Роль рецепторов ЛНП в развитии атеросклероза

Роль рецепторов ЛНП в развитии атеросклероза стала вырисовываться после того, как было показано, что их отсутствие ведет к тяжелому заболеванию, названному семейной гипер- холестеролемией. В 1939 г. К. Мюллер из Общественной больницы в Осло (Норвегия) идентифицировал это заболевание как врожденное нарушение метаболизма, приводящее к высокому содержанию холестсрола в крови и к поражению сердца в молодом возрасте. Он выяснил, что болезнь передается как доминантный признак, контролируемый одним геном. В 60-х годах А. Хачадурян из Американского университета в Бейруте и Д. Фредриксон из Национального института заболеваний сердца и легких (США) показали, что существуют две формы заболевания: гетерозиготная и более тяжелая

гомозиготная. Гетерозиготы, т.е. те, кто унаследовал только один мутантный ген, встречаются сравнительно часто — в большинстве этнических групп примерно 1 человек на 500. У них концентрация ЛНП в плазме крови вдвое выше нормы (даже в период пренатального развития) и сердечные приступы начинаются уже к 35 годам. Среди лиц 60-летнего возраста, страдающих ишемической болезнью сердца, каждый 20-й гетерозиготен по признаку семейной гиперхолестеролемии.

Если оба супруга гетерозиготны по признаку семейной гнперхолестероле- мии (такие браки встречаются с частотой 1:250 тыс.), каждый их ребенок с вероятностью 1:4 «получит в наследство» сразу две копии мутантного гена, по одной от каждого родителя. У таких гомозигот (они встречаются с частотой 1:106) концентрация циркулирующих ЛНП более чем в 6 раз превышает норму, так что поражение сердца может развиться у них уже в 2 гола и становится практически неизбежным к 20-летнему возрасту. Примечательно, что у этих детей кроме повышенного содержания циркулирующих ЛНП нет ни одного из прочих факторов риска атеросклероза. У них нормальное кровяное давление, они не курят и концентрация глюкозы в крови нормальная. Гомозиготы по признаку семейной гиперхолестеролемии — это поставленный самой природой эксперимент, который однозначно указывает на причинно-следственную связь между повышением концентрации циркулирующих ЛНП и развитием атеросклероза.

Но каков же механизм повышения содержания ЛНП?

 

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