Nitroxide‐enhanced MRI of cardiovascular oxidative stress

Abstract

BackgroundIn vivo imaging of oxidative stress can facilitate the understanding and treatment of cardiovascular diseases. We evaluated nitroxide‐enhanced MRI with 3‐carbamoyl‐proxyl (3CP) for the detection of myocardial oxidative stress.MethodsThree mouse models of cardiac oxidative stress were imaged, namely angiotensin II (Ang II) infusion, myocardial infarction (MI), and high‐fat high‐sucrose (HFHS) diet‐induced obesity (DIO). For the Ang II model, mice underwent MRI at baseline and after 7 days of Ang II (n = 8) or saline infusion (n = 8). For the MI model, mice underwent MRI at baseline (n = 10) and at 1 (n = 8), 4 (n = 9), and 21 (n = 8) days after MI. For the HFHS‐DIO model, mice underwent MRI at baseline (n = 20) and 18 weeks (n = 13) after diet initiation. The 3CP reduction rate, Kred, computed using a tracer kinetic model, was used as a metric of oxidative stress. Dihydroethidium (DHE) staining of tissue sections was performed on Day 1 after MI.ResultsFor the Ang II model, Kred was higher after 7 days of Ang II versus other groups (p < 0.05). For the MI model, Kred, in the infarct region was significantly elevated on Days 1 and 4 after MI (p < 0.05), whereas Kred in the noninfarcted region did not change after MI. DHE confirmed elevated oxidative stress in the infarct zone on Day 1 after MI. After 18 weeks of HFHS diet, Kred was higher in mice after diet versus baseline (p < 0.05).ConclusionsNitroxide‐enhanced MRI noninvasively quantifies tissue oxidative stress as one component of a multiparametric preclinical MRI examination. These methods may facilitate investigations of oxidative stress in cardiovascular disease and related therapies.

Role of oxidative stress in calcific aortic valve disease and its therapeutic implications

“…Novel imaging modalities that assess the in vivo burden of valvular oxidative stress using redox-sensitive probes may therefore represent important tools. 305 , 306 In addition, larger scale in vitro studies examining roles and sources of ROS in human CAVD will also be necessary given the relatively small number of patients recruited to each of the studies described in this review. These in vitro studies may wish to make use of novel, and more-specific fluorescent ROS probes 307 and ROS-targeting nanotechnologies, 308 , 309 when exploring roles of ROS signalling in human CAVD.…”

TEMPO-conjugated tobacco mosaic virus as a magnetic resonance imaging contrast agent for detection of superoxide production in the inflamed liver

“…[28][29][30] For instance, the reduced form of TEMPO-the hydroxylamine-is MRI silent but, in the presence of O 2 À , can oxidize to its MRI active state (Scheme 1). 31,32 This pattern of reactive signaling makes nitroxide agents a handy tool in detecting a host of ROS for various oxidative stress-induced disease states.…”

“…16,27 Organic radical contrast agents (ORCAs) are redox-active, biocompatible, metal-free, and stable nitroxide molecules that have shown the potential to serve as contrast agents to help visualize ROS activity by turning “on or off.” 28–30 For instance, the reduced form of TEMPO—the hydroxylamine—is MRI silent but, in the presence of O 2 ˙ − , can oxidize to its MRI active state (Scheme 1). 31,32 This pattern of reactive signaling makes nitroxide agents a handy tool in detecting a host of ROS for various oxidative stress-induced disease states.…”

Diagnostic value of myocardial stress detection based on feature tracking MRI in patients with acute myocardial infarction

“…Fat cells can secrete a variety of factors, mediate the local inflammatory response, which is closely related to the development of coronary atherosclerosis (11). Coronary angiography (CAG) is the gold standard for the diagnosis of AMI, but the procedure is traumatic and difficult to repeat in the follow-up of patients.…”