Assessment of ICAM-1 N-glycoforms in mouse and human models of endothelial dysfunction.

Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms. Whether different ICAM-1 N-glycoforms are expressed in vivo during disease is unknown. In this study, using the proximity ligation assay, we assessed the relative formation of high mannose, hybrid and complex α-2,6-sialyated N-glycoforms of ICAM-1 in human and mouse models of atherosclerosis, as well as in arteriovenous fistulas (AVF) of patients on hemodialysis. Our data demonstrates that ICAM-1 harboring HM or hybrid epitopes as well as ICAM-1 bearing α-2,6-sialylated epitopes are present in human and mouse atherosclerotic lesions. Further, HM-ICAM-1 positively associated with increased macrophage burden in lesions as assessed by CD68 staining, whereas α-2,6-sialylated ICAM-1 did not. Finally, both HM and α-2,6-sialylated ICAM-1 N-glycoforms were present in hemodialysis patients who had AVF maturation failure compared to successful AVF maturation. Collectively, these data provide evidence that HM- ICAM-1 N-glycoforms are present in vivo, and at levels similar to complex α-2,6-sialylated ICAM-1 underscoring the need to better understand their roles in modulating vascular inflammation.

Mechanical assessment of arterial dissection in health and disease: Advancements and challenges.

Arterial dissection involves a complex series of coupled biomechanical events. The past two decades have witnessed great advances in the understanding of the intrinsic mechanism for dissection initiation, and hence in the development of novel therapeutic strategies for surgical repair. This is due in part to the profound advancements in characterizing emerging behaviors of dissection using state-of-the-art tools in experimental and computational biomechanics. In addition, researchers have identified the important role of the microstructure in determining the tissue׳s fracture modality during dissection propagation. In this review article, we highlight a variety of approaches in terms of biomechanical measurements, computational modeling and histological/microstructural analysis used to characterize a dissection that propagates in healthy and diseased arteries. Notable findings with quantitative mechanical data are reviewed. We conclude by discussing some unsolved problems that are of interest for future research.

Non-invasive assessment of elastic modulus of arterial constructs during cell culture using ultrasound elasticity imaging.

Mechanical strength is a key design factor in tissue engineering of arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to sacrifice of a large number of animals. We propose an ultrasound-based non-invasive technique for the assessment of the mechanical strength of engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via 2-D phase-sensitive speckle tracking. Young's modulus was then calculated by solving the inverse problem from the distension and the recorded pulse pressure. The stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements indicated an increase in Young's modulus, and histology confirmed the growth of cells and collagen fibrils in the constructs. The results indicate that ultrasound elastography can be used to assess and monitor non-invasively the mechanical properties of arterial constructs.

Economical technology of creation of cell-free matrix of animal and human arterial vessels.

We present a technology of creation of blood vessel connective tissue framework by 2-3-h vessel perfusion with detergents. The technology ensures effective removal of vascular cells without damaging collagen and elastic fibers. The connective tissue frameworks prepared by this method can the used for restoring blood flow in various vascular pathologies. The presented approach attenuates the damaging effect of treatment on the vascular framework due to maximum simplification and shortening of the duration of treatment and is universal for human and animal vessels.

Assessment of S100 protein expression in the epididymis of juvenile and adult European bison.

In our study, we decided to compare S100 protein expression in the material obtained from the epididymes of 5- and 12-month-old calves, and adult European bison, and to detect any differences in S100 expression according to the animal age and size of the organ examined. We used the epididymes obtained from 6 adult European bison aged 6-12 years, from 6 at the age of 12 months and 6 calves aged 5 months. Immunocytochemical reactions were performed using the avidin-biotinylated-peroxidase (ABC) technique according to HSU. Specific polyclonal rabbit antiserum against bovine S100 protein (Bio Genex Laboratories) at a dilution at 1:400 was applied. We found the expression of S100 protein in endothelial cells of arteries, veins and lymphatic vessels in all the study animals. At the same time, we found no differences in the expression of S100 protein in vascular endothelial cells. Our observations seem to indicate that S100 expression in endothelial cells of European bison epididymis is not correlated with age or maturity of the organ tested. We found S100 protein in smooth muscle cells of arteries and veins in all European bison specimens examined. Interestingly in the current study, in young 5-month-old sexually immature European bison specimens we observed weaker expression of S100 protein in smooth muscle cells of small vessels as compared to the same cell type both in large vessels in these animals and in small vessels in adult specimens.

Cryopreserved arterial allografts in the treatment of major vascular infection: a comparison with conventional surgical techniques.

OBJECTIVE: Recent findings with cryopreserved heart valve allografts in the treatment of infectious endocarditis suggest that the use of cryopreserved arterial allografts may improve the outcome in patients with vascular infections. METHODS: Seventy-two patients with mycotic aneurysms (n = 29) or infected vascular prostheses (n = 43) of the thoracic (n = 26) or abdominal aorta (n = 46) were treated with in situ repair and extra-anatomic reconstruction using prosthetic material (n = 38) or implantation of a cryopreserved arterial allograft (n = 34). Disease-related survival and survival free of reoperation were assessed. Morbidity, cumulative lengths of intensive care, hospitalization, antibiotic treatment, and costs were calculated per year of follow-up. RESULTS: The use of cryopreserved arterial allografts was superior to conventional surgery in terms of disease-related survival (P =.008), disease-related survival free of reoperation (P =.0001), duration of intensive care per year of follow-up (median 1 vs 11 days; range 1 to 42 vs 2 to 120 days; P =.001), hospitalization (14 vs 30 days; range 7 to 150 vs 15 to 240 days; P =.002), duration of postoperative antibiotic therapy (21 vs 40 days; range 21 to 90 vs 60 to 365 days; P =.002), incidence of complications (24% vs 63%; P =.005), and elimination of infection (91% vs 53%; P =.001). In addition, costs were 40% lower in the group treated by allografts (P =.005). CONCLUSIONS: The use of cryopreserved arterial allografts is a more effective treatment for mycotic aneurysms and infected vascular prostheses than conventional surgical techniques.