Abstract
The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls.
Highlights
Cardiovascular diseases remain the major cause of morbidity and mortality in industrialized Western nations
Serum cholesterol levels in animals administered feed supplemented with 2% cholesterol and rabbits receiving normal feed were evaluated during the study period
One example of the interaction between these two organ systems, which may emerge as an area for development of novel therapies, is that the disruption of normal regulation by the liver of platelet-activating factor acetyl-hydrolase may strongly contribute to atherosclerosis, since this enzyme is low density lipoprotein (LDL)-associated [21]
Summary
Cardiovascular diseases remain the major cause of morbidity and mortality in industrialized Western nations In these disorders, death most often occurs as a consequence of atherosclerosis, leading to stroke, ischemia, myocardial infarction, heart failure and other syndromes characterized by severely dysregulated inflammatory processes and their resulting degradation of tissue function [1,2]. Mitochondrial electron-transfer complexes are major sources of ROS, and oxidative damage to the electron transport complexes that are in close proximity to these ROS sources, e.g., cytochrome c oxidase, are expected to inhibit electron transport Such inhibition increases electron leakage, leading to further ROS production [9]. The core hypothesis of the present investigation is that oxidative stress induced in a hypercholesterolemic rabbit model by sustained cholesterol diets promotes pathological changes in ways that may be revealed by changes on the molecular level. Corollary studies included assessment of the role of cytochrome c oxidase (COX) enzymes in regulating ATP metabolism and hosting adaptive, anti-inflammatory processes, including ROS scavenging
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
