Response to comment by Moxon et al.

摘要

We would like to thank Clinical Science for the opportunity to respond to the letter [1] which suggests that while we have been able to show that PTP1B inhibitor, trodusquemine, decreases atherosclerotic plaque size as well as serum triglycerides and cholesterol, that we have not shown that it reverses the plaque size, using in vivo imaging techniques such as MRI scanning or ultrasound. Both Ldrl/ and ApoE/ mouse models are historically, very well characterized mouse models of atherosclerosis that rapidly develop atherosclerotic plaques under high-fat/high-cholesterol dietary conditions. However, we wanted to confirm this in our own hands, using the gold-standard technique of sectioning the aorta and staining with Oil Red O over time. We now present data where we performed our pilot study to determine plaque load in these models, after 8 weeks of high-fat diet (HFD). As expected, at 8 weeks of HFD feeding, there was a well-established plaque deposition (Figure 1A,B). Our reversal study was therefore performed at 8 weeks HFD feeding, using a single injection of trodusquemine We demonstrate in our original article in Figure 5C,D [2], that indeed, we can reverse this established plaque.