V ascular remodeling involves changes for the whole-vessel circumference and crucially determines lumen caliber 1 in physio(patho)logical situations, such as shear-stress responses, restenosis postangioplasty, 1-3 or native atherosclerosis. 1,4 Moreover, cellular mechanisms governing conductance vessel remodeling are likely shared by small-vessel remodeling, for example, in hypertension.5 Despite such relevance, mechanisms of vessel remodeling are not well known. The identification of endothelium 6 and nitric oxide 7 dependency of shear-induced remodeling raised possible mediator roles of redox processes, as indeed supported by many subsequent studies. 3,8 We showed previously that superoxide dismutase underactivity favors constrictive remodeling after injury (AI), whereas exogenous replenishment of SOD3(ecSOD) rescued bioactive nitric oxide from inducible NO synthase and normalized vessel caliber by counteracting constrictive remodeling rather than neointimal growth. 3 The randomized clinical trial Multivitamins and Probucol Study showed that the antioxidant probucol significantly prevented restenosis postballoon angioplasty, essentially by preventing constrictive remodeling rather than neointima formation. 9Such redox-responsiveness is in line with the importance of redox pathways in cytoskeletal dynamics 10 and extracellular matrix organization, 11 which are both crucially involved in vessel remodeling. However, molecular determinants of such redox signaling pathways remain unclear.Abstract-Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (≈25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibodycontaining perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to...

Objective To evaluate the impact of IVUS guidance on the final volume of contrast agent utilized in patients undergoing PCI. Background To date, few approaches have been described to reduce the final dose of contrast agent in percutaneous coronary interventions (PCI). We hypothesized that intravascular ultrasound (IVUS) might serve as an alternative imaging tool to angiography in many steps during PCI, thereby reducing the use of iodine contrast. Methods A total of 83 patients were randomized to I) angiography-guided PCI or II) IVUS-guided PCI, both groups treated according to a pre-defined meticulous procedural strategy. The primary endpoint was the total volume contrast agent used during PCI. Patients were followed clinically for an average of 4 months. Results The median total volume of contrast was 64.5 ml (interquartile range [IQR] 42.8 – 97.0 ml; minimum 19 ml; maximum 170 ml) in angiography-guided group vs. 20.0 ml (IQR 12.5 – 30.0 ml; minimum 3 ml; maximum 54 ml) in IVUS-guided group (p<0.001). Similarly, the median volume of contrast / creatinine clearance ratio was significantly lower among patients treated with IVUS-guided PCI (1.0 [IQR 0.6 – 1.9] vs. 0.4 [IQR 0.2 – 0.6] respectively; p<0.001). In-hospital and 4-month outcomes were not different between patients randomized to angiography-guided and IVUS-guided PCI. Conclusions Thoughtful and extensive utilization of IVUS as the primary imaging tool to guide PCI is safe, and markedly reduces the volume of iodine contrast, compared to angiography-alone guidance. The use of IVUS should be considered for patients at high risk for contrast-induced acute kidney injury or volume overload undergoing coronary angioplasty.

Introduction: Intravascular optical coherence tomography (IVOCT) is an in-vivo imaging modality based on the introduction of a catheter in a blood vessel for viewing its inner wall using electromagnetic radiation. One of the most developed automatic applications for this modality is the lumen area segmentation, however on the evaluation of these methods, the slices inside bifurcation regions, or with the presence of complex atherosclerotic plaques and dissections are usually discarded. This paper describes a fully-automatic method for computing the lumen area in IVOCT images where the set of slices includes complex atherosclerotic plaques and dissections. Methods: The proposed lumen segmentation method is divided into two steps: preprocessing, including the removal of artifacts and the second step comprises a lumen detection using morphological operations. In addition, it is proposed an approach to delimit the lumen area for slices inside bifurcation region, considering only the main branch. Results: Evaluation of the automatic lumen segmentation used manual segmentations as a reference, it was performed on 1328 human IVOCT images, presenting a mean difference in lumen area and Dice metrics of 0.19 mm 2 and 97% for slices outside the bifurcation, 1.2 mm 2 and 88% in the regions with bifurcation without automatic contour correction and 0.52 mm 2 and 90% inside bifurcation region with automatic contour correction. Conclusion: This present study shows a robust lumen segmentation method for vessel cross-sections with dissections and complex plaque and bifurcation avoiding the exclusion of such regions from the dataset analysis.

No abstract

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.