Expression of a Functional IL-2 Receptor in Vascular Smooth Muscle Cells.

Many nonlymphoid cell types express at least two, if not all three, subunits of the IL-2R; although, compared with lymphocytes, relatively little is known about how IL-2 affects the function of nonlymphoid cells. The limited information available suggests that IL-2 has a substantial impact on cells such as gastrointestinal epithelial cells, endothelial cells, and fibroblasts. In a previous report from our laboratory, we noted that IL-2 and IL-2Rß-deficient mice lose smooth muscle cells over time, eventually resulting in aneurysmal aortas and ectatic esophagi. This finding, combined with our work showing that IL-2 surrounds vascular smooth muscle cells by association with perlecan, led us to ask whether vascular smooth muscle cells express an IL-2R. Toward this end, we reported the expression of IL-2Rß on human and murine vascular smooth muscle cells. We now report that vascular smooth muscle cells express all three subunits of the IL-2R, and that expression of IL-2Rα varies with vascular smooth muscle cell phenotype. Furthermore, we show that, through a functional IL-2R, IL-2 initiates signaling pathways and impacts vascular smooth muscle cell function. Finally, we demonstrate that IL-2 expression increases upon initiation of conditions that promote intimal hyperplasia, suggesting a mechanism by which the IL-2/IL-2R system may impact this widespread vascular pathology.

Adventitial Collagen Crosslink Reduces Intimal Hyperplasia in a Rabbit Arteriovenous Graft Model.

BACKGROUND: Intimal hyperplasia (IH) is the initial lesion of vein graft failure after coronary artery bypass grafting. The weak venous wall is likely one of the primary reasons for IH after exposure to the arterial environment. We investigate whether adventitial collagen cross-link by glutaraldehyde (GA) reinforces the venous wall and then reduces IH. MATERIALS AND METHODS: Adventitial collagen cross-link by 0.3% GA was performed on the rabbit jugular veins. The degree of cross-link was accessed by tensile test. The jugular vein with or without cross-link was implanted into the carotid artery of rabbit. Vein dilatation at the immediate anastomosis and pathological remodeling of vein graft after 4 wk was assessed. RESULTS: Tensile test indicated that the mechanical property of 3-min cross-linked veins more closely resembled that of the carotid artery. In rabbit arteriovenous graft models, 3-min adventitial collagen cross-link limited overdistension (diameter: 3.24 mm versus 4.65 mm, P < 0.01) at the immediate anastomosis and reduced IH (intima thickness: 78.83 µm versus 140.19 µm, P < 0.01) of vein grafts 4 wk after implantation in the cross-link group as compared with the graft group (without cross-link). Compared with the cross-link group, the expression of proliferating cell nuclear antigen and vascular cell adhesion molecule-1 increased significantly at both the mRNA and protein levels within the graft group (P < 0.01), but the expression of smooth muscle-22α decreased significantly (P < 0.01). CONCLUSIONS: Adventitial collagen cross-link by GA increased the vessel stiffness and remarkably reduced IH in a rabbit arteriovenous graft model.

Comparison of Autologous Vein and Bovine Carotid Artery Graft as a Bypass Conduit in Arterial Trauma.

BACKGROUND: Surgical revascularization is the mainstay treatment in treating most traumatic arterial injuries, and autologous great saphenous vein is widely regarded as the conduit of choice. However, the use of the great saphenous vein may be limited by many factors, and there are little data to guide management in this setting. Bovine carotid artery graft (Artegraft, Inc., North Brunswick, NJ, USA) is a biologic conduit that has been used in select trauma cases at our center. The objective of this study was to review and compare our experience with autologous vein and bovine carotid artery in traumatic arterial injuries requiring bypass or interposition. METHODS: This is a retrospective review of all patients with a traumatic arterial injury repaired with autologous vein or bovine carotid artery graft at a single center between April 2014 and October 2016. Outcomes of interest included differences in duration of ischemia, operative times, patency, limb salvage, graft-related complications, and functional status. RESULTS: Thirty patients were included in this study. Seventeen (57%) injuries were to the lower extremity (LE) and 13 (43%) to the upper extremity. Bovine carotid artery graft was used as a conduit in 12 (40%) cases, while autologous vein was used in 18 (60%) patients. Patients were predominantly male (90%). Mean age was 31 ± 15 years. Comorbidities did not differ significantly between the groups. Mean follow-up duration was 19 ± 13 months. Overall primary patency was 82%: bovine versus autologous vein (78% vs. 85%; P = 0.68). Overall secondary patency was 91%: bovine versus autologous vein (78% vs. 100%; P = 0.16). Overall limb salvage was 90%: bovine versus autologous vein (82% vs. 94%; P = 0.28). When comparing bovine carotid artery graft to autologous vein in LE interventions, primary patency (50% vs. 71%; P = 0.40), secondary patency (75% vs. 100%; P = 0.23), and limb salvage (80% vs. 86%; P = 0.76) did not differ significantly. There were no early or late graft infections with either conduit. There were no significant differences in ambulatory status at discharge by graft type. Overall survival was 100%. CONCLUSIONS: In this series, there is a trend toward improved patency and limb salvage with autologous vein. Autologous vein should be the standard of care for revascularization of traumatic arterial injuries. Bovine carotid artery graft appears be a viable alternative, especially in patients requiring urgent revascularization, that does not significantly compromise patency, limb salvage, or functional outcomes.

Early cannulation of bovine carotid artery grafts (Artegraft) after primary vascular access and fistula revision procedures.

OBJECTIVE: Tunneled dialysis catheter (TDC) use has been associated with increased infectious complications and mortality in hemodialysis-dependent patients. Unfortunately, patients who undergo fistula revisions or creation of a new arteriovenous fistula frequently require a TDC during the postoperative period. Bovine carotid artery grafts (BCAGs) can be used as an early-access dialysis conduit to reduce TDC dependence. This study describes the performance of BCAGs that were cannulated early (<3 days) after implantation and associated clinical outcomes. METHODS: BCAGs were implanted in 63 consecutive dialysis-dependent patients. Patients and dialysis centers were directly provided early cannulation instructions; 31 (49%) patients were cannulated early, and of the 31 patients cannulated early, 21 (68%) were cannulated during the first postoperative day. Early complications, primary patency, secondary patency, and TDC incidence were monitored through clinic visits, hospital records, and phone calls to dialysis centers. RESULTS: The primary patency of BCAGs at 1 year in the early and late cannulation cohorts was 28% and 39%, respectively. The secondary patency of BCAGs at 1 year in the early and late cannulation cohorts was 74% and 77%, respectively. Early complications occurred in 11 (19%) patients who received a BCAG. There were no significant differences in complication rates between early and late cannulation patients. Of the 24 patients who underwent the operation without a pre-existing TDC, only three (13%) required TDC placement during the 30-day postoperative period. CONCLUSIONS: BCAGs can be cannulated early without increased complication rates or a negative impact on midterm patency. Early cannulation of BCAGs obviates the need for a TDC postoperatively in dialysis-dependent patients undergoing primary vascular access or fistula revision procedures.

A prospective randomized study of bovine carotid artery biologic graft and expanded polytetrafluoroethylene for permanent hemodialysis access.

OBJECTIVE: Arteriovenous grafts (AVGs) remain reliable substitutes for permanent hemodialysis access in scenarios that preclude the placement of native arteriovenous fistulas (AVFs). The majority of AVGs are constructed of expanded polytetrafluoroethylene (ePTFE), which is relatively inexpensive and readily available, but synthetic AVGs have poor patency rates. On the other hand, biologic grafts confer an advantage by virtue of their inherent similarity to the native human vasculature. However, evidence to support the current preference of synthetic conduits over biologic grafts in clinical practice is scarce. The aim of this protocol is to propose a contemporary re-evaluation and comparison between ePTFE and bovine carotid artery (BCA) grafts. METHODS: This prospective randomized controlled trial is being conducted at an academic hospital center. A total of 100 patients at least 18 years of age and undergoing AVG placement will be recruited and prospectively randomized into two parallel groups with a 1:1 allocation ratio. Patients eligible to receive AVF and those with a known allergic reaction or history of intolerance to any ePTFE or BCA component will not be included in the study. Moreover, patients with a recent active infection at the site of previous AVG placement and patients with a bleeding disorder, an active malignant disease, or a life expectancy <1 year or who refuse blood transfusion and pregnant women will be excluded. Patients will receive either BCA (experimental) or standard ePTFE grafts (control) in compliance with the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines for AVG creation. Primary end points include primary, primary assisted, secondary, and functional patency at 1 year and 2 years after graft placement. Secondary outcomes include complications (pseudoaneurysms, infections, and steal syndrome) and reintervention rates during the first and second postoperative years. Outcomes will be assessed and documented every 6 months. RESULTS: Once the study is completed, analysis of the data will be performed using univariate methods, and Kaplan-Meier and multivariate Cox proportional regression analyses will be employed to evaluate and to compare outcomes between BCA and ePTFE over time. CONCLUSIONS: The creation of a functional and durable dialysis vascular access is crucial in the treatment of patients with end-stage renal disease and is a challenging quest for vascular surgeons. The proposed study compares the outcomes of synthetic and biologic AVG options in patients who are poor candidates for a native AVF. This will help derive contemporary evidence and improve the care of vascular access patients.

The use of vascular homografts in pediatric small bowel transplantation: Single-center experience over a decade.

Intestinal transplantation in children has evolved with more isolated small intestine transplants being performed compared to combined liver-intestine transplants. Consequently, surgical techniques have changed, frequently requiring the use of vascular homografts of small caliber to revascularize the isolated small intestine, the impact of which on outcomes is unknown. Among 106 pediatric intestine and multivisceral transplants performed at our center since 2003, 33 recipients of an isolated small intestine graft were included in this study. Outcome parameters were thrombotic complications, graft, and patient survival. A total of 29 of 33 (87.9%) patients required arterial and/or venous homografts from the same donor, mainly iliac or carotid artery and iliac or innominate vein, respectively (donor's median age 1.1 years [2 months to 23 years], median weight 10 kg [14.7-48.5]). Post-transplant, there were three acute arterial homograft thromboses and one venous thrombosis resulting in two peri-operative graft salvages and two graft losses. Three of four thromboses occurred in patients with primary hypercoagulable state, including the two graft losses. Overall, at a median of 4.1 years (1-10.2) from transplant, 29 of 33 (88%) patients are alive with 26 of 33 (79%) functioning grafts. The procurement of intact, size-matched donor vessels and the management of effective post-transplant anticoagulation are critical.

Lower Extremity Bypass Using Bovine Carotid Artery Graft (Artegraft): An Analysis of 124 Cases with Long-Term Results.

INTRODUCTION: Although biological grafts have been utilized as a vascular conduit in leg bypass for many years, reports of a bovine carotid artery graft (BCAG) in lower extremity revascularization have been scarce. This study analyzed the outcome of lower leg bypass using BCAG. METHODS: A retrospective review of a prospectively collected database of all patients undergoing lower extremity bypass using BCAG from 2002 to 2017 was performed. Clinical outcomes including graft patency and limb salvage were evaluated. RESULTS: A total of 124 BCAG (Artegraft, North Brunswick, NJ) were implanted in 120 patients for lower extremity revascularization. Surgical indications included disabling claudication in 12%, rest pain in 36%, tissue loss in 48%, and infected prosthetic graft replacement in 3%. Autologous saphenous vein was either inadequate or absent in 72% of patients. BCAG was used in 46 patients (37%) who had a prior failed ipsilateral leg bypass. Distal anastomosis was performed in the above-knee popliteal artery, below-knee popliteal artery, and tibial artery in 30 cases (25%), 32 cases (26%), and 48 cases (39%), respectively. Distal anastomotic patch was created in all tibial artery to allow BCAG-tibial reconstruction. The yearly primary patency rates in 5 years were 86.5, 76.4, 72.2, 68.3, and 67.5%, respectively. The corresponding yearly secondary patency rates were 88.5, 84.7, 82.4, 78.5, and 75.6%, respectively. The limb salvage rate at one year was 83.6% and at five years was 86.2% for patients with critical limb ischemia. Multivariate analysis showed poor runoff score (P = 0.03, 95% CI, 1.3-5.3; OR, 1.6) was independently associated with graft occlusion. CONCLUSION: BCAG is an excellent vascular conduit and provides good long-term results in lower extremity bypass.

Decellularized and Secured Porcine Arteries with NaOH-based Process: Proof of Concept.

BACKGROUND: There is a need for small caliber vascular prosthesis. Synthetic grafts are hindered by thrombogenicity and rapid occlusion. Decellularized matrices could be an alternative. We assessed in vitro and in vivo the biocompatibility of porcine artery treated with a chemical/physical process for decellularization and graft securitization with non/conventional pathogens inactivation. METHODS: Porcine carotid arteries (PCA) were treated. First, biopsies (n = 4/tissue) were performed before/after treatment to assess decellularization (hematoxylin and eosin/-4',6-diamidino-2-phenylindole/DNA/Miller). Second, 5 rats received an abdominal aortic patch of decellularized PCA (DPCA). Four pigs received subcutaneous DPCA implants (n = 2/pig). Half were explanted at day 15 and half at day 30. Finally, 2 pigs received DPCA (n = 2) and polytetrafluoroethylene prosthesis (n = 1), respectively, as carotid interposition. Implants were removed at day 30. Inflammation (CD3 and CD68 immunostaining) calcifications (von Kossa staining), remodeling (hematoxylin and eosin), and vascular characterization (CD31 and alpha-smooth muscle actin immunofluorescent staining) were investigated. RESULTS: Ninety-five percentage of decellularization was obtained without structural deterioration. No death occurred. Low inflammatory reaction was found in the 2 models for DPCA. Acquisition of vascular identity was confirmed in the rodent and porcine models. Similarity between native PCA and DPCA was observed after 30 days. In contrast, polytetrafluoroethylene graft showed severe calcifications, higher CD3 reaction, and higher intimal hyperplasia (P < 0.05). CONCLUSIONS: The physical and chemical process ensures decellularization of carotid porcine arteries and their in vivo remodeling with the presence of an endothelium and smooth-muscle-like cells as well as a low level of inflammatory cells.

Bovine carotid artery xenografts for hemodialysis access.

OBJECTIVE: Bovine carotid artery (BCA) grafts have been described as a possibly superior alternative to expanded polytetrafluoroethylene hemoaccess grafts. However, published experience remains limited, and patency rates for nonautogenous arteriovenous grafts remain unsatisfactory. We report herein the largest published experience with the current generation of BCA grafts for dialysis access and analyze subgroups to determine whether obesity, gender, or prior access surgery influences patency. METHODS: We retrospectively reviewed 134 BCA grafts (Artegraft, North Brunswick, NJ) implanted for hemodialysis access in the upper extremities of 126 patients between January 2012 and May 2015. Patients had a mean of 1.8 prior access operations. Primary, primary assisted, and secondary patency rates were calculated using the Kaplan-Meier method, and longitudinal infection risk was tabulated. Patency differences were calculated using the log-rank method. RESULTS: For the entire group, 1-year primary patency was 32%, primary assisted patency was 49%, and secondary patency was 78%. Ten of 133 grafts (7%) developed infection requiring graft excision between 1 and 9 months after implantation. There was no statistical difference between men and women in primary or secondary patency (P = .88, P = .69). There was no difference in primary patency or secondary patency for patients with body mass index >30 or <30 (P = .85, P = .54). Patients who had a BCA graft as their first access attempt had a higher primary and primary assisted patency than that of patients who had the graft placed after prior access failure (P = .039, P = .024). CONCLUSIONS: This represents the largest published series of BCA grafts for arteriovenous grafts in the modern era. The primary patency of BCA grafts in this series was lower than that reported in a smaller randomized study. However, primary assisted and secondary patency were similar. Infection rates in this series appear to be somewhat lower than polytetrafluoroethylene infection rates reported in the literature. BCA grafts are a satisfactory alternative to expanded polytetrafluoroethylene for hemodialysis access, but larger controlled studies are needed to determine whether superior primary patency previously reported is a reproducible finding.

Bovine carotid artery biologic graft outperforms expanded polytetrafluoroethylene for hemodialysis access.

OBJECTIVE: Arteriovenous grafts remain reliable substitutes for permanent hemodialysis access in patients without a suitable autogenous conduit. Advances in conduit design and endovascular management of access-related complications question the preference for synthetic conduits over biologic grafts in contemporary practice. In this study, we compared outcomes between a bovine carotid artery (BCA) biologic graft and expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis access in a recent cohort of patients. METHODS: This was a single-institution retrospective review of 120 consecutive grafts placed in 98 patients between January 1, 2011, and June 30, 2014. Univariate methods (χ2, analysis of variance, t-test) were used to compare demographic and medical characteristics of patients who received each graft type. Kaplan-Meier, log-rank tests, univariate and multivariate logistic analyses, and Cox regression analyses were used to evaluate patency and graft complications. Outcomes were defined and analyzed according to reporting guidelines published by the Society for Vascular Surgery. RESULTS: Of the 120 grafts studied, 52 (43%) were BCA and 68 (57%) were ePTFE. Successful graft use for dialysis was 96% (95% confidence interval [CI], 90%-100%) for BCA and 84% (95% CI, 74%-93%) for ePTFE (P = .055). Comparing BCA vs ePTFE, estimates for primary patency were 30% vs 43% at 1 year and 16% vs 29% at 2 years (P = .27). Primary assisted patency was 36% vs 45% at 1 year and 24% vs 35% at 2 years (P = .57). Secondary patency was 67% vs 48% at 1 year and 67% vs 38% at 2 years (P = .05). There were no differences in primary (hazard ratio [HR], 0.70; 95% CI, 0.40-1.28; P = .25) and primary assisted (HR, 0.87; 95% CI, 0.46-1.65; P = .67) patency for BCA compared with ePTFE. However, secondary patency was higher for BCA compared with ePTFE (HR, 2.92; 95% CI, 1.29-6.61; P = .01). Graft infection rates during the study period were 15.4% for BCA and 20.6% for ePTFE (P = .47). The significant predictors of graft failure were higher body mass index (HR, 1.06; 95% CI, 1.00-1.11; P = .04) and hyperlipidemia (HR, 2.94; 95% CI, 1.27-6.76; P = .01). CONCLUSIONS: In this study of a recent cohort of patients who received arteriovenous grafts, primary and primary assisted patencies were similar between BCA and ePTFE grafts. However, secondary patency was higher for BCA, indicating better durability for the biologic graft than for ePTFE grafts in patients whose anatomy preclude placement of an arteriovenous fistula.

Enhancement of Nitric Oxide Production Is Responsible for Minimal Intimal Hyperplasia of Autogenous Rabbit Arterial Grafts.

BACKGROUND: Vascular endothelium induces smooth muscle cell (SMC) relaxation mainly mediated by endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF). It has previously been reported that functions of these endothelium factors have been greatly impaired in vein grafts. The present study was undertaken to determine whether the functions of EDNO and EDHF might be altered in artery graft.Methods and Results:In rabbits, the right carotid artery was excised and implanted in its original position as an autogenous graft ("artery graft") and the non-operated left carotid artery served as the "control artery". Histochemical changes, acetylcholine (ACh)-induced effects on the intracellular concentration of Ca2+([Ca2+]i) in endothelial cells, endothelium-dependent SMC hyperpolarization and relaxation, and tissue cGMP content were examined on post-operative day 28. "Artery graft" displayed a minimal amount of intimal hyperplasia. When compared with the "control artery", it exhibited greater ACh-induced, endothelium-dependent relaxation, but the reverse was true when EDNO production was blocked. In the "artery graft" (vs. the "control artery"), basal cGMP content was greater, whereas the [Ca2+]iincrease in endothelial cells and the endothelium-dependent SMC-hyperpolarization induced by ACh were less. CONCLUSIONS: It is suggested that the [Ca2+]i-independent EDNO production covers the loss of function of endothelium-dependent SMC hyperpolarization and minimizes intimal hyperplasia caused by surgical operation in autogenous carotid artery graft.

Bacteria of leg atheromatous arteries responsible for inflammation.

BACKGROUND: Ischaemia of the lower limbs is frequently followed by inflammation and, in advanced cases, necrosis of peripheral tissues. Whether this is caused by arterial hypoperfusion only or by the presence of bacteria in the arterial walI as well remains unclear. The aim of the study was to prove the presence and source of bacteria in arterial specimens and evaluate their chemotactic properties resulting in the formation of periarterial cellular infiltrates. MATERIALS AND METHODS: Bacterial culture and testing for 16sRNA were performed in fragments of popliteal artery harvested from amputated limbs. Carotid artery plaques served as controls. Fragments of arteries were transplanted into scid mice to evaluate their chemotactic activity for macrophages. RESULTS: a) higher prevalence of isolates and 16sRNA in atherosclerotic popliteal than carotid arteries, b) high density of plaque and periarterial infiltrates and mRNA level for pro-inflammatory cytokines in popliteal arteries, c) prevalent microbes were Staphylococcus aureus, S. epidermidis and Enterococci, d) foot skin and arterial bacterial phenotypes and DNA revealed evident similarities, and e) more intensive mouse macrophage accumulation in popliteal than carotid implants into scid mice. CONCLUSIONS: The presence of bacteria in the lower limb arterial wall was documented. They may predispose to inflammation secondary to ischaemic changes.

Decellularization of porcine carotid by the recipient's serum and evaluation of its biocompatibility using a rat autograft model.

Recently, decellularized tissues for organ transplantation and regeneration have been actively studied in the field of tissue engineering. In the decellularization process, surfactants such as sodium dodecyl sulfate (SDS) have been most commonly used to remove cellular components from the tissue. However, the residual surfactant may be cytotoxic in vivo and has been reported to hinder remodeling after implantation. In addition, treatment with surfactants may destroy the important extracellular matrix (ECM) structure that allows the decellularized tissue to function as a scaffold for cells. In this study, decellularized tissues with high biocompatibility were created using the recipient's serum. By immersing a heterogeneous tissue in serum conditioned to activate the complement system and DNase I, its cellular components could be removed. Compared to an SDS-treated graft, the serum-treated graft preserved the native structure of its ECM. When subcutaneously implanted into an isogenic inbred rat, the graft treated with the recipient's serum resulted in less immunorejection than did the SDS-treated graft.

Donor and recipient cell surface colony stimulating factor-1 promote neointimal formation in transplant-associated arteriosclerosis.

OBJECTIVE: Transplant-associated arteriosclerosis manifests as progressive vascular neointimal expansion throughout the arterial system of allografted solid organs, and eventually compromises graft perfusion and function. Allografts placed in colony stimulating factor (CSF)-1-deficient osteopetrotic (Csf1(op)/Csf1(op)) mice develop very little neointima, a finding attributed to impaired recipient macrophage function. We examined how CSF-1 affects neointima-derived vascular smooth muscle cells, tested the significance of CSF-1 expressed in donor tissue, and evaluated the contribution of secreted versus cell surface CSF-1 isoforms in transplant-associated arteriosclerosis. METHODS AND RESULTS: CSF-1 activated specific signaling pathways to promote migration, survival, and proliferation of cultured vascular smooth muscle cells. Tumor necrosis factor-α addition increased CSF-1 and CSF-1 receptor expression, and tumor necrosis factor-α-driven proliferation was blocked by anti-CSF-1 antibody. In a mouse vascular allograft model, lack of recipient or donor CSF-1 impaired neointima formation; the latter suggests local CSF-1 function within the allograft. Moreover, reconstitution of donor or recipient cell surface CSF-1, without secreted CSF-1, restored neointimal formation. CONCLUSIONS: Vascular smooth muscle cells activation, including that mediated by tumor necrosis factor-α, can be driven in an autocrine/juxtacrine manner by CSF-1. These studies provide evidence for local function of CSF-1 in neointimal expansion, and identify CSF-1 signaling in vascular smooth muscle cells, particularly cell surface CSF-1 signaling, as a target for therapeutic strategies in transplant-associated arteriosclerosis.

Establishment of an animal model of vascular restenosis with bilateral carotid artery grafting.

BACKGROUND: Vascular restenosis occurring after CABG is a major clinical problem that needs to be addressed. Vein grafts are associated with a higher degree of stenosis than artery grafts. However, the mechanism responsible for this effect has not been elucidated. We aimed to establish a rabbit model of vascular restenosis after bilateral carotid artery grafting, and to investigate the associated spatiotemporal changes of intimal hyperplasia in carotid artery and jugular vein grafts after surgery. MATERIAL AND METHODS: Twenty adult New Zealand white rabbits (10 males; 10 females), weighing 2.0-2.5 kg, were obtained from the Experimental Animal Center of Southern Medical University, Guangzhou, China (License No.: scxk-Guangdong-2006-0015). We quantitatively analyzed intimal thickness, area, and degree of stenosis in carotid artery and jugular vein bridges. RESULTS: After 8 weeks of a high-fat diet, rabbit carotid arteries showed early atherosclerotic lesions. With increasing time after surgery, carotid artery and jugular vein grafts showed histopathological and morphological changes, including smooth muscle cell migration, lipid deposition, intimal hyperplasia, and vascular stenosis. The degree of vascular stenosis was significantly higher in vein grafts than in artery grafts at all time points - 35.1±6.7% vs. 16.1±2.6% at Week 12, 56.2±8.5% vs. 23.4±3.4% at Week 16, and 71.2±1.3% vs. 25.2±5.3% at Week 20. CONCLUSIONS: Rabbit bilateral carotid arteries were grafted with carotid artery and jugular vein bridges to simulate pathophysiological processes that occur in people after CABG surgery.

Comparison of oversized artery and vein grafts for interpositional pedicle lengthening in rat femoral artery.

Vessel grafting is commonly used for revascularization or pedicle lengthening. Although veins are more commonly used, they can form aneurysms when bridging an arterial gap. This can lead to thrombosis, and the risk is increased when there is a size discrepancy. This study reports the long-term results of arterial lengthening via size discrepant carotid artery and femoral vein grafts in a rat femoral artery model (1:1.5 ratio). A total of 28 rats were used in this study, divided into two groups of 14. By the 21st day, one anastomosis in each group has been found to be thrombosed. Long-term patency rates were the same for both groups (93.3%). Radiologic imaging showed that size match in the carotid artery grafts was excellent despite of slightly fusiform dilatation, but in the vein groups, pronounced aneurismal deformation and distortion in the anastomosis was seen. Histologic analysis revealed that in the arterial grafts, endothelial continuity was smooth and mural inflammation was less than that of the vein grafts. Organized or recanalized mural thrombi were seen in 38.5% in the vein grafts, whereas in arterial grafts there were none.

[Performance effect of rabbit carotid artery treated with decellularization and photo-oxidation].

OBJECTIVE: To analyze and discuss the feasibility of rabbit carotid artery treated with decellularization and photo-oxidation. METHODS: Sixty vascular slices of rabbit carotid artery were divided into a fresh group, a cryopreservation group, a glutaraldehyde group, and a decellularization plus photo-oxidation group 15 in each group. To evaluate the physical properties of all the rabbit carotid arteries by testing heat-shrinking temperature, tensile stress and the max elongation of each group. Then by buliding subcutaneous embedding model in SD rats we evaluated the biological stability and the anti-calcification function property of the above rabbit carotid arteries, and the detection means included HE stain, atomic absorption spectrometry and Von-Kossa calcium salt stain. RESULTS: The heat-shrinking temperature, tensile stress and the max elongation in the cryopreservation group were lower or shorter than those of the other groups and the difference had statistical significance (P<0.05). Although the heat-shrinking temperature and the tensile stress in the decellularization plus photo-oxidation group were lower or shorter than those in the glutaraldehyde group (P<0.05), the max elongation in the decellularization plus photo-oxidation group was much longer than that in the glutaraldehyde group (P<0.05). The rabbit carotid artery treated with decellularization plus photo-oxidation showed lower immunogenicity and better biological stability and better anti-calcification property compared with the other groups. CONCLUSION: Decellularization associated with photo-oxidation is a suitable and novel protocol for small caliber artery allograft with a diameter of less than 6 mm which is unbreakable to mechanical properties and conducive to biological stability, which has a broad prospect.

A technical improvement in retropharyngeal carotid reconstruction.

The carotid-carotid bypass via a retropharyngeal tunnel enables treating proximal occlusions. With reference to two clinical cases, we present a technique that consists of transposition of one of the carotid arteries to contralateral position, avoiding simultaneous clamping of both carotids.

Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ mediates pioglitazone-reduced vascular lesion formation.

OBJECTIVE: Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to decrease vascular lesion formation. However, the critical role of vascular smooth muscle cell (VSMC) PPARγ in vascular lesion formation following transplantation is not well understood. In this study, we investigated the role of VSMC PPARγ-mediated signaling in transplantation-associated vascular lesion formation. METHODS AND RESULTS: Carotid arteries from smooth muscle cell-selective PPARγ knockout (SMPG KO) and wild-type mice were transplanted to CBA/CaJ recipient mice. The recipient mice received a control diet or pioglitazone-containing diet. Pioglitazone reduced vascular lesion formation in transplanted wild-type, but not in SMPG KO carotid arteries. Histological analysis suggested that PPARγ attenuates vascular lesion formation through antiinflammatory signaling, as evidenced by the increase of intimal inflammatory cells and tumor necrosis factor-α expression in SMPG KO allografts. Intravital microscopy revealed increased inflammatory cell rolling and attachment to endothelial cells in small blood vessels of SMPG KO mice following cytokine stimulation. SMPG KO mice, as shown by Western blotting, have elevated vascular cell adhesion molecule-1 (VCAM-1) expression. Furthermore, immunohistochemistry demonstrated SMPG KO allografts have increased VCAM-1. CONCLUSIONS: Loss of PPARγ in VSMC promotes transplantation-associated vascular lesion formation through increased VCAM-1 expression. VSMC PPARγ also mediates pioglitazone-reduced vascular lesion formation.

Flanking recipient vasculature, not circulating progenitor cells, contributes to endothelium and smooth muscle in murine allograft vasculopathy.

OBJECTIVE: The prevailing view assumes that circulating endothelial and smooth muscle progenitor cells participate in allograft vasculopathy (AV), although the seminal studies in the field were not designed to distinguish between circulating and migrating cells of recipient origin. We developed a double-transplantation technique to overcome this problem and reinvestigated the origin of endothelial cells (ECs) and smooth muscle cells (SMCs) in murine AV. METHODS AND RESULTS: Carotid artery segments from BALB/c mice were allografted to apolipoprotein E(-/-) B6 mice with or without a "flanking" isograft interpositioned between the allograft and the recipient artery. Either recipient mice or interpositioned isografts expressed enhanced green fluorescent protein, and consequently, cells migrating into the allograft from the flanking vasculature could easily be tracked and distinguished from recruited circulating cells. Without immunosuppression, allograft donor cells vanished as expected, and AV developed by replacement and accumulation of ECs and SMCs of recipient origin. The double transplantation models revealed that all ECs and SMCs in AV had migrated into the allograft from the flanking vasculature without any contribution from putative progenitor cells in the blood. CONCLUSIONS: Migrating cells from the flanking vasculature, not circulating progenitor cells, are the source of recipient-derived ECs and SMCs in murine AV.