Enhanced TfR1 Recognition of Myocardial Injury after Acute Myocardial Infarction with Cardiac Fibrosis via Pre-Degrading Excess Fibrotic Collagen
by
, , ,
Wenwen Yang
1,2,†,
Yueqi Wang
2,†, 
Hongzheng Li
1,
Feifei Liao
1,
Yuxuan Peng
1,
Aimei Lu
1,
Ling Tan
1,
Hua Qu
1,
Linzi Long
1,* and
Changgeng Fu
1,* 1
Graduate School, China Academy of Chinese Medical Sciences, Beijing 100091, China
2
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2024, 13(4), 213; https://doi.org/10.3390/biology13040213
Submission received: 5 January 2024
/
Revised: 18 March 2024
/
Accepted: 20 March 2024
/
Published: 25 March 2024
(This article belongs to the Special Issue Development of New Optical Techniques and Methods for Basic Biology and Biomedical Applications)
Simple Summary
After myocardial infarction (MI), myocardial tissue undergoes a series of complex biological reactions, among which fibrosis is particularly critical. This process leads to troublesome collagen deposition, which not only affects the normal function of the myocardium but also poses a serious challenge to conventional myocardial injury imaging techniques. Especially in the metabolism of contrast media, the uneven distribution caused by fibrosis greatly reduces the accuracy of imaging. To address this problem, we propose an imaging method for myocardial fibrosis processing after myocardial infarction, aiming to improve the accuracy of myocardial injury imaging. Firstly, a combination of collagenase I and human serum albumin (HSA-C) was used to perform deep clearance of myocardial fibrotic collagen. Collagenase I is an enzyme that specifically acts on collagen fibers and can effectively degrade collagen fibers in the myocardium. However, human serum albumin serves as a carrier to help collagenase better distribute in myocardial tissue. After the successful clearance of fibrotic collagen from the myocardium, optical contrast agents targeting the transferrin receptor were used to precisely localize the damaged myocardium. The expression of the transferrin receptor significantly increased after myocardial injury, so this contrast agent can specifically identify the injured myocardium. This precise localization capability provides an important basis for subsequent imaging techniques. With the use of near-infrared fluorescence imaging, we can precisely track the location of myocardial injury. In the area of myocardial damage, the fluorescence signal is significantly enhanced due to the specific binding of the contrast agent, to achieve accurate tracking of the location of myocardial injury. This pretreatment strategy not only effectively eliminates the background interference caused by contrast agent deposition in fibrotic tissue, but also improves the targeting efficiency of contrast agents in cardiac lesions.
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.
