Development of Fractalkine-Targeted Nanofibers that Localize to Sites of Arterial Injury

Atherosclerosis is the leading cause of death and disability around the world, with current treatments limited by neointimal hyperplasia. Our goal was to synthesize, characterize, and evaluate an injectable, targeted nanomaterial that will specifically bind to the site of arterial injury. Our target protein is fractalkine, a chemokine involved in both neointimal hyperplasia and atherosclerosis. We showed increased fractalkine staining in rat carotid arteries 24 h following arterial injury and in the aorta of low-density lipoprotein receptor knockout (LDLR-/-) mice fed a high-fat diet for 16 weeks. Three peptide amphiphiles (PAs) were synthesized: fractalkine-targeted, scrambled, and a backbone PA. PAs were ≥90% pure on liquid chromatography/mass spectrometry (LCMS) and showed nanofiber formation on transmission electron microscopy (TEM). Rats systemically injected with fractalkine-targeted nanofibers 24 h after carotid artery balloon injury exhibited a 4.2-fold increase in fluorescence in the injured artery compared to the scrambled nanofiber (p < 0.001). No localization was observed in the non-injured artery or with the backbone nanofiber. Fluorescence of the fractalkine-targeted nanofiber increased in a dose dependent manner and was observed for up to 48 h. These data demonstrate the presence of fractalkine after arterial injury and the localization of our fractalkine-targeted nanofiber to the site of injury and serve as the foundation to develop this technology further.

Initial Experience With the Microvascular Plug in Selective Renal Artery Embolization

Purpose: To evaluate the safety and efficacy of the microvascular plug (MVP) for selective renal artery embolization. Methods: Retrospective review was performed on a cohort of 6 patients undergoing renal artery embolization using the MVP between July 2015 and August 2018. Patients’ demographics, indication for embolization, technical details of the embolization procedure, and clinical events were gathered from the patients’ electronic medical records. Results: The patients underwent selective renal artery embolization with a MVP for iatrogenic vascular injuries (n = 3), traumatic vascular injuries (n = 2), and for elective embolization of an angiomyolipoma (n = 1), in native kidneys (n = 4) or in renal allografts (n = 2). Immediate occlusion of the feeding artery was achieved with 1 MVP device in 4 patients. In 1 patient, a second MVP was needed, and in another patient, additional 0.018-inch microcoils were used to completely occlude the injured artery. Technical success was achieved in all patients. The volume of the resulting renal infarction was estimated less than 5% of the renal volume. No other procedure-related complications occurred. Conclusion: The MVP is a safe and effective device allowing superselective renal artery embolization. Therefore, we recommend the MVP as a valuable embolic in superselective renal artery embolization. Additionally, a single device is sufficient in most cases, potentially reducing the cost, duration, and radiation exposure of the procedure.

Ultrasound monitoring of magnet-guided delivery of mesenchymal stem cells labeled with magnetic lipid–polymer hybrid nanobubbles

Mesenchymal stem cells labeled with positively charged magnetic lipid–polymer hybrid nanobubbles could be tracked for magnet-guided delivery onto the site of an injured artery using ultrasound.

Brachial artery injury in pediatric patients: review of management and outcome in 29 patients

Background: The brachial artery is the most frequently injured artery in the upper extremity due to its vulnerability and commonly it is associated with road traffic accidents and occupational injuries. But brachial artery injury in pediatric age group is not very frequent as in adults and commonly associated with supracondylar fracture of humerus. They may present with or without features of ischemia. Prompt diagnosis and treatment is essential for salvage of limb in established ischemia. Obscure presentation of arterial injury poses challenge in early diagnosis and treatment. Repair of the injured artery in these cases is not clearly recommended. We are presenting a series of 29 pediatric brachial artery injuries and their outcome in our institute over the last 5 years.Methods: Twenty nine pediatric patients with brachial artery injury managed in our institute between 2014 to 2018 are assessed retrospectively for operative procedure and outcome.Results: Supracondylar fracture was the most common cause (55.17%). Ischemic and non-ischemic presentation was noted in 41.37% and 69.63% cases respectively. Artery repair was done in 17 (58.62%) cases. Primary repair and interposition vein graft repair was done 8 and 9 cases respectively. Among the 17 repaired artery good functional outcome with Grade 5/5 muscle power noted in 14cases. Amputation was done in two cases.Conclusions: Good functional recovery may be achieved in segmental injury repair with a vein graft. Though in closed injury without ischemic features artery may not be repaired, full functional recovery is possible due to collateral circulations. Obscure presentation detected and repaired early also has a satisfactory result.

Abstract 349: Fetal Growth Restriction Is A Risk Of Vascular Remodeling

Objects: A number of studies suggest that fetal growth restriction (FGR) promotes a risk of cardiovascular disease and metabolic disorders. However, it has not been well assessed whether FGR would be involved in the exaggeration of vascular remodeling. We investigated the effect of FGR on inflammatory vascular remodeling using cuff- induced vascular injury mouse model. Methods: Dams (C57BL/6J strain mice) were fed with an isocaloric diet containing 20% protein (normal protein; NP) or 8% protein (low protein; LP) from 10 weeks of ages. At the day of delivery, all dams were returned to the NP diet. After weaning, offspring were fed with the NP diet. Vascular injury was induced by polyethylene cuff placement around the femoral artery in offspring at 10 weeks of age. Neointima formation was evaluated by Elastica van Gieson staining 2 weeks after cuff placement. We assessed the following parameters in the femoral arteries prepared one week after cuff placement. Inflammatory cytokine and NADPH oxidase subunit were assessed by RT-PCR. Superoxide anion production, cell proliferation were evaluated by dihydroethidium staining, proliferating cell nuclear antigen (PCNA) staining respectively. p38 mitogen-activated protein kinase (p38MAPK) phosphorylation were evaluated by immunoblot analysis. Results: Birth weight was significantly lower in LP offspring (LPO) compared with NP offspring (NPO); however, LPO showed a similar body weight compared with NPO at 10 weeks of ages. Blood pressure at 12 weeks of age in LPO did not differ from NPO. Neointima formation was more exaggerated in LPO than NPO with enhanced oxidative stress and PCNA index in the injured artery. Expressions of MCP-1, IL-6, IL-1β and TNF-α in the femoral artery were more enhanced in LPO. Moreover, expressions of NADPH oxidase subunits, such as p22phox, p40phox, p47phox, p67phox, gp91phpx, Nox4 and Rac1 in the injured artery were enhanced in LPO than NPO. The phosphorylation level of p38MAPK was more increased in LPO than NPO. Conclusion: FGR led to the enhanced vascular remodeling via enhancement of stress responses such as inflammation and oxidative stress. These results suggest that FGR is a risk of vascular remodeling in the later life after birth.