title: Blood atherogenicity as a target for anti-atherosclerotic therapy.
abstract: Atherogenicity of serum taken from patients with coronary heart disease (CHD) is the ability to induce cholesterol deposition in cultured cells, such as vascular smooth muscle cells (VSMCs) from human aortic intima or blood-derived monocytes/macrophages. The discovery of this phenomenon evoked the series of studies of serum components responsible for atherogenic effects, especially serum lipoproteins. A fraction of circulating negatively charged low density lipoproteins (LDL) enriched with disialylated LDL was found in the blood CHD patients. This LDL fraction was prone to multiple modifications including desialylation and oxidation, and had advanced immunogenic and atherogenic properties, resulting in cholesterol accumulation in cultured intimal VSMCs and formation of circulating immune complexes in blood. The analysis of this proatherogenic LDL helped to understand the mechanisms of subclinical stages of atherogenesis, and pointed out the presence of individual susceptibility to atherosclerosis in humans. The practical application of serum atherogenicity phenomenon is the development of cell-based models for the assessment of cardiovascular drugs. The suitability of these models in pharmacological research was supported by the results of atherosclerosis regression studies, evaluation of antiatherogenic properties of various classes of cardiovascular drugs, and elucidating the ways for further development of drugs for direct anti-atherosclerotic therapy.
authors: Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, 15-a 3rd Cherepkovskaya Str., 121552 Moscow, Russia. sobenin@cardio.ru.
authors: Igor A
authors: IA
authors: Sobenin
authors: Dimitry A
authors: DA
authors: Chistiakov
authors: Yuri V
authors: YV
authors: Bobryshev
authors: Alexander N
authors: AN
authors: Orekhov
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy; D018929:Cell Culture Techniques; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*
chemical_list: D000960:Hypolipidemic Agents; D008074:Lipoproteins