Генетические факторы риска сосудистого старения: молекулярные механизмы, полиморфизм генов-кандидатов и генные сети

Возраст считается независимым и решающим фактором риска в развитии сердечно-сосудистых заболеваний. Старение клеток сосудов индуцирует сложные изменения структуры и функций сосудистой сети. В статье рассматривается ряд молекулярно-генетических механизмов, участвующих в патогенезе сосудистого старения: клеточная и митохондриальная дисфункция, дисфункция эндотелия, истощение пула прогениторных клеток, укорочение и повреждение теломер, хроническое воспаление, окислительный стресс, нарушение регуляции сосудистого тонуса. Появляются всё новые подтверждения перекрестной вовлечённости в процессы сосудистого старения генов-кандидатов, ассоциированных с продолжительностью жизни и сердечно-сосудистыми заболеваниями, например, таких как ACE, SIRT1, TERC, FOXO1, FOXO3, APOE, NOS3. Для 26 генов, участвующих в представленных молекулярных механизмах сосудистого старения, приведены сайты функциональных полиморфизмов. Понимание основных вызванных возрастом патофизиологических изменений в сосудистой стенке дает возможность выбора превентивной стратегии. В заключение обсуждаются современные подходы для лучшего прогнозирования генетического риска на примере визуализации сети генов сосудистого старения.

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