Đường dẫn truyền tín hiệu của Angiotensin II qua thụ thể AT1: Những hiểu biết mới về cơ chế và bệnh sinh

Clinical Science - Tập 112 Số 8 - Trang 417-428 - 2007
Sadaharu Higuchi1, Haruhiko Ohtsu1, Hiroyuki Suzuki1, Heigoro Shirai1, Gerald D. Frank2, Satoru Eguchi1
1Cardiovascular Research Center, Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
2Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 U.S.A.

Tóm tắt

Đường dẫn truyền tín hiệu nội bào của AngII (angiotensin II) đã được chứng minh có liên quan đến các bệnh tim mạch, chẳng hạn như tăng huyết áp, xơ vữa động mạch và tái hẹp sau chấn thương. Thụ thể AT1 (thụ thể loại 1 của AngII), một thụ thể liên kết với protein G, đóng vai trò trung gian cho hầu hết các tác động sinh lý và bệnh lý của AngII, và thụ thể này chủ yếu được biểu hiện ở các tế bào tim mạch, như tế bào cơ trơn mạch máu (VSMCs). AngII kích hoạt nhiều phân tử tín hiệu khác nhau, bao gồm các chất dẫn truyền thứ cấp từ protein G, kinase protein và protein nhỏ G (như Ras, Rho, Rac, v.v.), thông qua thụ thể AT1 dẫn đến tái cấu trúc mạch máu. Các thụ thể yếu tố tăng trưởng, chẳng hạn như EGFR (thụ thể yếu tố tăng trưởng biểu bì), đã được chứng minh là được kích hoạt qua ‘trans’ bởi thụ thể AT1 trong VSMCs để trung gian cho sự sinh trưởng và di cư. Rho và hiệu ứng của nó là Rho-kinase/ROCK cũng được liên kết với các hoạt động tế bào bệnh lý của AngII ở VSMCs. Ít thông tin hơn được biết đến về tín hiệu AngII ở nội mô; tuy nhiên, các nghiên cứu gần đây gợi ý rằng tín hiệu AngII ở nội mô điều chỉnh tích cực cũng như tiêu cực cho con đường tín hiệu NO (nitric oxide) và do đó, điều chỉnh sự rối loạn chức năng nội mô. Hơn nữa, các protein tương tác với thụ thể AT1 đã được xác định gần đây, có khả năng điều chỉnh đường dẫn truyền tín hiệu AngII và các chức năng bệnh lý của chúng tại các cơ quan mục tiêu. Trong bài tổng quan này, chúng tôi tập trung vào các phát hiện và khái niệm gần đây cho thấy sự tồn tại của các cơ chế tín hiệu mới được đề cập ở trên mà qua đó AngII trung gian cho sự hình thành các bệnh tim mạch.

Từ khóa


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