Final Activity Report Summary - NUCLEAR RECEPTORS (Modulation of genetic programs of macrophages in atherogenesis)
The leading cause of death in Europe and the cause of more than half of all mortality in the world developed countries is atherosclerosis and has long been a disease that has puzzled scientist and physicians. Atherosclerotic coronary heart disease is the underlying cause for most heart attacks, and one of the most common causes for congestive heart failure, cardiac arrhythmia, and sudden death due to heart attack. To cure atherosclerosis, we must understand its molecular biology. Knowing the molecular components will provide us a potential way for drug development and pharmacological intervention.
Macrophages, immune system scavengers, guard against disease by ingesting particulate material, including microbes. Macrophages play a key role in atherosclerosis because, under the right conditions, take up oxidized low-density lipoproteins (LDL), which is often referred to as bad cholesterol and become a foam cell. The observation that the PPAR-gamma receptor (Peroxisome Proliferator Activated Receptor) and its obligatory partner the Retinoid X Receptor (RXR) are highly expressed in macrophage foam cells within coronary lesions raising many questions about their potential functions in cardiovascular disease.
This issue is especially relevant given the frequency of cardiovascular complications in subjects with type 2 diabetes, an obesity related disease and the single largest risk factor for heart disease, which now have the option to be treated with drugs that regulate PPAR-gamma activity. Our studies have led important insights into the regulation of inflammatory factors in macrophages, the role of PPAR/RXR in atherogenesis and diabetes type 2, and the potential use of PPAR/RXR ligands for therapeutic purposes.
Macrophages, immune system scavengers, guard against disease by ingesting particulate material, including microbes. Macrophages play a key role in atherosclerosis because, under the right conditions, take up oxidized low-density lipoproteins (LDL), which is often referred to as bad cholesterol and become a foam cell. The observation that the PPAR-gamma receptor (Peroxisome Proliferator Activated Receptor) and its obligatory partner the Retinoid X Receptor (RXR) are highly expressed in macrophage foam cells within coronary lesions raising many questions about their potential functions in cardiovascular disease.
This issue is especially relevant given the frequency of cardiovascular complications in subjects with type 2 diabetes, an obesity related disease and the single largest risk factor for heart disease, which now have the option to be treated with drugs that regulate PPAR-gamma activity. Our studies have led important insights into the regulation of inflammatory factors in macrophages, the role of PPAR/RXR in atherogenesis and diabetes type 2, and the potential use of PPAR/RXR ligands for therapeutic purposes.