Сердечно-сосудистые эффекты семаглутида и тирзепатида и их потенциал в кардиопротекции

Ожирение и сахарный диабет приводят к метаболическим изменениям, которые вызывают морфологические и функциональные трансформации в сердечно-сосудистой системе. Патогенез поражения сердечно-сосудистой системы при ожирении многосторонен. Сердечно-сосудистые осложнения, связанные с ожирением, вызываются процессами с участием гормонов и пептидов, когда включаются воспаление, инсулинорезистентность, эндотелиальная дисфункция, коронарный кальциноз, активация коагуляции, ренин-ангиотензин-альдостероновой и симпатической нервной систем, приводя к развитию сердечной недостаточности как с сохраненной, так и со сниженной фракцией выброса. Инициация эффективных, безопасных и доступных терапевтических интервенций может иметь решающее значение для управления кардиометаболическим здоровьем. Настоящий обзор имеет цель обобщить результаты проведенных исследований, подтверждающих эффективность и безопасность препаратов с инкретиновой активностью: одного из самых назначаемых препаратов из класса агонистов рецепторов глюкагоноподобного пептида 1 семаглутида и первого двойного агониста рецепторов глюкозозависимого инсулинотропного полипептида/глюкагоноподобного пептида 1 тирзепатида. Подробно рассмотрены патогенетические механизмы поражения сердечно-сосудистой системы при ожирении на основании последних фундаментальных исследований и механизмы, реализуемые в сердце и сосудах глюкагоноподобным пептидом 1 и глюкозозависимым инсулинотропным полипептидом. Акцент делается на возможностях инкретиномиметиков, помимо гипогликемического действия, снижать воспаление сосудистой стенки, массу жировой ткани и способствовать улучшению липидного профиля, что проявляет их метаболизм-модифицирующие качества. При этом инкретины могут быть отнесены к препаратам болезнь-модифицирующей терапии, поскольку воздействуют на сердечно-сосудистую систему, улучшая функциональное состояние эндотелия, снижая артериальное давление, замедляя агрегацию тромбоцитов, ингибируя апоптоз кардиомиоцитов, улучшая утилизацию глюкозы и оказывая вазодилатирующее действие. Это объясняет наблюдаемое в клинических исследованиях снижение риска сердечно-сосудистых осложнений, а в экспериментальных исследованиях – уменьшение зоны некроза при моделировании инфаркта миокарда и применении инкретиномиметиков.

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