Atherosclerosis Drug Discovery

Although atherosclerosis is the leading cause of death in the so-called affluent societies, there is presently no drug in our pharmacologic armamentarium against disease to either prevent or reverse this insidious killer and debilitant of human lives. Because of this void the First Brook Lodge Symposium on Anti Atherosclerosis Drug Discovery was convened at Brook Lodge in Augusta, Michigan, August 13-15, 1975. The symposium was sponsored by The Upjohn Company and was international in scope, with investi gators attending from such countries as England, Japan, Belgium, and Italy. The symposium focused on the problems associated with the discovery and evaluation of new drugs effective in preventing or reversing atherosclerosis. The thrust of material is centered around animal models useful as tools in the search and evaluation of new drugs. Broadly categorized, the models are nonhuman primates, rabbits, rodents, quail, and tissue culture. The material is a mix of studies on serum lipids and, more importantly, of studies on the artery, irrespective of serum lipid levels. The prevention of arterial lesions, not reduction of serum lipids, is emphasized. A review of all anti-atherosclerotic agents, with the exception of hypolipidemic agents, is included in this volume of the proceedings of the symposium.

This book provides an overview of the etiology of coronary artery disease and focuses on the main therapies and drug interventions currently available. It highlights drug pharmacology and therapeutic challenges, with a special emphasis on the underlying principles of available therapeutics and the on-going development of drugs for coronary artery disease. The book is divided into eight chapters, the first of which describes the classical mechanism of coronary artery disease and its clinical presentations. Chapter 2 lists the principles of and related evidence on the prevention and treatment of coronary artery disease. This includes diet and lifestyle management, and guidelines for the treatment of acute coronary syndrome and stable coronary artery disease. In turn, Chapter 3 describes revascularization treatments, covering percutaneous coronary interventions, coronary artery bypass grafts and thrombolysis. This chapter also addresses the main therapeutic challenges. The following chapters provide an overview of three major categories of coronary artery disease drugs, which target thrombosis (Chapter 4), lipid metabolism (Chapter 5), and hypertension (Chapter 6). Heart failure constitutes the major health burden in the late stage of coronary artery disease; accordingly, current heart failure therapeutics and related drug pharmacology are described in Chapter 7. In closing, Chapter 8 provides a summary of on-going clinical trials for coronary artery disease drug development and discusses a number of promising areas in which intensive research into new therapeutics is being pursued. Given its scope, the book will be of interest to clinicians, medical students and research scientists, as well as to pharmaceutical professionals who are seeking new therapies and drugs for coronary artery disease and related disorders.

This book is the first authoritative and comprehensive text dedicated to the understanding of how cholesterol triggers vascular inflammation and mechanical injury that leads to heart attacks, strokes as well as other organ and tissue pathology. It includes chapters on the background of cholesterol crystal formation and methods for their detection as well as a description of the physiochemical transformation of metastable ‘liquid’ cholesterol to a solid flat plate crystalloid within the cellular and extracellular environment resulting in volume expansion. Chapters also discusses cholesterol crystals and other crystalloid molecules found in atherosclerotic plaque. In addition, the book examines how cholesterol crystals can induce similar injurious processes in other organs including the retina of the eye to cause blindness, in solid cancers causing further tumor growth and in the brain of patients with Alzheimer’s. And lastly, the book addresses various potential therapeutics that disrupt the physiochemical transformation of cholesterol from a liquid to a solid, inhibit its role in triggering inflammation and tissue injury while ushering a path towards targeted therapies. Cholesterol Crystals in Atherosclerosis and Other Related Diseases will be of interest to cardiologists as well as individuals in various fields of science including crystallography, basic and clinical imaging, cardiac oncology, and drug discovery.

Atherosclerosis is a degenerative condition in which arteries build up deposits called plaques (atheromas) which consist of lipids (mainly cholesterol), connective tissue and smooth muscle cells originating from the arterial wall. Plaques develop quietly over a period of years and are unnoticeable until there is an interruption in the normal flow of blood. Plaques may partially or totally block the blood's flow through an artery. Two things that can happen where plaques occur are: bleeding (haemorrhage) into the plaque; and formation of a blood clot (thrombus) on the plaque's surface. Atherosclerosis affects large and medium-sized arteries. The type of artery and where the plaque develops varies with each person. Atherosclerosis research has witnessed startling progress in recent years, partially due to new drugs as well as to new breakthroughs in molecular medicine.

Atherosclerosis is a degenerative condition in which arteries build up deposits called plaques (atheromas) which consist of lipids (mainly cholesterol), connective tissue and smooth muscle cells originating from the arterial wall. Plaques develop quietly over a period of years and are unnoticeable until there is an interruption in the normal flow of blood. Plaques may partially or totally block the blood's flow through an artery. Two things that can happen where plaques occur are: bleeding (hemorrhage) into the plaque; and formation of a blood clot (thrombus) on the plaque's surface. Atherosclerosis affects large and medium-sized arteries. The type of artery and where the plaque develops varies with each person. Atherosclerosis research has witnessed startling progress in recent years, partially due to new drugs as well as to new breakthroughs in molecular medicine.

Atherosclerosis is a degenerative condition in which arteries build up deposits called plaques (atheromas) which consist of lipids (mainly cholesterol), connective tissue and smooth muscle cells originating from the arterial wall. Plaques develop quietly over a period of years and are unnoticeable until there is an interruption in the normal flow of blood. Plaques may partially or totally block the blood's flow through an artery. Two things that can happen where plaques occur are: bleeding (haemorrhage) into the plaque; and formation of a blood clot (thrombus) on the plaque's surface. Atherosclerosis affects large and medium-sized arteries. The type of artery and where the plaque develops varies with each person. Atherosclerosis research has witnessed startling progress in recent years, partially due to new drugs as well as to new breakthroughs in molecular medicine.

Cardiovascular diseases continue to be the leading cause of death in the - jority of industrialized countries. The most frequent underlying pathology, namely atherosclerosis, and its clinical sequelae, namely coronary heart d- ease, cerebrovascular disease and peripheral artery disease, remain common although for a long time we have been made aware of avoidable or mo- ?able etiological factors such as smoking, fat-rich diet or lack of exercise, and although these adverse lifestyle factors have been extensively addressed by population-wide primary prevention programs. Cardiovascular morbidity and mortality also remain high despite successful anti-hypertensive and lipid lowering drug therapies which help to reduce cardiovascular morbidity and mortality by about 30% in both secondary and tertiary prevention settings. This can partly be explained by the increasing life expectancy and growing p- portionofelderly people,especiallyinEuropeandNorthAmerica. Inaddition, the World Health Organization makes the alarming prediction that probably in response to the spreading of western dietary behavior and lack of exercise resulting in an increasing prevalence of diabetes, dyslipidemia and hypert- sion, cardiovascular diseases rather than infectious diseases will become the most frequent cause of death worldwide. This volume of the Handbook of Experimental Pharmacology entitled “Atherosclerosis” is divided into four parts and intends to give an overview on the pathogenesis of atherosclerosis, established treatment and prevention regimen, and of perspectives for the development of new treatment modalities.