Rabbit Arteries Research Articles

A novel animal model for vulnerable atherosclerotic plaque: dehydrated ethanol lavage in the carotid artery of rabbits fed a Western diet.

The study of unstable atherosclerotic plaques is limited by the absence of ideal animal models to reproduce the plaque instability observed in humans. In this study, we attempted to develop a novel animal model for vulnerable atherosclerotic plaques using dehydrated ethanol lavage in rabbits fed a Western diet (WD). A total of 30 New Zealand White (NZW) rabbits were randomized to 5 groups, including a control group with or without WD, a balloon injury with WD group, and an ethanol injury with or without WD group. Operations were conducted using the right common carotid artery as the target vessel. All animals were followed up for 3 months unless a vascular event occurred. Blood samples and carotid artery specimens were ultimately collected for analysis of atherogenesis. Compared to rabbits in which lesions were induced by balloon injury, those subjected to an ethanol lavage with high cholesterol diet showed progressive atherosclerotic lesions in all carotid artery segments, which were characterized by greater plaque burden, smaller minimum lumen area (MLA), and increased vulnerability as indicated by abundant macrophages, scattered smooth muscle cell (SMC) composition, higher matrix metalloproteinase-9 (MMP-9) expression in plaques, thinner fibrous cap thickness, and higher possibility of stroke event (50% vs. 0%). Meanwhile, the serum interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) levels in the ethanol injury group with a high-cholesterol diet were significantly higher than those in the balloon injury group after 3 months (all P<0.01). We successfully established a novel animal model for vulnerable atherosclerosis by ethanol exposure of the carotid segment that has a higher predictive value for the probability of ischemic events than the balloon injury model. Therefore, it may represent a promising animal model for investigating new therapeutic approaches, novel imaging modalities, and underlying mechanisms for vulnerable atherosclerotic plaque.

Comparative anatomy of dissected optic lobes, optic ventricles, midbrain tectum, collicular ventricles, and aqueduct: evolutionary modifications as potential explanation for non-tumoral aqueductal anomalies in humans

PurposeAn extensive literature has postulated multiple etiologies for aqueductal stenosis. No publications were found, discussing that evolutionary modifications might explain aqueductal anomalies. This study’s objectives were to review the evolutionary modifications of vertebrates’ tectum structures that might explain human aqueduct anomalies. Undertaking vertebrate comparative study is currently not feasible in view of limitations in obtaining vertebrate material. Thus, vertebrate material collected, injected, dissected, and radiographed in the early 1970s was analyzed, focusing on the aqueduct and components of the midbrain tectum.MethodsPhotographs of brain dissections and radiographs of the cerebral ventricles and arteries of adult shark, frog, iguana, rabbit, cat, dog, and primate specimens, containing a barium-gelatin radiopaque compound, were analyzed focusing on the aqueduct, the optic ventricles, the quadrigeminal plate, and collicular ventricles. The anatomic information provided by the dissections and radiographs is not reproducible by any other radiopaque contrast currently available.ResultsDissected and radiographed cerebral ventricular and arterial systems of the vertebrates demonstrated midbrain tectum changes, including relative size modifications of the mammalian components of the tectum, simultaneously with the enlargement of the occipital lobe. There is a transformation of pre-mammalian optic ventricles to what appear to be collicular ventricles in mammals, as the aqueduct and collicular ventricle form a continuous cavity.ConclusionsThe mammalian tectum undergoes an evolutionary cephalization process consisting of relative size changes of the midbrain tectum structures. This is associated with enlargement of the occipital lobe, as part of overall neocortical expansion. Potentially, aqueductal anomalies could be explained by evolutionary modifications.

Injectable Hydrogel Capable of In Situ Covalent Crosslinking for Permanent Embolization.

Vascular embolization provides an effective approach for the treatment of hemorrhage, aneurysms, and other vascular abnormalities. However, current embolic materials, such as metallic coils and liquid embolic agents, are limited by their inability to provide safe, consistent, and controlled embolization. Here, we report an injectable hydrogel that can remain at the injection site and subsequently undergo in situ covalent crosslinking, leading to the formation of a dual-crosslinking network (DCN) hydrogel for endovascular embolization. The DCN hydrogel is simple to prepare, easy to deploy via needles and catheters, and mechanically stable at the target injection site, thereby avoiding embolization of nontarget vessels. It possesses efficient hemostatic activity and good biocompatibility. The DCN hydrogel is also clearly visible under X-ray imaging, thereby allowing for targeted embolization. In vivo tests in a rabbit artery model demonstrates that the DCN hydrogel is effective in achieving immediate embolization of the target artery with long-term occlusion by inducing luminal fibrosis. Collectively, the DCN hydrogel provides a viable, biocompatible, and cost-effective alternative to existing embolic materials with clinical translation potential for endovascular embolization.

Abstract 11653: Intravascular Targeted Photoactivation Guided by Optical Coherence Tomography-Near Infrared Fluorescence (OCT-NIRF) Imaging Promotes Stabilization of Atherosclerotic Plaques

Introduction and Hypothesis: Photoactivation has emerged as an innovative therapeutic strategy for coronary high-risk plaque without metallic remnants, however, limited targetable ability of photoactivator and lack of imaging guidance hinders its application to clinics. To solve these unmet needs, we developed intravascular photoactivation strategy guided by dual-modal OCT-NIRF structural-molecular imaging using a novel theranostic NIRF-emitting photoactivator. Methods and Results: Photoactivatable NIRF-emitting theranostic agent targeting scavenger receptors on macrophages was newly synthesized. The intravascular photoactivation system based on fiber type cylindrical diffuser was newly fabricated for the therapeutic light delivery to the plaques. Forty-eight hours after intravenous injection of scale-up NIRF-emitting photoactivator (equivalent Ce6 dose of 2 mg/kg), OCT-NIRF imaging was able to exactly identify the highly inflamed targets in OCT-delineated plaques of rabbit arteries. Two weeks after therapeutic light irradiation through the catheter to the NIRF enhanced macrophages, the inflammatory NIRF signals of targeted atheroma markedly decreased as compared to the controls (Figure). By comprehensive immunofluorescence analysis, photoactivation produced a prominent increase in macrophage-associated apoptotic bodies and also induced autophagy with an enhanced efferocytosis, resulting in stabilization of the atheroma. Conclusions: Intravascular photoactivation using targeted NIRF emitting photosensitizer could stabilize the inflamed plaque under the guidance of OCT-NIRF imaging. This imaging guided therapeutic innovation will be a promising theranostic strategy for the high-risk coronary plaques.

Reduced Function of Endothelial Nitric Oxide and Hyperpolarization in Artery Grafts with Poor Runoff

BackgroundThe endothelium regulates vascular tonus by releasing nitric oxide (endothelium-derived nitric oxide, EDNO) and hyperpolarizing factor (endothelium-derived hyperpolarizing factor, EDHF). In vein grafts with poor runoff, lack of function of these factors causes severe intimal hyperplasia. This study evaluated how the functions of EDNO and EDHF are altered in artery grafts under poor runoff conditions. Materials and MethodsThe right common carotid arteries of rabbits were excised and implanted in their original positions as autogenous grafts under normal runoff conditions (“nonoccluded grafts”) or poor runoff conditions (“poor runoff grafts”). Histochemical changes, acetylcholine (ACh)-induced effects on endothelium-dependent relaxation and smooth muscle cell (SMC) hyperpolarization were examined. ResultsBoth artery graft types displayed negligible intimal hyperplasia. In the absence and presence of an EDNO synthase inhibitor, ACh-induced relaxation was lower in grafts with poor runoff than in nonoccluded grafts. Furthermore, ACh-induced but not nonreceptor agonist A23187-induced SMC hyperpolarization was lower in the poor runoff graft group than in the nonoccluded graft group. ConclusionsUnlike in those in vein grafts, the functions of EDNO and EDHF in autogenous carotid artery grafts under poor runoff conditions were reduced but partly maintained. In such artery grafts, intimal hyperplasia caused by surgical operation was not present. These results may explain some of the mechanisms underlying the improved patency of artery grafts compared with vein grafts.

Experimental Study of the Effects of Changes in Arteriovenous Pressure Difference on the Survival Area of a Reverse Island Flap

In this article, the effect of the change of arteriovenous pressure on the survival area of reverse island flap was studied. The vein and saphenous artery in rabbits were selected to design the reverse island flap experimental model. Rabbits were divided into 4 groups: A: Control Group; B: Part anastomosis of the saphenous artery group; C: Part anastomosis of the vein group; and D: No superficial veins group. After surgery, for all four groups, flaps were assessed by general observation, radionuclide scans for the survival rate, and histology. We found that the survival rate of flaps in Group B was overtop than the other three groups (P &lt; 0.05). The radioactive material (RM) in group B could be seen clearly, whereas the RM in Groups A, C, and D existed transiently. At ten days post-operation. Group B had more capillary regeneration and blood cells contrast to the other three groups. Increasing blood supply can improve the survival rate of flaps, but simply promoting venous return has no significant effect on improving the survival rate of flaps.

Fabrication of Fe3O4@PVA microspheres by one-step electrospray for magnetic resonance imaging during transcatheter arterial embolization

Magnetic resonance imaging (MRI) has attracted increasing attention as a feasible alternative or adjunctive imaging modality for X-ray digital subtraction angiography because of the high tissue resolution and non-ionization radiation. In this study, a one-step electrospray method was developed to fabricate PVA microspheres encapsulated with in situ synthesized Fe3O4 nanoparticles. Fe3O4@PVA microspheres were mono-dispersed black spheres with a wide range of sizes (262–958 µm). The in situ-synthesized Fe3O4 nanoparticles were used as the contrast agent of MRI and the cross-linkers of PVA matrixes for the embolization purpose. In vivo evaluation of renal arteries of normal rabbits showed that Fe3O4@PVA microspheres had good embolic effect and enhanced capability of MRI. In vitro and in vivo biosafety assessment confirmed that Fe3O4@PVA microspheres had favorable biocompatibility. The DOX-loaded Fe3O4@PVA microspheres showed a typical drug-sustained release profile. These results suggest that the prepared DOX-loaded Fe3O4@PVA microspheres have the function of MRI, embolotherapy and chemotherapy. We expect our study could provide a simple and useful approach for the systematic design, fabrication, and application of a new type of magnetic microspheres as a triple-functional embolic agent for the development of MRI-guided TACE. Statement of significanceDue to the low tissue resolution and hazardous ionization radiation of X-ray digital subtraction angiography, it is beneficial to study MR imaging embolic microspheres for the development of MRI-guided TACE. In this study, a one-step electrospray method was firstly developed to fabricate PVA microspheres encapsulated with in situ synthesized Fe3O4 nanoparticles. Then, chemotherapeutic agent (DOX), contrast media of MRI (Fe3O4) and embolic agent (PVA matrix) were combined together in one body (DOX-loaded Fe3O4@PVA microspheres) to achieve the triple effects of chemotherapy, MR imaging and embolization. This triple-functional embolic agent offers potential for the future development of MRI-guided TACE.

Anticoagulant Hydrogel Tubes with Poly(ɛ-Caprolactone) Sheaths for Small-Diameter Vascular Grafts.

Small-diameter vascular grafts (inner diameter<6mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(ε-caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.

Mechanism of anti-proteins adsorption behavior on superhydrophobic titanium surface

Comprehensively understanding the albumin and fibrinogen adsorption behaviors is of fundamental significance for blood-contacting devices to effectively prevent the proteins adsorption. First, a controllable superhydrophobic surface presented great repellence to different liquids with water contact angle 165.2°, plasma contact angle 154.8° and blood contact angle 152.1°. Secondly, the albumin and fibrinogen adhesion tests indicated that the pure titanium surface was fully covered by the proteins layer while only a small amount of the proteins adhered to the superhydrophobic surface. Furthermore, the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) model was built by considering the Lifshitz-van der Waals (LW), the Lewis acid-base (AB) and the electrostatic double-layer (EL) interactions, the positive value of total interaction energy profile suggested that an overall repulsive interaction between the protein molecules and superhydrophobic surface happened at a small separation distance. Finally, the hollow tubes with inner superhydrophobic surface were implanted into carotid artery of rabbits for two weeks. The content of N element measured by EDS mapping provide a new evidence that superhydrophobic surface owns a great resistance of the proteins absorption, and no thrombosis or blood cells adhered to the superhydrophobic surface. This research revealed the mechanism that superhydrophobic modification could effectively prevent the adsorption of plasma proteins, which could provide some theoretical basis to help design the blood-contacting devices with great hemocompatibility.

In Vivo Blood-Repellent Performance of a Controllable Facile-Generated Superhydrophobic Surface.

Fabrication of a blood-repellent surface is essential for implantable or interventional medical devices to avoid thrombosis which can induce several serious complications. In this research, a novel micropatterned surface was fabricated via a facile and cost-effective method, and then, the in vitro and in vivo blood-repellent performances of the controllable superhydrophobic surface were systematically evaluated. First, a facile and cost-effective strategy was proposed to fabricate a controllable superhydrophobic surface on a medically pure titanium substrate using an ultraviolet laser process, ultrasonic acid treatment, and chemical modification. Second, the superhydrophobicity, durability, stability, and corrosion resistance of the superhydrophobic surface were confirmed with advanced testing techniques, which display a high contact angle, low adhesion to water and blood, and excellent resistant element precipitation. Third, the platelet-rich plasma and whole blood were applied to evaluate the hemocompatibility of the superhydrophobic surface by means of an in vitro experiment, and no blood cell activation or aggregation was observed on the superhydrophobic surface. Finally, hollow tubes with an inner superhydrophobic surface were implanted into the left carotid artery of rabbits for 2 weeks to verify the biocompatibility in vivo. The superhydrophobic surface could effectively eliminate blood cell adhesion and thrombosis. No obvious inflammation or inordinate proliferation was found by histological analysis. This research provides a facile and cost-effective strategy to prepare a blood-repellent surface, which may have promising applications in implanted biomedical devices.

Endothelial P2Y 2 ‐mediated vasoconstriction is inhibited in middle cerebral arteries of rabbits treated with clopidogrel

Clopidogrel is an effective P2Y12 antagonist used to prevent arterial thrombosis, however it's use is associated with adverse bleeding events. Clinical studies have demonstrated that clopidogrel users have an increased risk of both cerebral microbleeds and intracerebral hemorrhage. Recent reports from our laboratory and others suggest that the adverse bleeding events associated with clopidogrel may not be due to the inhibition of platelets alone. To elucidate the non-platelet effects of clopidogrel treatment, we used pressure myography to measure changes in vascular function. Male New Zealand white rabbits (2.0-2.7kg) were treated with vehicle or 10mg/kg clopidogrel for 3 days by oral gavage. These doses were chosen because they are clinically relevant and effective at inhibiting platelet aggregation. On the 4th day, the middle cerebral artery (MCA) was isolated and mounted in a pressure myograph. Cumulative concentrations (10-9-10-5M) of purinergic receptor agonists (MRS 2768 – P2Y2, MRS 4062 – P2Y4, MRS 2693 – P2Y6, and MRS 2905 – P2Y14) were added through the MCA lumen and the artery inner diameter was tracked. Analysis of MCAs from vehicle-treated rabbits demonstrated constriction in response to P2Y2, P2Y4, P2Y6 and P2Y14 activation. Three days of clopidogrel treatment did not affect the contraction induced by P2Y4, P2Y6, and P2Y14 activation. However, clopidogrel treatment did reduce the P2Y2 mediated contraction (vehicle: -22.486% +/- 2.107 vs. 10mg/kg clopidogrel: -14.159% +/- 3.785 percent baseline diameter change at 10-5M MRS 2768; p < 0.01). Removal of the endothelium revealed that endothelial P2Y2 receptors were responsible for the constriction observed upon receptor activation. Vasoconstriction is a key component of the hemostatic process. Attenuated vasoconstriction could result in an increase in bleeding. These results suggest clopidogrel inhibits P2Y2 receptor vasoconstriction in the MCA which provides a mechanistic explanation for the adverse cerebral bleeding associated with the drug.

Targeted Delivery of Salusin-α Into Rabbit Carotid Arterial Endothelium Using SonoVue.

ObjectivesA new method based on the adhesion of SonoVue to plasmids was assessed to achieve targeted gene delivery into the vascular endothelium.MethodspEGFP‐Salusin‐α and pcDNA3.1‐Salusin‐α plasmids were transfected into the arterial endothelium of different rabbit groups. Western blotting was performed to analyze the expression of EGFP and salusin‐α in the common carotid arteries of rabbits from different groups, and ELISA was performed to detect plasma salusin‐α levels in rabbits from each group; simultaneously, blood parameters of different groups of rabbits were measured.ResultsGreen fluorescence was observed in the right common carotid artery of rabbits transfected with pEGFP‐Salusin‐α, but not in the endothelial cells of not‐transfected control rabbits. The expression of salusin‐α in the transfected animals was higher than that in the control not‐transfected animals (P < .05). In rabbits transfected with pcDNA3.1‐Salusin‐α plasmid, salusin‐α expression was higher than in the not‐transfected control animals (P < .05). However, there was no significant difference in plasma salusin‐α levels between transfected animals and controls (P > .05). Blood parameters were also measured in both groups.ConclusionsOur data confirm the establishment of a new method using SonoVue for targeted gene delivery into the arterial endothelium. Our study outcomes propose a new method of intervention in atherosclerosis and a new tool for targeted gene delivery.

Pharmacological characterization of MT-1207, a novel multitarget antihypertensive agent.

Hypertension is a serious public health problem worldwide. MT-1207, chemically named 3-(4-(4-(1H-benzotriazole-1-yl)butyl)piperazine-1-yl) benzisothiazole hydrochloride, is a new chemical entity that has entered into clinical trial as antihypertensive agent in China. In this paper we report the pharmacological profile of MT-1207 regarding its acute, subacute, and long-term effects on hypertensive animal models, and its actions on isolated organs in vitro as well as its molecular targets. Blood pressure (BP) was measured in conscious animals; amlodipine was taken as a positive control drug. We showed that both single dose of MT-1207 (1.25-20 mg/kg, ig) in spontaneously hypertensive rats (SHR) and MT-1207 (0.25-6 mg/kg, ig) in two-kidney one-clip (2K1C) dogs dose-dependently decreased BP. MT-1207 quickly decreased BP within 5 min after administration; the hypotensive effect lasted for 8 and 12 h, respectively, in SHR and 2K1C dogs without reflex increase in heart rate. Multiple doses of MT-1207 (5 mg · kg-1 · d-1 in SHR; 2 mg · kg-1 · d-1 in 2K1C dogs, for 7 days) significantly decreased BP, slightly reduced heart rate, and both of them recovered after withdrawal. Long-term administration of MT-1207 (10 mg · kg-1 · d-1 for 4 months or more time) produced a stable BP reduction, improved baroreflex sensitivity, reduced renal and cardiovascular damage in SHR, and delayed stroke occurrence and death in stroke-prone SHR. In isolated rat aortic rings precontracted by adrenaline, KCl, noradrenaline or 5-hydroxytryptamine (5-HT), MT-1207 (10-9-10-4 M) caused concentration-dependent relaxation. In a panel of enzyme activity or radioligand binding assays of 87 molecular targets, MT-1207 potently inhibited adrenergic α1A, α1B, α1D, and 5-HT2A receptors with Ki < 1 nM. The antagonism of MT-1207 against these receptors was confirmed in isolated rabbit arteries. We conclude that MT-1207 is a novel and promising single-molecule multitarget agent for hypertension treatment to reduce hypertensive organ damage and stroke mortality.

Opposing Responses of the Calcium Channel Blocker Nicardipine to Vascular Stiffness in the Elastic and Muscular Arteries in Rabbits.

Aim: The cardio-ankle vascular index (CAVI) consists of intrinsic and functional arterial stiffness mainly regulated by vasoactive compounds. A new stiffness index of the aorta (aBeta) and iliac-femoral arteries (ifBeta) was determined by applying the CAVI theory to the whole aorta and iliac-femoral arteries. We investigated the changes in aBeta and ifBeta in response to decreased blood pressure (BP) induced by the Ca 2＋ channel blocker nicardipine to elucidate the involvement of Ca 2＋ in aBeta and ifBeta. Methods: Pressure waves at the origin of the aorta (oA), distal end of the abdominal aorta (dA), and left femoral artery (fA) as well as flow waves at the oA were simultaneously recorded before and after the infusion of nicardipine (50 µg/kg/min) for 2 min in 12 male rabbits under pentobarbital anesthesia. Beta was calculated using the following formula: Beta=2ρ / PP×ln (SBP / DBP)×PWV 2 , where ρ, SBP, DBP, and PP denote blood density and systolic, diastolic, and pulse pressures, respectively. aBeta, ifBeta, and aortic-iliac-femoral Beta (aifBeta) were calculated using aPWV, ifPWV, and aifPWV, respectively. Results: SBP, mean arterial pressure (MAP), DBP, and total peripheral vascular resistance significantly decreased during the administration of nicardipine, whereas cardiac output significantly increased. aBeta and ifBeta significantly increased and decreased, respectively, whereas aifBeta did not change despite the decrease in BP. ifBeta and aBeta positively and negatively correlated with BP, respectively, whereas aifBeta did not correlate with SBP. Conclusions: There were contradictory arterial responses to nicardipine between the elastic and muscular arteries. Unknown vasoconstriction mechanisms that are not involved in Ca 2＋ influx may function in the aorta in response to decreased BP.

Zoopery study on the treatment of intracranial aneurysms with a new blood flow guide device.

The purpose of this study was to evaluate the safety and effectiveness of arterial embolism device system produced by Taijie Weiye Technology Co., Ltd. Twenty healthy adult New Zealand white rabbits weighting from 3 to 4 kg were taken. Ligation and Elastic induction were used to build the aneurysm model of right common carotid artery in rabbits. The angiography and the arterial embolization device were implanted four weeks after the animal models were established. This device has excellent manufacturing, good controllability, and smooth pushing process. Five rabbits were randomly selected for angiography test to observe the healing of aneurysms in the first month, the third month and the sixth month after operation. Three other animal models with successful implantation were examined by arteriography in the first month, the third month and the sixth month, and the effect of implantation device on intercostal artery was recorded and analyzed. In the process of making aneurysm models, sixteen animals were successfully implanted with one device, two animals were given overlapping devices, and only two animals died in the process. The success rate of arterial embolic device system in the treatment of aneurysm was more than 80%. Among them, the two animals with 2 devices also achieved satisfactory therapeutic effect. According to this study, we found that the arterial embolization device system manufactured by Beijing Tajie Weiye Science and Technology Co., Ltd. was excellent in the immediate postoperative aneurysm occlusion rate and the long-term outcomes.

A novel rabbit thromboembolic occlusion model

BackgroundTo develop a preclinical thromboembolic occlusion model for studying revascularization strategies.MethodsClot analog with barium sulfate was injected into the distal aorta in 9 New Zealand white rabbits. The situation of...

Implantation of air-dried bacterial nanocellulose conduits in a small-caliber vascular prosthesis rabbit model

There are no small-caliber (<6 mm) vascular prostheses so far commercially available around the globe. Bacterial nanocellulose (BNC) is considered a promising material for small-caliber artificial blood vessel applications. Although BNC hydrogel-like (BNC-Gel) materials possess a 3D network structure, facilitating nutrient exchange when used as vascular prostheses, they are difficult to suture during surgery due to their softness. Furthermore, a water content greater than 99% prevents the material from convenient methods of preservation and transport. Air-drying the BNC (BNC-Dry) would solve these problems. The comparative morphology, mechanical properties, hemocompatibility, and cytocompatibility of the BNC-Gel and BNC-Dry conduits of 3 mm in diameter were recorded in the present study, the results indicating that the mechanical properties, hemocompatibility, and cytocompatibility of BNC-Dry conduits were superior to conduits of BNC-Gel. Forty-six days after replacement of the carotid artery in New Zealand white rabbits, the BNC-Dry conduits remained patent. Composite blood vessels composed of cellulose and autologous tissue were harvested for immunohistochemistry and immunofluorescence staining. Sections demonstrated that the outer walls of the conduits were wrapped with autologous tissue. Contractile smooth muscle cells (SMCs) were observed on the outer surface of the conduit, similar to that observed in natural blood vessels. BNC-Dry conduits exhibited excellent performance and possessed properties convenient for surgical applications as small-diameter blood vessels.

Truncated YY1 interacts with BASP1 through a 339KLK341 motif in YY1 and suppresses vascular smooth muscle cell growth and intimal hyperplasia after vascular injury

In-stent restenosis and late stent thrombosis are complications associated with the use of metallic and drug-coated stents. Strategies that inhibit vascular smooth muscle cell (SMC) proliferation without affecting endothelial cell (EC) growth would be helpful in reducing complications arising from percutaneous interventions. SMC hyperplasia is also a pathologic feature of graft stenosis and fistula failure. Our group previously showed that forced expression of the injury-inducible zinc finger (ZNF) transcription factor, yin yang-1 (YY1), comprising 414 residues inhibits neointima formation in carotid arteries of rabbits and rats. YY1 inhibits SMC proliferation without affecting EC growth in vitro. Identifying a shorter version of YY1 retaining cell-selective inhibition would make it more amenable for potential use as a gene therapeutic agent. We dissected YY1 into a range of shorter fragments (YY1A-D, YY1Δ) and found that the first two ZNFs in YY1 (construct YY1B, spanning 52 residues) repressed SMC proliferation. Receptor binding domain analysis predicts a three-residue (339KLK341) interaction domain. Mutation of 339KLK341 to 339AAA341 in YY1B (called YY1Bm) abrogated YY1B's ability to inhibit SMC but not EC proliferation and migration. Incubation of recombinant GST-YY1B and GST-YY1Bm with SMC lysates followed by precipitation with glutathione-agarose beads and mass spectrometric analysis identified a novel interaction between YY1B and BASP1. Overexpression of BASP1, like YY1, inhibited SMC but not EC proliferation and migration. BASP1 siRNA partially rescued SMC from growth inhibition by YY1B. In the rat carotid balloon injury model, adenoviral overexpression of YY1B, like full-length YY1, reduced neointima formation, whereas YY1Bm had no such effect. CD31+ immunostaining suggested YY1B could increase re-endothelialization in a 339KLK341-dependent manner. These studies identify a truncated form of YY1 (YY1B) that can interact with BASP1 and inhibit SMC proliferation, migration, and intimal hyperplasia after balloon injury of rat carotid arteries as effectively as full length YY1. We demonstrate the therapeutic potential of YY1B in vascular proliferative disease.

Thrombin-Loaded TA-CaCO3 Microspheres as a Budget, Adaptable, and Highly Efficient Hemostatic

Fast hemostasis, biosecurity, and adaptation of different bleeding sites are the major challenges for hemostatic materials. In this work, an easy-to-make, rapid hemostatic, tannic acid doped calcium carbonate microsphere with a low concentration of thrombin (Thr@TA-CaCO3) was developed. In an in vitro blood clotting assay, the hemostatic effect of Thr@TA-CaCO3 varied with the change of thrombin amount. Furthermore, the average hemostatic time can be reduced from 205 to 20 s as the thrombin levels are elevated. When applied in different hemorrhage models, the Thr@TA-CaCO3-treated group had a lower blood loss than the tannic acid modified CaCO3 (TA-CaCO3) groups. Especially in the rabbit artery injury model, the total bleeding amount in the Thr@TA-CaCO3-treated group was only 11.97% of that in the TA-CaCO3 groups, proving that Thr@TA-CaCO3 had an excellent hemostatic effect even in the case of rapidly flowing blood. Based on the above, Thr@TA-CaCO3 is a promising hemostatic agent and can be applied in more extensive clinical applications.

Investigation of the relationship between laterality and vertebral arteries in rabbits

Investigation of the relationship between laterality and vertebral arteries in rabbits