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

On the importance of nonlinear modeling in computer performance prediction

Computers are nonlinear dynamical systems that exhibit complex and sometimes even chaotic behavior. The models used in the computer systems community, however, are linear. This paper is an exploration of that disconnect: when linear models are adequate for predicting computer performance and when they are not. Specifically, we build linear and nonlinear models of the processor load of an Intel i7-based computer as it executes a range of different programs. We then use those models to predict the processor loads forward in time and compare those forecasts to the true continuations of the time seriesComment: Appeared in "Proceedings of the 12th International Symposium on Intelligent Data Analysis

Perceived Instability, Pain, and Psychological Factors Predict Function and Disability in Individuals with Chronic Ankle Instability

Context: Chronic ankle instability (CAI) is associated with residual instability, pain, decreased function, and increased disablement. Injury-related fear has been associated with CAI, although its relationship to other impairments is unclear. The Fear-Avoidance Model is a theoretical framework hypothesizing a relationship between injury-related fear, chronic pain, pain catastrophizing, and disability. It has been useful in understanding fear\u27s influence in other musculoskeletal conditions but has yet to be studied in those with CAI. Objective: To explore relationships between instability, pain catastrophizing, injury-related fear, pain, ankle function, and global disability in individuals with CAI. Design: Cross-Sectional Study Setting: Anonymous online survey Patients or Other Participants: A total of 259 people, recruited via e-mail and social media, with a history of ankle sprain completed the survey; of those, 126 participants (age=32.69±4.38, female=84.92%, highly active=73.81%) were identified to have CAI and were included in the analysis. Main Outcome Measure(s): Demographics included gender identity, age, and physical activity level. Assessments encompassed the Identification of Functional Ankle Instability (instability), the Pain Catastrophizing Scale (pain catastrophizing), the Tampa Scale of Kinesiophobia-11 (injury-related fear), a numeric pain rating scale and activity-based question (pain presence), the Quick-FAAM (ankle function), and the modified Disablement in the Physically Active Scale (disability). Relationships between variables were explored through correlation and regression analyses. Results: After controlling for instability and pain, pain catastrophizing and injury-related fear were significantly related to function and disability ratings in individuals with CAI. Together, the variables predicted 48.7% (P\u3c.001) variance in function and 44.2% (P\u3c.001) variance in disability. Conclusions: Greater instability, pain, greater pain catastrophizing, and greater injury-related fear were predictive of decreased function and greater disability in those with CAI. This is consistent with the hypothesized relationships in the Fear-Avoidance Model, although further investigation is needed to determine causality of these factors in the development of CAI

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

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

Biochemical Diagnosis of Hypertensive Myocardial Fibrosis

A substantial increase in fibrillar collagen has been observed in the left cardiac ventricle of animals and humans with arterial hypertension. Hypertensive myocardial fibrosis is the result of both increased collagen types I and III due to the fact that its synthesis by fibroblasts and myofibroblasts is stimulated and its extracellular collagen degradation unchanged or decreased extracellular collagen degradation. Hemodynamic and non-hemodynamic factors may be involved in the disequilibrium between collagen synthesis and degradation that occurs in hypertension. As shown experimentally and clinically, an exaggerated rise in fibrilar collagen content promotes abnormalities of cardiac function, contributes to the decrease in coronary reserve and facilitates alterations in the electrical activity of the left ventricle. Although microscopic examination of cardiac biopsies is the most reliable method for documenting and measuring myocardial fibrosis, the development of non-invasive methods to indicate the presence of myocardial fibrosis in hypertensive patients would be useful. We have therefore applied a biochemical method based on the measurement of serum peptides derived from the tissue formation when synthesized and degradation of fibrillar collagens to monitor the turnover of these molecules in rats with spontaneous hypertension and patients with essential hypertension

Very Low Temperature Tunnelling Spectroscopy in the heavy fermion superconductor PrOs4_4Sb12_{12}

We present scanning tunnelling spectroscopy measurements on the heavy fermion superconductor PrOs$_4$Sb$_{12}$. Our results show that the superconducting gap opens over a large part of the Fermi surface. The deviations from isotropic BCS s-wave behavior are discussed in terms of a finite distribution of values of the superconducting gap.Comment: 4 pages, 4 figure