ПАТОФИЗИОЛОГИЧЕСКАЯ ЗНАЧИМОСТЬ МОЛЕКУЛЯРНОЙ ГЕТЕРОГЕННОСТИ ЭНДОТЕЛИАЛЬНЫХ КЛЕТОК

Основные положения

• Приобретение и поддержание тканеспецифичности ЭК зависит от биомеханических воздействий, биохимических параметров циркулирующей крови, молекулярных сигналов от других клеточных популяций и от компонентов внеклеточного матрикса, а также от патологических процессов в окружающих тканях.
• В силу широкого спектра возможной специализации эндотелиальные клетки капилляров обладают наиболее выраженной гетерогенностью и имеют наибольший потенциал молекулярной пластичности.
• Гетерогенность различных типов эндотелиальных клеток in vivo очевидна, однако молекулярная гетерогенность эндотелиальных клеток артерий, вен и сосудов микроциркуляторного русла in vitro и ее патофизиологическая значимость остаются неясными.

Резюме

В данном обзоре анализируется молекулярная гетерогенность эндотелиальных клеток (ЭК) различных направлений дифференцировки и различной анатомической локализации и рассматривается ее патогенетическая значимость. Последние исследования с использованием секвенирования одиночных клеток продемонстрировали выраженную молекулярную гетерогенность ЭК в физиологических и патологических условиях функционирования организма, при этом молекулярная гетерогенность ЭК различных направлений дифференцировки ниже таковой в различных органах, а гетерогенность ЭК кровеносных сосудов выше, чем лимфатических. Приобретение и поддержание тканеспецифичности ЭК зависит от нескольких основных факторов: 1) характерного для того или иного органа биомеханического воздействия (параметров напряжения сдвига, циклического растяжения сосудов и плотности внеклеточного матрикса); 2) биохимических параметров циркулирующей крови (газового состава и концентрации различных молекул); 3) юкстакринных и паракринных молекулярных сигналов от других клеточных популяций в составе органа и от компонентов внеклеточного матрикса; 4) патологических процессов внутри самого органа (в особенности воспаления, гипоксии или фиброза). В силу широкого спектра возможной специализации, оптимальной для нужд того или иного органа, именно ЭК капилляров обладают наиболее выраженной гетерогенностью и имеют наибольший потенциал молекулярной пластичности. В то время как ЭК капилляров не имеют общих маркеров, менее пластичные ЭК вен и ЭК артерий имеют относительно специфичные маркеры дифференцировки в эмбриональном периоде (транскрипционный фактор COUP-TFII и рецептор B-типа к эфрину 4 (EPHB4) в ЭК вен; транскрипционные факторы сигнального пути Notch HEY1, HEY2 и HES1, белки щелевых межклеточных контактов GJA4 и GJA5, семафорин 3G (SEMA3G) и эфрин B2 (EFNB2) в ЭК артерий). Вопрос о наличии и степени выраженности молекулярной гетерогенности различных типов ЭК in vitro, а также ее патофизиологической значимости в отсутствие характерных для организма биофизических и биохимических факторов остается открытым.

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