Tăng đường huyết mãn tính và khả dụng nitric oxide đóng vai trò chủ chốt trong các biến đổi mạch máu có khả năng gây xơ vữa

Genes and Nutrition - Tập 2 - Trang 195-208 - 2007
Assunta Pandolfi1, Elena Anna De Filippis2
1Aging Research Center, Ce.S.I., “Gabriele D’Annunzio” University Foundation, Department of Biomedical Science, University of “G. D’Annunzio”, Chieti-Pescara, Italy
2School of Life Sciences, Arizona State University, Tempe, USA

Tóm tắt

Bệnh tiểu đường có liên quan đến việc xơ vữa động mạch gia tăng nhanh chóng, và các biến chứng mạch máu lớn là nguyên nhân chính dẫn đến bệnh tật và tử vong trong bệnh này. Mặc dù hiểu biết của chúng ta về bệnh lý mạch máu đã được cải thiện đáng kể gần đây, nhưng cơ chế dưới đây khiến xơ vữa động mạch gia tăng trong bệnh tiểu đường vẫn chưa được làm rõ. Sự rối loạn chức năng tế bào nội mô đang nổi lên như một thành phần then chốt trong bệnh sinh của những bất thường tim mạch liên quan đến bệnh tiểu đường. Mặc dù đã được xác định rằng nội mô đóng một vai trò quan trọng trong sự duy trì tổng thể của mạch máu, các tế bào cơ trơn mạch máu (vSMC) trong lớp áo nội của động mạch cũng có một vai trò liên quan đến sự phát triển của xơ vữa động mạch trong bệnh tiểu đường. Tuy nhiên, những thay đổi do glucose cao gây ra ở hành vi của vSMC chưa được đặc trưng đầy đủ. Một số nghiên cứu đã báo cáo rằng sự tổng hợp và/hoặc tác động của nitric oxide (NO) thường bị suy giảm trong bệnh tiểu đường và rối loạn chức năng nội mô. Hơn nữa, mặc dù tế bào nội mô là nơi chính thưc hiện tổng hợp NO trong mạch máu, vSMC cũng có biểu hiện của các enzyme tổng hợp nitric oxide (NOSs) và việc tổng hợp NO trong vSMC có thể là quan trọng cho chức năng của mạch máu. Mặc dù đã biết rằng vSMC góp phần vào bệnh lý mạch máu trong bệnh tiểu đường bằng việc thay đổi từ trạng thái nghỉ ngơi sang kiểu hình kích hoạt, tăng sinh và di chuyển (được gọi là mô hình kiểu hình), liệu sự mô hình kiểu hình thay đổi này có thể liên quan đến sự thay đổi trong hệ thống nitrergic hay không vẫn còn gây tranh cãi. Dữ liệu gần đây của chúng tôi cho thấy rằng, trong cơ thể sống, tình trạng tăng glucose mạn tính có thể làm gia tăng số lượng các clone vSMC tăng sinh, các clone này tồn tại trong nuôi cấy và liên quan đến việc tăng biểu hiện và hoạt động eNOS. Tuy nhiên, sự tăng cường eNOS và việc tổng hợp NO tăng lên diễn ra trong điều kiện có sự gia tăng đáng kể đồng thời sản xuất O2−. Vì khả dụng NO sinh học có thể không tăng lên trong vSMC bị kích thích bởi glucose cao, thật hấp dẫn khi giả thuyết rằng kiểu hình tăng sinh quan sát thấy trong các tế bào từ chuột mắc bệnh tiểu đường có liên quan đến sự mất cân bằng redox chịu trách nhiệm cho việc quenching và/hoặc trapping NO, dẫn đến mất khả năng sinh học của nó. Điều này có thể cung cấp cái nhìn mới về các cơ chế chịu trách nhiệm cho sự xơ vữa động mạch gia tăng trong bệnh tiểu đường.

Từ khóa

#Bệnh tiểu đường #xơ vữa động mạch #nitric oxide #tế bào nội mô #tế bào cơ trơn mạch máu

Tài liệu tham khảo

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