New pharmacological agents under clinical investigation for treating disorders of lipoprotein regulation leading to atherosclerosis

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Abstract
Coronary heart disease (CHD), whose primary aetiology is atherosclerosis, is the leading cause of mortality and a major cause of morbidity in the industrialised world [1]. Serum lipoprotein levels are aetiologically related to the risk of atherosclerosis and CHD [2]. The liver and the gastrointestinal system are the major protagonists involved in regulation of lipoprotein biochemical-physiological mechanisms and the development of hypercholesterolaemia. Furthermore, specific lipoprotein receptors are being discovered as targets for pharmacological intervention to correct lipoprotein disorders. Agents that target lipoprotein regulation in the liver, gastrointestinal-biliary and atherosclerotic tissues resulting in improved serum lipoprotein levels and/or control of primary and secondary dyslipidaemic disorders including diabetes, are currently undergoing clinical trials. The most novel promising compounds, after the greatly effective newest HMG-CoA reductase inhibitors, are drugs that affect peroxisome proliferator-activated receptors, PPARalpha and PPARgamma receptors, bile acid transport mechanisms, cholesterol absorption and cholesterol acyltransferase and other biochemical targets of lipoprotein regulation. Current knowledge and ongoing trials with these agents are described here within the boundaries of investigator confidentiality agreements.

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