Search

· Cholesterol-lowering nutraceuticals and functional foods play an important role in reducing the risk of coronary heart disease by improving the plasma lipoprotein profile. · Hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol levels, a preponderance of small, dense LDL particles, and an accumulation of cholesterol-rich remnant particles–emerged as the greatest ˵competitor″ of LDL cholesterol among lipid risk factors for cardiovascular disease. · Plant-derived nutraceuticals exhibit varied lipid-lowering effects due to the presence of a number of bioactive compounds which vary with individual nutraceuticals and functional foods. · Future studies could profitably focus on the interaction of the active ingredients with the expression of the genes involved in cholesterol metabolism and the synergistic effects of nutraceuticals on the regulation of blood cholesterol at more than one metabolic site and tested to develop effective cholesterol-lowering functional foods and further translated to the human needs. [ABSTRACT FROM AUTHOR]

Arrays of chemical oxidants are produced in healthy cells, where they function as important signaling molecules that are crucial in homeostatic regulation and cellular adaptation. The molecular basis of ˵redox signaling″ is a series of oxido-reductive chemical reactions in which oxidants or reductants post-translationally alter the structure of proteins. These modifications equate to signal sensing events, in which an alteration in protein redox status may couple to a change in its function. This coupling of sensing to function is a true transduction event, allowing conversion of the cellular redox state into altered enzymatic activities. Here we review redox signaling in the cardiovascular system, considering the variety of post-translational oxidative modifications that explain redox sensing and signal transduction by proteins at the molecular level. [ABSTRACT FROM AUTHOR]

The metaphoric concept of oxidative stress has been fundamental to knowledge systematization in the field of redox processes in biomedicine. Oxidative stress has evolved over recent years to account for a disruption of redox signaling and equilibrium, rather than just a plain imbalance between prooxidants and antioxidants causing molecular damage. Redox signaling has been documented as a potent and ubiquitous mode of regulation of several important physiological events, and its dysregulation accounts for disease pathophysiology. However, there are as yet several unclear aspects regarding the mechanisms whereby redox-related intermediates modulate signaling targets at the required level of specificity and robustness. Thus, the redox signaling concept itself is also an evolving entity. The model of ROS-mediated differential regulation of thiol targets solely on the basis of distinct chemical reactivities of thiol groups has not been able to fully account for the variety and sophistication of redox-dependent responses. Thus, current models of redox signaling have to take into account additional hierarchical levels of regulation in the cell biology realm. The notion of compartmentalization is an important example in this direction, and here we have tied it to the systems biology–based idea of modularity. In this context, oxidative stress may be viewed as a disruption of redox modular architecture and the consequent emergence of supramodular secondary signaling. Further contextualizing these mechanisms is essential in order to allow meaningful progress in strategies aiming at improving detection of disrupted redox signaling or redox-related therapeutic interventions. These considerations indicate that, while having lost some its metaphorical strength with respect to mechanistical insights, the dynamically reformulated concept of oxidative stress remains powerful as an operational tool to communicate and contextualize science in the field. [ABSTRACT FROM AUTHOR]

Oxidative stress is defined as an imbalance of the generation of reactive oxygen species (ROS) in excess of the capacity of cells/tissues to detoxify or scavenge them. Such a state of oxidative stress may alter the structure/function of cellular macromolecules that eventually leads to tissue/organ dysfunction. The harmful effects of ROS have been largely attributed to its indiscriminate, stochastic effects on the oxidation of protein, lipids, or DNA. Alternatively, detrimental effects of ROS may be mediated by aberrant ˵redox signaling″ in specific pathophysiologic contexts. Cardiovascular disease is a major cause of morbidity and mortality in industrialized nations. Acute myocardial infarction from atherosclerotic coronary artery disease often results in remodeling responses of the myocardium that may culminate in congestive heart failure. Another important cause of CHF is chronic pressure overload due to systemic hypertension. We discuss mechanisms by which oxidative stress contributes to the pathogenesis of vascular disease, endothelial dysfunction, and cardiovascular fibrosis. Identifying specific pathways for ROS generation and roles in cardiovascular fibrosis could lead to rational design of drugs that promote tissue repair/regeneration, while attenuating the progression of CHF. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization and cellular signaling. Increased ROS production has been implicated in various chronic diseases, including hypertension, atherosclerosis, diabetes and kidney disease. Oxidative stress may be both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other prohypertensive factors, such as salt loading, activation of the renin-angiotensin system and sympathetic hyperactivity. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, and vessels. Compelling evidence indicates the importance of the vasculature in the pathophysiology of hypertension, and therefore much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular and renal ROS is a family of nonphagocytic NAD(P)H oxidases, including the prototypic Nox2 homologue-based NAD(P)H oxidase, as well as other NAD(P)H oxidases, such as Nox1 and Nox4. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase, and uncoupled nitric oxide synthase (NOS). NAD(P)H oxidase-derived ROS is important in regulating endothelial function and vascular tone, and oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, important processes involved in vascular remodeling in hypertension. These findings have evoked considerable interest because of the possibilities that therapies targeted against nonphagocytic NAD(P)H oxidase to decrease ROS generation and/or strategies to increase nitric oxide (NO) availability and antioxidants may be useful in minimizing vascular injury and thereby prevent or regress target organ damage associated with hypertension. [ABSTRACT FROM AUTHOR]

Diabetes has a profound impact on the cardiovascular system, and oxidative stress is likely an important mechanism through which diabetes adversely affects that system. Numerous animal and some human studies support the role of oxidative stress as a unifying hypothesis linking hyperglycemia to distinct cardiovascular pathophysiologic processes. The ultimate mechanism of excess production of ROS in diabetes likely involves multiple enzymatic sources of ROS that are both convergent upon common cellular and molecular targets and interrelated with positive feedback loops occurring between these different enzymatic systems. Particular roles of mitochondrial electron transport chain, Nox family NADPH oxidases, and uncoupled NO synthase(s) have been documented. While the experimental data linking oxidative stress to the cardiovascular complications of diabetes are quite extensive, as is the case in many other settings, there is a lack of convincing data in humans demonstrating a protective effect of antioxidants on diabetic cardiovascular disease. Nonetheless, strategies to reduce disrupted redox cell signaling and oxidative stress may find applicability regarding the treatment and prevention of the cardiovascular complications of diabetes. [ABSTRACT FROM AUTHOR]