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Альманах клинической медицины

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КАЛЬЦИФИКАЦИЯ СОСУДОВ, АТЕРОСКЛЕРОЗ И ПОТЕРЯ КОСТНОЙ МАССЫ (ОСТЕОПОРОЗ): НОВЫЕ ПАТОФИЗИОЛОГИЧЕСКИЕ МЕХАНИЗМЫ И ПЕРСПЕКТИВЫ РАЗВИТИЯ МЕДИКАМЕНТОЗНОЙ ТЕРАПИИ

https://doi.org/10.18786/2072-0505-2016-44-4-513-534

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Аннотация

Кальцификация, или эктопическая минерализация, кровеносных сосудов – активный процесс, регулируемый клетками, который получает все большее признание как общий сердечно-сосудистый фактор риска. Эктопическая минерализация артерий часто сопровождается уменьшением плотности костной ткани или нарушением костного обмена с  развитием остеопороза. Последние данные подтверждают связь остеопороза с атеросклерозом, что свидетельствует о  параллельном прогрессировании дегенеративных процессов в этих двух тканях, увеличивающем частоту летальных и нелетальных сердечно-сосудистых событий и повышающем риск переломов. У пациентов с остеопорозом имеется более высокий риск сердечно-сосудистых заболеваний, чем у  лиц со здоровой костной тканью. В артериальной стенке найдено много белков, участвующих в  процессах костеобразования и  костной резорбции. Кальцификация сосудов подразумевает в  большей степени остеогенную и в меньшей – хондрогенную дифференцировку остеобластов и  остеокласто-подобных клеток. Показано, что в  атеросклеротической бляшке также экспрессируются многие регуляторы костеобразования и  костной резорбции, некоторые структурные белки кости, такие как остеопротегерин (OPG) и  лиганд-рецептор активатора ядерного фактора κB (RANKL). После связывания RANKL с RANK происходит активация остеокластов, усиливается костная резорбция и процессы кальцификации сосудов. OPG, белок, гомологичный рецептору активатора ядерного фактора κB (RANK), может связываться с  RANKL, блокируя связывание последнего с RANK, что ведет к угнетению дифференцировки преостеокластов в зрелые остеокласты, снижению способности остеокластов резорбировать минеральный матрикс кости и  кальцификации сосудов. Самые последние данные подтверждают, что катепсин  К  (цистеинпротеаза) может активно разрушать коллаген I и II типов – основной компонент матрикса кости и атеросклеротической бляшки. Эти данные еще больше подчеркивают перспективность использования катепсина К как мишени действия новых молекул для лечения остеопороза и атеросклероза. Таким образом, открытие системы цитокинов RANKL-RANK-OPG и важнейшей роли катепсина К в ремоделировании костной ткани, сосудистой кальцификации и  атеросклероза  – шаг вперед в понимании механизмов развития заболеваний и, возможно, в  разработке новых лекарств двойного действия. Новые препараты для лечения остеопороза и  атеросклероза, способствующие усовершенствованию и повышению эффективности существующих методов лечения,  – это недавно зарегистрированный антагонист лиганда рецептора активатора ядерного фактора κB моноклональное антитело деносумаб и  ингибитор катепсина К  одана-катиб, который в  настоящее время находится в третьей фазе клинических испытаний.

Об авторах

А. Долженко
Галле-Виттенбергский университет имени Мартина Лютера
Германия

д-р мед. наук, профессор, консультант Института молекулярной медицины,

06112, Галле, Дамеровштрассе, 1



Т. Рихтер
Клиника Медиан
Германия

д-р мед. наук, руководитель отделения кардиологии,

04651, Бад-Лаузик, Паркштрассе, 4



С. Сагаловски
Клиника Медиан
Германия

д-р мед. наук, руководитель отделения ортопедии,

04651, Бад-Лаузик, Паркштрассе, 4



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Для цитирования:


Долженко А., Рихтер Т., Сагаловски С. КАЛЬЦИФИКАЦИЯ СОСУДОВ, АТЕРОСКЛЕРОЗ И ПОТЕРЯ КОСТНОЙ МАССЫ (ОСТЕОПОРОЗ): НОВЫЕ ПАТОФИЗИОЛОГИЧЕСКИЕ МЕХАНИЗМЫ И ПЕРСПЕКТИВЫ РАЗВИТИЯ МЕДИКАМЕНТОЗНОЙ ТЕРАПИИ. Альманах клинической медицины. 2016;44(4):513-534. https://doi.org/10.18786/2072-0505-2016-44-4-513-534

For citation:


Dolzhenko A., Richter T., Sagalovsky S. VASCULAR CALCIFICATION, ATHEROSCLEROSIS AND BONE LOSS (OSTEOPOROSIS): NEW PATHOPHYSIOLOGICAL MECHANISMS AND FUTURE PERSPECTIVES FOR PHARMACOLOGICAL THERAPY. Almanac of Clinical Medicine. 2016;44(4):513-534. https://doi.org/10.18786/2072-0505-2016-44-4-513-534

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