Molecular Imaging of Collagen in Cardiac Remodelling

胶原蛋白的重塑在心衰、动脉粥样硬化、主动脉瘤夹层、肺和肝纤维化等多种疾病的发病机制中起着至关重要的作用。该项目的目的是研究胶原沉积（纤维化）在心肌梗死（MI）后左心室（LV）重塑和心功能中的作用，以及旨在调节纤维化反应的治疗的潜在影响。该项目将利用市售的i型胶原结合磁共振造影剂和已建立的心肌梗死后重构小鼠模型。同时，我们将开发和评估选择性结合I型或III型胶原蛋白的肽，这些肽可以区分不同类型的胶原蛋白，从而增强我们对疾病进展中胶原蛋白转化的理解。探针可以用放射性同位素标记，用于使用PET/SPECT成像进行生物学研究的初始筛选工具。最有希望的探针可以用钆标记用于MRI实验。所有体内成像实验将辅以离体分析。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了230多万人，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17.5万人经历急性心肌梗死发作，在英国有超过50万人患有心衰。

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.