PDF(Pubmed)
Abstract：
The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents\' metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.
摘要：
心肌梗死（MI）后的纤维化过程导致心脏功能下降，由于纤维化胶原沉积和造影剂代谢紊乱，在纤维化微环境中清除心脏损伤方面，对常规成像策略构成了重大挑战。为了解决这个问题，我们开发了成像策略。具体来说,我们用胶原酶I联合人血清白蛋白(HSA-C)预处理了心肌纤维化胶原,随后使用靶向转铁蛋白受体1肽(CRT)的光学对比剂(CI,CRT-吲哚菁绿)通过近红外(NIR)荧光成像显示了心脏损伤部位.该策略的关键点是用HSA-C预处理可以减少纤维化组织中的背景信号干扰，同时增强心脏损伤部位的CI摄取，使受伤的心脏组织和正常心肌之间的界限更清晰。我们的结果表明，与非目标人群相比，在靶向组中,通过NIR检测到的标准化心脏损伤荧光强度增加了1.28倍.在靶向组的预处理组中,归一化荧光强度增加1.21倍。这些数据证明了应用靶向TfR1的预处理的纤维化胶原和NIR造影剂来识别心脏损伤部位的铁性凋亡的可行性。其在MI患者管理中的临床价值还需要进一步研究。
