Identification of type IV collagen exposure as a molecular imaging target for early detection of thoracic aortic dissection

Abstract

Thoracic aortic dissection (TAD) is an aggressive and life-threatening vascular disease and there is no effective means of early diagnosis of dissection. Type IV collagen (Col-IV) is a major component of the sub-endothelial basement membrane, which is initially exposed followed by endothelial injury as early-stage event of TAD. So, we want to build a noninvasive diagnostic method to detect early dissection by identifying the exposed Col-IV via MRI.Methods: Col-IV-targeted magnetic resonance/ fluorescence dual probe (Col-IV-DOTA-Gd-rhodamine B; CDR) was synthesized by amide reaction and coordination reaction. Flow cytometry analysis was used to evaluate the cell viability of SMC treated with CDR and fluorescence assays were used to assess the Col-IV targeting ability of CDR in vitro. We then examined the sensitivity and specificity of CDR at different stages of TAD via MRI and bioluminescence imaging in vivo.Results: The localization of Col-IV (under the intima) was observed by histology images. CDR bound specifically to Col-IV-expressing vascular smooth muscle cells and BAPN-induced dissected aorta. The CDR signal was co-detected by magnetic resonance imaging (MRI) and bioluminescence imaging as early as 2 weeks after BAPN administration (pre-dissection stage). The ability to detect rupture of dissected aorta was indicated by a strong normalized signal enhancement (NSE) in vivo. Moreover, NSE was negatively correlated with the time of dissection rupture after BAPN administration (r2 = 0.8482).Conclusion: As confirmed by in vivo studies, the CDR can identify the exposed Col-IV in degenerated aorta to monitor the progress of aortic dissection from the early stage to the rupture via MRI. Thus, CDR-enhanced MRI proposes a potential method for dissection screening, and for monitoring disease progression and therapeutic response.

Efficient Cholera Toxin B Subunit‐Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration

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Targeting Blood-Brain Barrier Leakage for Visualizing, Monitoring, and Evaluating Ischemia Reperfusion Injury with Rus-Tc ^99m Probe

“…The anti-actin antibody (1:1000; Proteintech Group, USA) served as control. The protein bands were visualized with enhanced chemiluminescence reagents (ECL), and the signal densitometry was quanti ed by an observer blinded to the groups of the animals using western blotting detection system (Quantity One, Bio-Rad Laboratories, USA) [28] .…”

Common Injuries and Repair Mechanisms in the Endothelial Lining

“…Endothelial injury is an important pathophysiological step toward atherosclerotic stenosis,[ 80 ] an overhealing reaction of the blood vessels to the injury. [ 81 82 ] Studies have shown that various factors can lead to damage of the endothelium,[ 83 ] including inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, aging, and a deficiency of Vitamin D.[ 84 85 86 87 88 ] However, the exact mechanism of endothelial injury is not yet fully understood.…”