Molecular Imaging of Collagen in Cardiac Remodelling

胶原重构在心力衰竭、动脉粥样硬化、主动脉瘤夹层、肺和肝纤维化等疾病的发病机制中起着至关重要的作用。本项目的目的是探讨胶原沉积(纤维化)在心肌梗死(MI)后左室(LV)重构和心功能中的作用，以及旨在调节纤维化反应的治疗的潜在影响。该项目将利用商业上可获得的I型胶原结合磁共振造影剂和已建立的心肌梗塞后重塑的小鼠模型。同时，我们将开发和评估选择性地与I型或III型胶原结合的多肽，这些多肽可以区分不同类型的胶原蛋白，从而加强我们对胶原蛋白在疾病进展中周转的理解。这些探针可以被放射性同位素标记，作为使用PET/SPECT成像进行生物学研究的初始筛查工具。然后，最有希望的探针可以被Gd标记，用于核磁共振实验。所有活体成像实验都将得到体外分析的补充。背景：心血管疾病(CVD)包括冠心病、中风、心力衰竭(HF)、心肌病和心房颤动，影响着超过230万人，约占英国所有死亡人数的27%。在所有心血管疾病中，心肌梗死(MI)和心力衰竭是最常见的，每年约有17.5万人经历急性MI，在英国有超过50万人患有心力衰竭。

Remodeling of collagen plays a crucial role in the pathogenesis of several diseases including heartfailure, atherosclerosis, aortic aneurysm dissection, lung and liver fibrosis. The Aim of this project is toinvestigate the role of collagen deposition (fibrosis) on left ventricular (LV) remodeling and cardiacfunction post myocardial infarction (MI) and the potential impact of therapies that aim at modulating thefibrotic response. The project will utilize a commercially available collagen I-binding MR contrast agent and an established murine model of post-MI remodeling. In parallel, we will develop and evaluate peptides that selectively bind to collagen types I or III and which allow discrimination between the different types of collagen and thus enhance our understanding of collagen turnover in disease progression. The probes can be labelled with radioisotopes for initial screening tool in biological studies using PET/SPECT imaging. The most promising probe can then be labelled with gadolinium for MRI experiments. All in vivo imaging experiments would be complemented by ex vivo analysis. BACKGROUND: Cardiovascular diseases (CVD) including coronary heart disease, stroke, heart failure (HF), cardiomyopathy, and atrial fibrillation affect more that 2.3 million people and account for ~27% of all deaths in the UK. Amongst all CVD, myocardial infarction (MI) and heart failure are the most frequent with ~175,000 people experiencing episodes of acute MI per year and more than 500,000 people are living with HF in the UK.