cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2018.3.10101cardio-116Research ArticleПРАКТИЧЕСКАЯ КАРДИОЛОГИЯ ПРИЛОЖЕНИЕ ДЛЯ ПРАКТИЧЕСКИХ ВРАЧЕЙ КЛИНИЧЕСКИЕ СЕМИНАРЫPRACTICAL CARDIOLOGY SUPPLEMENT FOR PRACTISING PHYSICIANS CLINICAL SEMINARSДисфункциональные липопротЕины высокой плотности: роль в атерогенезе и потенциальные мишени для фосфолипидной терапииDysfunctional High-Density Lipoproteins: Role in Atherogenesis and Potential Targets for Phospholipid TherapyТорховскаяТ. И.TorkhovskayaTatyana I.torti@mail.ruКудиновВ. А.KudinovV. A.noemail@neicon.ruЗахароваТ. С.ZakharovaT. S.noemail@neicon.ruМаркинС. С.MarkinS. S.noemail@neicon.ruФГБНУ «Научно-исследовательский институт биомедицинской химии им. В. Н. Ореховича»Russian Federation2018181120185837383Copyright © Kardiomag, 20182018KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/116

В последние годы резко увеличилось число публикаций, посвященных нарушениям у больных атеросклерозом свойств липопротеинов высокой плотности (ЛВП) - в первую очередь способности акцептировать холестерин (ХС) из макрофагов, лежащей в основе их антиатерогенного действия. Это свойство оценивали ex vivo - по активности выхода ХС из клеток к ЛВП или в сыворотку обследуемых больных. Показана обратная связь ХС-акцепторной активности ЛВП с тяжестью атеросклеротического заболевания или частотой его обострения в течение длительных периодов наблюдения, независимо от концентрации ХС ЛВП. Результаты этих исследований привели к появлению концепции о важности «не только количества, но и качества ЛВП», т. е. их функциональности. В настоящем обзоре рассмотрены пути выведения ХС из клеток (с участием клеточных белков), методические подходы, используемые для выявления дисфункциональных ЛВП, результаты исследований у различных категорий больных. Приведены данные разных авторов по выявлению механизмов нарушений свойств ЛВП путем изучения их состава, включая протеомные и липидомные подходы. Определенных доказанных мишеней для коррекции дисфункциональности ЛВП в настоящее время нет. Единственный фактор, отмечаемый многими авторами, это существенная роль фосфолипидов (ФЛ) ЛВП, уровень которых коррелирует с активностью выведения клеточного ХС. Это позволяет по-новому взглянуть на применявшуюся ранее фосфолипидную терапию атеросклероза. Механизм ее заключается, по-видимому, не в снижении уровня ХС в плазме крови, как ожидалось, а в улучшении антиатерогенных свойств ЛВП. Для практического ее применения необходима разработка принципиально новых композиций с высокой биодоступностью ФЛ, обогащающих ЛВП, нормализуя их способность к выведению ХС из тканей.

In recent years the number of articles on damages of high-density lipoproteins (HDL) properties in patients with atherosclerosis has sharply increased. First, it concerns their ability to accept cholesterol (CH) from macrophages - the basis of antiatherogenic action of HDL. This ability was assessed ex vivo - by activity of cell cholesterol (CH) efflux to HDL or into patient’s serum. In many works inverse relationship was shown between CH acceptor capacity of HDL and severity of atherosclerotic disease or frequency of its exacerbations during long-term observation, independent from HDL CH concentration. This led to the emergence of the concept of importance of “not only HDL quantity but also of their quality”, i. e. functionality. In this review we consider pathways of cellular CH efflux (mainly mediated by cell proteins), methods used for detection of dysfunctional HDL, and results of relevant studies in various categories of patients. These studies directed to identification of mechanisms of damages of HDL properties by means of analysis of their composition, used various approaches including those of proteomics and lipidomics. However, now there are no proven targets for correction of HDL dysfunctionality. The only factor, that is underlined by many authors, is the significance of HDL phospholipids, which level correlates with activity of cellular CH efflux. This allows to take a fresh look at previously used phospholipid therapy of atherosclerosis. Its mechanism is apparently not lowering of plasma CH, as was previously expected, but the improvement of HDL antiatherogenic properties. For its practical usage it is necessary to elaborate principally novel formulations with high bioavailability of phospholipids - for HDL enrichment by phospholipid and thereby normalization of their ability to remove CH from tissues.

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The authors declare that there are no conflicts of interest present.