abnormalities in fibrillar collagen. Available experimental and clinical data suggest that agents interfering with ACE, the AT1 receptor, or the mineralocorticoid receptor may provide such a cardioprotective effect

Myocardial fibrosis in arterial hypertension

It is now accepted that, in addition to left ventricular hypertrophy, hypertensive heart disease is characterized by alterations in myocardial structure, leading to loss of tissue homogeneity and pathological remodelling. It is time to recognize that, in hypertensive heart disease, it is not only the quantity but also the quality of the myocardium that is responsible for adverse cardiovascular events. The data reviewed here indicate that, in patients with hypertensive heart disease, myocardial fibrosis predisposes to an enhanced risk for diastolic and/or systolic ventricular dysfunction, symptomatic heart failure, ischaemic heart disease and arrhythmias

QUANTIZATION FOR A SET OF DISCRETE DISTRIBUTIONS ON THE SET OF NATURAL NUMBERS

The quantization scheme in probability theory deals with finding a best approximation of a given probability distribution by a probability distribution that is supported on finitely many points. In this paper, first we state and prove a theorem, and then give a conjecture. We verify the conjecture by a few examples. Assuming that the conjecture is true, for a set of discrete distributions on the set of natural numbers we have calculated the optimal sets of n-means and the nth quantization errors for all positive integers n. In addition, the quantization dimension is also calculated

Exploiting the Passive Dynamics of a Compliant Leg to Develop Gait Transitions

In the area of bipedal locomotion, the spring loaded inverted pendulum (SLIP) model has been proposed as a unified framework to explain the dynamics of a wide variety of gaits. In this paper, we present a novel analysis of the mathematical model and its dynamical properties. We use the perspective of hybrid dynamical systems to study the dynamics and define concepts such as partial stability and viability. With this approach, on the one hand, we identified stable and unstable regions of locomotion. On the other hand, we found ways to exploit the unstable regions of locomotion to induce gait transitions at a constant energy regime. Additionally, we show that simple non-constant angle of attack control policies can render the system almost always stable

Association of increased plasma cardiotrophin-1 with inappropriate left ventricular mass in essential hypertension

Inappropriate left ventricular mass is present when the value of left ventricular mass exceeds individual needs to compensate hemodynamic load imposed by increased blood pressure. The goal of this study was to investigate whether plasma concentration of cardiotrophin-1, a cytokine that induces exaggerated hypertrophy in cardiomyocytes with hypertensive phenotype, is related to inappropriate left ventricular mass in patients with essential hypertension. The study was performed in 118 patients with never-treated hypertension and without prevalent cardiac disease. The left ventricular mass prediction from stroke work (systolic blood pressurexDoppler stroke volume), sex, and height (in meters(2.7)) was derived. An observed left ventricular mass/predicted left ventricular mass value >128% defined inappropriate left ventricular mass. Plasma cardiotrophin-1 was measured by an enzyme-linked immunosorbent assay. The studies were repeated in a group of 45 patients after 1 year of antihypertensive treatment. At baseline 67 and 51 patients presented with appropriate and inappropriate left ventricular mass, respectively. Plasma cardiotrophin-1 was higher (P<0.001) in patients with inappropriate mass than in patients with appropriate mass and normotensive controls. A direct correlation was found between cardiotrophin-1 and observed left ventricular mass/predicted left ventricular mass ratio (r=0.330, P<0.001) in all hypertensive patients. After treatment, plasma cardiotrophin-1 decreased and increased in patients in which inappropriate left ventricular mass regressed and persisted, respectively, despite a similar reduction of blood pressure in the 2 subgroups of patients. Albeit descriptive in nature, these results suggest the hypothesis that an excess of cardiotrophin-1 may contribute to inappropriate left ventricular growth in hypertensive patients

Impact of treatment on myocardial lysyl oxidase expression and collagen cross-linking in patients with heart failure

The aim of this study was to investigate whether torasemide modifies collagen cross-linking in the failing human heart. We analyzed the degree of cross-linking and the expression of the enzyme lysyl oxidase, which regulates cross-linking, in the myocardium of patients with chronic heart failure at baseline and after 8 months of treatment with either torasemide or furosemide in addition to their standard heart failure therapy. Whereas lysyl oxidase protein expression was very scarce in normal hearts, it was highly expressed in failing hearts. Cross-linking was increased (P<0.001) in heart failure patients compared with normal hearts. These 2 parameters decreased (P=0.021 and P=0.034) in torasemide-treated patients and remained unchanged in furosemide-treated patients. In addition, more (P=0.009) patients showed normalization of left ventricular chamber stiffness in the torasemide subgroup than in the furosemide subgroup after treatment. Lysyl oxidase expression correlated with cross-linking (r=0.661; P<0.001), and cross-linking correlated with left ventricular chamber stiffness (r=0.452; P=0.002) in all patients. These findings show for the first time that lysyl oxidase overexpression is associated with enhanced collagen cross-linking in the failing human heart. In addition, we report that the ability of torasemide to correct both lysyl oxidase overexpression and enhanced collagen cross-linking results in normalization of left ventricular chamber stiffness in patients with heart failure. Lysyl oxidase may thus represent a target for reduction of stiff collagen and improvement of left ventricular mechanical properties in heart failure patients

Myocardial Response to Biomechanical Stress

Biomechanical stress of the myocardium is the situation resulting from hypoxia, hypertension, and other forms of myocardial injury, that invariably lead to increased demands for cardiac work and/or loss of functional myocardium. As a consequence of biomechanical stress a number of responses develop involving all the myocardial cells, namely cardiomyocytes. As a result some myocardial phenotypic changes develop that are initially compensatory (i.e., hypertrophy) but which may mediate the eventual decline in myocardial function that occurs with the transition from hypertrophy to failure in conditions of persistent stress (i.e., apoptosis and fibrosis). This review focuses on the steps involved in the response of the myocardium to biomechanical stress and highlights the most recent developments in the molecular mechanisms involved in the development of heart failure

Respuestas del miocardio al estrés biomecánico

El estrés biomecánico del miocardio hace referencia a la situación que se genera cuando, debido a la hipertensión, la hipoxia u otras formas de daño miocárdico, están aumentadas las demandas de trabajo cardíaco y/o se ha perdido miocardio funcionante. Como consecuencia del estrés biomecánico se producen diversas respuestas que afectan a todas las células miocárdicas, en particular a los cardiomiocitos. El resultado final de las mismas son distintas modificaciones fenotípicas que inicialmente son compensadoras (p. ej., hipertrofia), pero que si persiste el estrés pueden mediar la transición de la hipertrofia a la insuficiencia cardíaca (p. ej., apoptosis y fibrosis). Esta revisión se centra en la descripción de las distintas fases de las respuestas miocárdicas al estrés, así como en la consideración de los hallazgos más recientes sobre los mecanismos moleculares implicados en el desarrollo de insuficiencia cardíaca

Retinal blood vessels extraction using probabilistic modelling

© 2014 Kaba et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.The Department of Information Systems, Computing and Mathematics, Brunel University