血管结构-功能耦合障碍在血管衰老及其演变过程的作用机制及干预策略研究

血管衰老是指血管结构和功能随年龄增加发生退行性变的过程，是全身器官衰老的病理生理基础。但血管衰老及其向心脑血管疾病演变过程的机制尚不清楚。申请人团队前期研究提示神经系统器官退行性变存在结构-功能耦合障碍，进一步发现，衰老疾病演变还存在心-脑跨器官特性。本研究基于前期研究基础，集成多方优势，围绕血管衰老及其向心脑血管疾病演变过程中血管结构-功能耦合障碍作用机制关键科学问题，旨在建立能早期显示血管衰老变化特征的多模态影像学评估体系，从宏观到微观，从大血管到微循环，从模式动物到人群队列，系统化解析衰老血管结构-功能耦合障碍的特征；围绕平滑肌细胞衰老这一血管结构-功能耦合障碍的关键，探讨相应的分子网络机制，以求明确血管衰老及其演进的关键时空节点；整合影像、临床、血液多组学分析，制定早期干预策略。本项目的实施将有望解析血管衰老内在机制，从而延缓血管衰老及其向心脑血管疾病演变进程，旨在实现健康老龄化。

Aging causes multifaceted structural and functional impairment, playing a central role in the pathogenesis of cardio-cerebrovascular diseases. It is crucial to understand the structure, function, and structure-function coupling alterations that occurs in the vascular aging and its evolution to cardio-cerebrovascular diseases. Based on the hypothesis of vascular structure-function coupling dysfunction, this project aims to early display the characteristics of vascular aging and its evolution to cardio-cerebrovascular diseases, from macro- to microcirculation, by establishing a multi-modal molecular imaging system; to explore the molecular mechanisms of vascular structure-function coupling dysfunction in vascular aging from the perspective of autophagy regulation; and to develop novel therapeutic interventions for prevention of age-related vascular pathologies and the its procession to cardiovascular and cerebrovascular diseases using multi-omics analysis.