Non-invasive in vivo imaging of changes in Collagen III turnover in myocardial fibrosis

Nadia Chaher, Sara Lacerda, Giuseppe Digilio, Sergio Padovan, Ling Gao, Begoña Lavin, Rachele Stefania, Carlos Velasco, Gastão Cruz, Claudia Prieto, René M. Botnar, Alkystis Phinikaridou
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Abstract

Heart failure (HF) affects 64 million people globally with enormous societal and healthcare costs. Myocardial fibrosis, characterised by changes in collagen content drives HF. Despite evidence that collagen type III (COL3) content changes during myocardial fibrosis, in vivo imaging of COL3 has not been achieved. Here, we discovered the first imaging probe that binds to COL3 with high affinity and specificity, by screening candidate peptide-based probes. Characterisation of the probe showed favourable magnetic and biodistribution properties. The probe’s potential for in vivo molecular cardiac magnetic resonance imaging was evaluated in a murine model of myocardial infarction. Using the new probe, we were able to map and quantify, previously undetectable, spatiotemporal changes in COL3 after myocardial infarction and monitor response to treatment. This innovative probe provides a promising tool to non-invasively study the unexplored roles of COL3 in cardiac fibrosis and other cardiovascular conditions marked by changes in COL3.

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对心肌纤维化过程中胶原蛋白 III 更替变化的无创活体成像
心力衰竭(HF)影响着全球 6400 万人,造成巨大的社会和医疗成本。以胶原蛋白含量变化为特征的心肌纤维化是心力衰竭的诱因。尽管有证据表明 III 型胶原蛋白(COL3)的含量在心肌纤维化过程中会发生变化,但 COL3 的体内成像尚未实现。在这里,我们通过筛选候选肽基探针,发现了第一个能与 COL3 高亲和力和特异性结合的成像探针。探针的表征显示出良好的磁性和生物分布特性。我们在小鼠心肌梗塞模型中评估了该探针用于体内分子心脏磁共振成像的潜力。利用这种新探针,我们能够绘制和量化心肌梗塞后 COL3 的时空变化图,并监测对治疗的反应。这种创新探针为非侵入式研究 COL3 在心脏纤维化和其他以 COL3 变化为标志的心血管疾病中尚未探索的作用提供了一种前景广阔的工具。
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