Class III and Class IV the Orphans

Class III receptors form homodimers like class I receptors, but bind direct repeats like Class II receptors. Class IV receptors act as monomers and bind extended core sties. While Class I receptors bind steroid hormones, and Class II receptors bind metabolites of nutrients, no pattern has yet emerged for the ligands of Class III or Class IV nuclear receptors. In fact, most of these receptors are orphans with no potential ligands identified. The strictest definition of an endogenous ligand...

The Lyon Diet Heart Study

The Lyon Diet Heart Study was designed to evaluate the impact of a Mediterranean diet on the risk of cardiovascular mortality in persons at high risk for CHD.8 The diet was based on the 1960 Cretan diet as defined by the Seven Countries Study, but the intervention also included supplementation with margarine rich in alpha-linolenic acid (ALA). Participants were advised to eat more bread, root vegetables, green vegetables, fish, and fruit. In addition, participants were asked to reduce their...

The Link Between Oxidative Stress and Vascular Damage in Diabetes

We currently lack good measures of oxidative stress and oxidative damage in human Type 1 and Type 2 diabetes specific studies to make a definitive decision as to whether oxidative stress is increased in diabetes per se, or in relationship to its vascular complications. Once an appropriate measure, or more likely panel of impairment impairment Fig. 7.1 Schema of risk factors and mechanisms for accelerated atherosclerosis in diabetes Fig. 7.1 Schema of risk factors and mechanisms for accelerated...

Conclusion and Future Directions

The onset and progression of diabetes-related atherosclerosis is likely to involve a wide range of pathogenic mechanisms, including oxidative stress, which as suggested by Brownlee, may have a central role stemming from hyperglycemia hyper-glycemia-induced O2- production by mitochondria. Research has increased our understanding of oxidative stress in general and in diabetes, and its contribution to atherosclerosis and diabetic vascular complications. Well-validated and standardized assays of...

Lipids Oxidation and Cardiovascular Disease

Abstract Blood cholesterol and LDL levels are well-established risk factors for cardiovascular disease and, in particular, coronary heart disease. In recent years, the role of LDL in the pathogenesis of atherosclerosis, the underlying cause of coronary heart disease, has been studied extensively. These studies have highlighted the complexity of atherosclerotic processes and identified oxidative damage and inflammation as important components of the process. In addition, the formation and...

The Pathogenesis of Atherosclerosis and Plaque Instability

Despite the dramatic reduction in cardiac events reported in the lipid lowering trial, a substantial body of evidence from sources as diverse as epidemiology, clinical trials and cell biology suggests that the atherogenesis involves processes far more complex than elevation in serum lipids (Table 1.1). Until the 1980s the central focus of pathologists was the debate over whether coronary thrombosis is a premortem or postmortem event. In the late 1980s, however, coronary angioscopy in...

Oxidized Lipids and Atherosclerosis

Each stage of atherosclerosis involves the formation of oxidized lipids, many of which are bioactive. The lipids in lipoprotein particles and cell membranes provide the substrates for the formation of these bioactive molecules. The oxidized lipids can be a product of interactions with reactive oxygen species or reactive nitrogen species (ROS RNS), or oxidative enzymes and lipids in the vasculature.52-54 The oxidative enzymes include myeloperoxidase, 12 15 lipooxygenase, NADPH oxidase, NADH...

Nuclear Receptors as Potential Therapeutic Targets for Metabolic Diseases

Metabolic syndrome is a collection of obesity-related metabolic dysfunctions, including hyperlipidemia, decreased HDL-c, insulin resistance, hypertension, and atherosclerosis. Given their roles in regulating key metabolic pathways, nuclear hormone receptors are current and prospective drug targets to treat these diseases. One reason for the success of nuclear receptor targeted drugs is their ability to have a robust effect on a pathway due to the regulation of multiple target genes within that...