The role of dietary fatty acids in predicting myocardial structure in fat-fed rats

<p>Abstract</p> <p><it>Background</it></p> <p>Obesity increases the risk for development of cardiomyopathy in the absence of hypertension, diabetes or myocardial ischemia. Not all obese individuals, however, progress to heart failure. Indeed, obesity may provide protection from cardiovascular mortality in some populations. The fatty acid milieu, modulated by diet, may modify obesity-induced myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy in obese individuals.</p> <p><it>Methods</it></p> <p>Adult male Sprague-Dawley rats were fed 1 of the following 4 diets for 32 weeks: control (CON); 50% saturated fat (SAT); 40% saturated fat + 10% linoleic acid (SAT+LA); 40% saturated fat + 10% α-linolenic acid (SAT+ALA). Serum leptin, insulin, glucose, free fatty acids and triglycerides were quantitated. <it>In vivo </it>cardiovascular outcomes included blood pressure, heart rate and echocardiographic measurements of structure and function. The rats were sacrificed and myocardium was processed for fatty acid analysis (TLC-GC), and evaluation of potential modifiers of myocardial structure including collagen (Masson's trichrome, hydroxyproline quantitation), lipid (Oil Red O, triglyceride quantitation) and myocyte cross sectional area.</p> <p><it>Results</it></p> <p>Rats fed SAT+LA and SAT+ALA diets had greater cranial LV wall thickness compared to rats fed CON and SAT diets, in the absence of hypertension or apparent insulin resistance. Treatment was not associated with changes in myocardial function. Myocardial collagen and triglycerides were similar among treatment groups; however, rats fed the high-fat diets, regardless of composition, demonstrated increased myocyte cross sectional area.</p> <p><it>Conclusions</it></p> <p>Under conditions of high-fat feeding, replacement of 10% saturated fat with either LA or ALA is associated with thickening of the cranial LV wall, but without concomitant functional changes. Increased myocyte size appears to be a more likely contributor to early LV thickening in response to high-fat feeding. These findings suggest that myocyte hypertrophy may be an early change leading to gross LV hypertrophy in the hearts of "healthy" obese rats, in the absence of hypertension, diabetes and myocardial ischemia.</p

How vanadium and manganese compounds impact cardiac mitochondrial function

IntroductionVanadium and manganese are two biologically relevant redox-active first row transition metals. Both metals have been associated with protective and deleterious effects in the cardiovascular system depending on the biological context, chemical species and metal oxidation state investigated. Many studies have indicated that these metals elicit their effects in part by influencing mitochondrial function, with potential variations due to their redox properties and complexation.MethodsTo better understand these relationships, we investigated the effects of vanadium and manganese salts (VIVOSO4, NaVVO3, MnIICl2) and acetoacetate (Hacac) complexes (VIVO(acac)2 and MnII(acac)2) on murine cardiac mitochondrial function. Metal speciation calculations were performed to predict the chemical species present under biological assay conditions.Results and DiscussionBoth vanadium and manganese salts decreased rates of mitochondrial respiration in a concentration dependent manner, which was attenuated when the metals were complexed to an organic ligand. In contrast, only VIVOSO4 and VIVO(acac)2 induced significant mitochondrial swelling, with greater sensitivity over NaVVO3, MnIICl2, MnII(acac)2 and free Hacac ligand. Swelling induced by both vanadium(IV) species was fully abolished by inhibition of the mitochondrial calcium uniporter and was partially dependent upon the voltage-dependent anion channel. In addition to the simple monomeric form (VIVO(H2O)52+), a second active vanadium species is the dimer (VIVO)2(OH)5−, while for manganese the main active species is Mn2+. In summary, these studies demonstrate distinct effects of vanadium and manganese on cardiac mitochondrial function that vary in part with the chemical speciation and metal oxidation state

Alterations of biaxial viscoelastic properties of the right ventricle in pulmonary hypertension development in rest and acute stress conditions

Introduction: The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates.Methods: PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively.Results and Discussion: We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups—the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Abstract 297: Effects of p53 Stabilization During Heart Failure Progression on Telomere Repeat Binding Factor 2 and Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α in the SHHF Rat

The tumor suppressor protein p53 is a cellular stress sensor and transcription factor classically accepted to target the transcription of genes that induce senescence and apoptosis. Diverse stressors including genomic or telomeric DNA damage, telomere uncapping, hypoxia, oxidative stress, and mechanical stress increase stable cellular p53. In models of heart failure and in human failing hearts, p53 is increased. High p53 has also been suggested to be necessary for the transition from hypertrophy to heart failure. In recent years it has become clear that senescence and apoptosis may not be the only significant deleterious effects of increased cellular p53. It has been suggested that p53 can decrease mitobiogenesis and cellular ATP production by direct repression of PGC1-a expression. Additionally, P53 has been shown to stimulate the expression of Siah1, an E3 ubiquitin ligase that mediates degradation of the telomere binding protein TRF2. TRF2 loss is a form of telomere uncapping that, in cell culture models, causes a subsequent DNA damage response including further p53 stabilization. The relative importance of these p53 linked pathways has yet to be explored in the progression of hypertensive heart failure. Spontaneously Hypertensive Heart Failure rats (SHHF) rats were sacked at four stages during heart failure progression and LV removed for western blot analysis. Compared to young (2-4 month) rats, 14-15 month rats showed significantly increased p53 levels (2.3 fold), normal TRF2 levels, and slightly decreased PGC1-a (.98 fold). Old SHHFs (20-22mo) had p53, TRF2, and PGC1-a levels similar to 14-15 month rats (2.1, 1.09, and.83 fold, respectively). Rats with end stage heart failure showed a significant 4.5 fold increase in p53 expression, with a corresponding decrease in TRF2 (.74 fold, p=.087), and increase in PGC1-a (1.3 fold, nonsignificant). These data are in agreement with previous suggestions that increased p53 is most important during the transition from hypertrophy to heart failure, and suggest that levels of p53 encountered in the SHHF model have little effect on PGC1-a and mitobiogenesis, but may mediate an increase in telomere uncapping during heart failure.</jats:p