The combination of a natural polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a synthetic hydrophobic polymer poly(ε-caprolactone) (PCL) is promising for the preparation of biodegradable and biocompatible small-diameter vascular grafts for bypass surgery. However, physico-mechanical properties and endothelialization rate of PHBV/PCL grafts are poor. We suggested that incorporation of vascular endothelial growth factor (VEGF) into PHBV/PCL grafts may improve their physico-mechanical properties and enhance endothelialization. Here we compared morphology, physico-mechanical properties, and in vivo performance of electrospun small-diameter vascular grafts prepared from PHBV/PCL with and without VEGF. Structure of the graft surface and physico-mechanical properties were examined by scanning electron microscopy and universal testing machine, respectively. Grafts were implanted into rat abdominal aorta for 1, 3, and 6 months with the further histological, immunohistochemical, and immunofluorescence examination. PHBV/PCL grafts with and without VEGF were highly porous and consisted mostly of nanoscale and microscale fibers, respectively. Mean pore diameter and mean pore area were significantly lower in PHBV/PCL/VEGF compared to PHBV/PCL grafts (1.47 μm and 10.05 μm2; 2.63 μm and 47.13 μm2, respectively). Durability, elasticity, and stiffness of PHBV/PCL grafts with VEGF were more similar to internal mammary artery compared to those without, particularly 6 months postimplantation. Both qualitative examination and quantitative image analysis showed that three-fourths of PHBV/PCL grafts with VEGF were patent and had many CD31-, CD34-, and vWF-positive cells at their inner surface. However, all PHBV/PCL grafts without VEGF were occluded and had no or a few CD31-positive cells at the inner surface. Therefore, VEGF enhanced endothelialization and improved graft patency at all the time points in a rat abdominal aorta replacement model. In conclusion, PHBV/PCL grafts with VEGF have better biocompatibility and physico-mechanical properties compared to those without. Incorporation of VEGF improves graft patency and accelerates formation of endothelial cell monolayer.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine–glycine–aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31+/CD34+/vWF+ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31+CD34−vWF+ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31+/CD34+ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.

The development of novel biodegradable vascular grafts of a small diameter (<6 mm) is an unmet clinical need for patients requiring arterial replacement. Here we performed a pre-clinical study of new small-caliber biodegradable vascular grafts using a sheep model of carotid artery implantation. The 4 mm diameter vascular grafts were manufactured using a mix of polyhydroxybutyrate/valerate and polycaprolactone supplemented with growth factors VEGF, bFGF and SDF-1α (PHBV/PCL-GFmix) and additionally modified by a polymer hydrogel coating with incorporation of drugs heparin and iloprost (PHBV/PCL-GFmixHep/Ilo). Animals with carotid artery autograft implantation and those implanted with clinically used GORE-TEX® grafts were used as control groups. We observed that 24 h following surgery, animals with carotid artery autograft implantation showed 87.5% patency, while all the PHBV/PCL-GFmix and GORE-TEX® grafts displayed thrombosis. PHBV/PCL-GFmixHep/Ilo grafts demonstrated 62.5% patency 24 h following surgery and it had remained at 50% 1 year post-operation. All the PHBV/PCL grafts completely degraded less than 1 year following surgery and were replaced by de novo vasculature without evidence of calcification. On the other hand, GORE-TEX® grafts displayed substantial amounts of calcium deposits throughout graft tissues. Thus, here we report a potential clinical usefulness of PHBV/PCL grafts upon their additional modification by growth factors and drugs to promote endothelialization and reduce thrombogenicity.

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A case of successful emergency carotid endarterectomy (CEE) in the acute period of ischemic stroke (within an hour after the onset of symptoms) in a patient with acute occlusive thrombosis of the internal carotid artery in the course of moderate-severe COVID-19 with a positive result of the polymerase chain reaction of the nasopharyngeal smear for SARS-CoV-2. The diameter of the ischemic focus in the brain according to multispiral computed tomography did not exceed 2.5 cm. The course of ischemic stroke was characterized by mild neurological deficit (score 5 according to National Institute of Health Stroke Scale). It was demonstrated that the severity of the patient’s condition was associated with bilateral, polysegmental, viral penvmonia with 65% damage to the lung tissue, a decrease in SpO2 to 93%. Laboratory noted coagulopathy with an increase in D-dimer (2837.0 ng/ml), prothrombin according to Quick (155.3%), fibrinogen (14.5 g/l) and signs of a “cytokine storm” with leukocytosis (28.4 10E9/l), an increase in C-reactive protein (183.5 mg/l), ferritin (632.8 ng/ml), interleukin-6 (176.9 pg/ml). The patient underwent glomus-sparing eversional CEE. The intervention was performed under local anesthesia due to the high risk of developing pulmonary barotrauma when using mechanical ventilation. To prevent the development of acute hematoma, a double active drainage was used into the paravasal space and subcutaneous fatty tissue (SFT). In case of thrombosis of one of the drainages, the second could serve as a spare. Also, upon receipt of hemorrhagic discharge from the drainage located in the SFT, the patient would not need to be transported to the operating room. Removal of skin sutures with revision and stitching of the bleeding source could be performed under local anesthesia in a dressing room. The postoperative period was uneventful, with complete regression of neurological symptoms. Used anticoagulant (heparin 5 thousand units 4 times a day s/c) and antiplatelet therapy (acetylsalicylic acid 125 mg at lunch). The patient was discharged from the hospital on the 12th day after CEE in satisfactory condition.

Aim of study. Analysis of the results of a new method of emergency glomus-sparing carotid endarterectomy (CEE) according to A.N. Kazantsev in the acute period of ischemic stroke.Material and methods. This cohort comparative prospective open-label study from January 2017 to April 2020 included 517 patients operated on for occlusive stenotic lesions of the internal carotid arteries (ICA) in the acute period of ischemic stroke (within 24 hours after the development of ischemic stroke). Depending on the implemented revascularization strategy, all patients were divided into three groups: group 1 — 214 patients (41.4%) — glomus-sparing CEE according to A.N. Kazantsev; 2nd group — 145 (28%) — classical CEE with plasty of the reconstruction zone with a patch; 3rd group — 158 (30.6%) — eversion CEE. The observation period was 35.2±9.6 months. Glomus-saving СE according to A.N. Kazantsev was carried out as follows. Arteriotomy with transition to the common carotid artery (CCA) was performed along the inner edge of the external carotid artery (ECA) adjacent to the carotid sinus, 2–3 cm above the ostium, depending on the spread of atherosclerotic plaque, the ICA was cut off at the site formed by the sections of the wall of the ECA and CCA. Then endarterectomy from the ICA was performed using the eversion technique. The next step was open endarterectomy from ECA and CCA. Then the ICA was implanted in the same position on the saved site.Results. In the hospital follow-up period, there were no significant intergroup differences in the number of complications. However, it should be noted that in the CEE group according to A.N. Kazantsev had no adverse cardiovascular events. In the long-term follow-up period, the smallest number of cardiovascular accidents was detected after CEE according to A.N. Kazantsev. However, intergroup differences were found only in the combined endpoint and the incidence of thrombosis, which were the highest in the 2nd and 3rd groups (p = 0.01). When analyzing the survival curves, it was revealed that the greatest number of cardiovascular accidents in the group of classical and eversion CEE occurred either during the hospital observation period or during the first months after surgery, and after CEE according to A.N. Kazantsev - in a year or more. When analyzing the graph of the dynamics of systolic blood pressure (BP), it was revealed that after glomus-sparing CEE according to A.N. Kazantsev, stable numbers are maintained while receiving preoperative antihypertensive therapy and do not rise above 140 mm Hg. In turn, after classical and eversion CEE, critical hypertension persists in the first three days, which is difficult to treat. In the future, blood pressure figures are unstable and fluctuate in the range from 140 to 160 mm Hg. All cases of myocardial infarction and ischemic stroke were recorded against the background of critical numbers of systolic blood pressure, reaching 180-200 mm Hg.Conclusion. The presented glomus-sparing carotid endarterectomy according to A.N. Kazantsev meets the modern standards of carotid surgery, combined with the minimum permissible risks of developing adverse cardiovascular events, both in hospital and in the long-term follow-up. The confident effect of the developed revascularization is based on the precise removal of plaque from the common, external and internal carotid arteries, as well as maintaining the stability of hemodynamic parameters.