Neointimal Layer Research Articles

Lysyl oxidase expression in smooth muscle cells determines the level of intima calcification in hypercholesterolemia-induced atherosclerosis

IntroductionCardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve. MethodsImmunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOXCMLV). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9D374Y) combined with an atherogenic diet. ResultsLOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6 J) animals transduced with PCSK9D374Y and in the aortic root of ApoE−/− mice. In TgLOXCMLV mice, PCSK9D374Y transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX. ConclusionsOur results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.

Fabrication of small-diameter in situ tissue engineered vascular grafts with core/shell fibrous structure and a one-year evaluation via rat abdominal vessel replacement model

A high vascular patency was realized in the bulk or surface heparinized small-diameter in situ tissue-engineered vascular grafts (TEVGs) via a rabbit carotid artery replacement model in our previous studies. Those surface heparinized TEVGs could reduce the occurrence of aneurysms, but with a low level of the remodeled elastin, whereas those bulk heparinized TEVGs displayed a faster degradation and an increasing occurrence of aneurysms, but with a high level of the regenerated elastin. To combine the advantages of the bulk and surface graft heparinization to boost the remodeling of elastin and defer the occurrence of aneurysms, a coaxial electro-spinning technique was used to fabricate a kind of small-diameter core/shell fibrous structural in situ TEVGs with a faster degradable poly(lactic-co-glycolic acid) (PLGA) as a core layer and a relatively lower degradable poly(ε-caprolactone) (PCL) as a shell layer followed by the surface heparinization. The in vitro mechanical performance and enzymatic degradation tests revealed the resulting PLGA@PCL-Hep in situ TEVGs possessing not only a faster degradation rate, but also the mechanical properties comparable to those of human saphenous veins. After implanted in the rat abdominal aorta for 12 months, the good endothelialization, low inflammation, and no calcification were evidenced. Furthermore, the neointima layer of regenerated new blood vessels was basically constructed with a well-organized arrangement of elastin and collagen proteins. The results showed the great potential of these in situ TEVGs to be used as a novel type of long-term small-diameter vascular grafts.

Controlled Delivery of Rosuvastatin or Rapamycin through Electrospun Bismuth Nanoparticle-Infused Perivascular Wraps Promotes Arteriovenous Fistula Maturation.

In the context of arteriovenous fistula (AVF) failure, local delivery enables the release of higher concentrations of drugs that can suppress neointimal hyperplasia (NIH) while reducing systemic adverse effects. However, the radiolucency of polymeric delivery systems hinders long-term in vivo surveillance of safety and efficacy. We hypothesize that using a radiopaque perivascular wrap to deliver anti-NIH drugs could enhance AVF maturation. Through electrospinning, we fabricated multifunctional perivascular polycaprolactone (PCL) wraps loaded with bismuth nanoparticles (BiNPs) for enhanced radiologic visibility and drugs that can attenuate NIH─rosuvastatin (Rosu) and rapamycin (Rapa). The following groups were tested on the AVFs of a total of 24 Sprague-Dawley rats with induced chronic kidney disease: control (i.e., without wrap), PCL-Bi (i.e., wrap with BiNPs), PCL-Bi-Rosu, and PCL-Bi-Rapa. We found that BiNPs significantly improved the wraps' radiopacity without affecting biocompatibility. The drug release profiles of Rosu (hydrophilic drug) and Rapa (hydrophobic drug) differed significantly. Rosu demonstrated a burst release followed by gradual tapering over 8 weeks, while Rapa demonstrated a gradual release similar to that of the hydrophobic BiNPs. In vivo investigations revealed that both drug-loaded wraps can reduce vascular stenosis on ultrasonography and histomorphometry, as well as reduce [18F]Fluorodeoxyglucose uptake on positron emission tomography. Immunohistochemical studies revealed that PCL-Bi-Rosu primarily attenuated endothelial dysfunction and hypoxia in the neointimal layer, while PCL-Bi-Rapa modulated hypoxia, inflammation, and cellular proliferation across the whole outflow vein. In summary, the controlled delivery of drugs with different properties and mechanisms of action against NIH through a multifunctional, radiopaque perivascular wrap can improve imaging and histologic parameters of AVF maturation.

Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of Atherothrombosis.

Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.

Role of miRNAs regulation of Orai1 and store operated Ca2+ entry in vascular restenosis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agencia Estatal de Investigación Background The main cause of restenosis is attributed to the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Orai1 is one of the main molecular components of Store-Operated Calcium Entry (SOCE), playing a key role in VSMCs proliferation during neointima formation and vascular remodeling. Recent studies have demonstrated the implication of microRNAs (miRNAs) in VSMCs proliferation and migration, however, the role of these miRNAs as regulators of SOCE during vascular remodeling has not been described. Purpose This study aims to determine whether miRNAs regulate the intracellular Ca2+ handling, focusing on SOCE, during neointima formation. Methods Experiments were conducted in an animal rat model following the "Principles of laboratory animal care" and according to the Spanish law. The neointima development was assessed after balloon injury of carotid arteries and confirmed by haematoxylin and eosin staining, and αSMA staining of tissue sections up to 3 weeks after surgery. miRNAs array and RT-qPCR was used to examine the expression of miRNAs. Dual-Luciferase reporter assay was performed in A7R5 VSMCs line. Results Injured arteries showed significant increase in the expression of Orai1, as compared to non-injured arteries, indicating their possible participation in the neointima layer formation. Microarray of miRNAs analysis of the injured carotids compared to control carotids showed significant increase in the expression of miRNAs related to signalling pathways involving cell proliferation and migration, cell differentiation, or VSMCs contraction. Of these, we confirmed the significant increase of miR-18a-5p, miR-20a-5p, miR-20b-5p and miR-17-5p, which belong to widely studied miR-17-92 cluster involved in different cell proliferation. Moreover, we found that mimics of those miRNAs were able to regulate differentially the activity of the Orai1 promotor in A7R5 cell line, indicating that Orai1 can be targeted by miRNAs during in VSMCs. Conclusions In conclusion, our data confirms that Orai1 is upregulated during neointima formation associated with miRNAs dysregulation. Moreover, we found that Orai1-dependent SOCE can be finely regulated by miRNAs during restenosis.

Biofunctionalization of surfaces to minimize undesirable effects in cardiovascular assistance devices.

The reactivity of blood with non-endothelial surface is a challenge for long-term Ventricular Assist Devices development, usually made with pure titanium, which despite of being inert, low density and high mechanical resistance it does not avoid the thrombogenic responses. Here we tested a modification on the titanium surface with Laser Induced Periodic Surface Structures followed by Diamond Like Carbon (DLC) coating in different thicknesses to customize the wettability profile by changing the surface energy of the titanium. Four different surfaces were proposed: (1) Pure Titanium as Reference Material (RM), (2) Textured as Test Sample (TS), (3) Textured with DLC 0.3μm as (TSA) and (4) Textured with 2.4μm DLC as (TSB). A single implant was positioned in the abdominal aorta of Wistar rats and the effects of hemodynamic interaction were evaluated without anticoagulant drugs. After twelve weeks, the implants were extracted and subjected to qualitative analysis by Scanning Electron Microscopy under low vacuum and X-ray Energy Dispersion. The regions that remained in contact with the wall of the aorta showed encapsulation of the endothelial tissue. TSB implants, although superhydrophilic, have proven that the DLC coating inhibits the adhesion of biological material, prevents abrasive wear and delamination, as observed in the TS and TSA implants. Pseudo- neointimal layers were heterogeneously identified in higher concentration on Test Surfaces.

Epoxy- versus Glutaraldehyde-Treated Bovine Jugular Vein Conduit for Pulmonary Valve Replacement: A Comparison of Morphological Changes in a Pig Model.

Valved conduits are often required to replace pulmonary arteries (PA). A widely used Contegra device is made of bovine jugular vein (BJV), preserved with glutaraldehyde (GA) and iso-propanol. However, it has several drawbacks that may be attributed to its chemical treatment. We hypothesized that the use of an alternative preservation compound may significantly improve BJV conduit performance. This study aimed to compare the macroscopic and microscopic properties of the BJV treated with diepoxide (DE) and GA in a porcine model. Twelve DE-BJVs and four Contegra conduits were used for PA replacement in minipigs. To assess the isolated influence of GA, we included an additional control group-BJV treated with 0.625% GA (n = 4). The animals were withdrawn after 6 months of follow-up and the conduits were examined. Explanted DE-BJV had a soft elastic wall with no signs of thrombosis or calcification and good conduit integration, including myofibroblast germination, an ingrowth of soft connective tissue formations and remarkable neoangiogenesis. The inner surface of DE-BJVs was covered by a thin neointimal layer with a solid endothelium. Contegra grafts had a stiffer wall with thrombosis on the leaflets. Calcified foci, chondroid metaplasia, and hyalinosis were observed within the wall. The distal anastomotic sites had hyperplastic neointima, partially covered with the endothelium. The wall of GA-BJV was stiff and rigid with degenerative changes, a substantial amount of calcium deposits and dense fibrotic formations in adventitia. An irregular neointimal layer was presented in the anastomotic sites without endothelial cover in the GA BJV wall. These results demonstrate that DE treatment improves conduit integration and the endothelialization of the inner surface while preventing the mineralization of the BJV, which may reduce the risk of early conduit dysfunction.

A Valved Expanded Polytetrafluoroethylene Conduit can Acquire Endothelium After Implantation.

We demonstrate histopathology, neointimal proliferation, and neo-endothelialization in an explanted valved expanded polytetrafluoroethylene (ePTFE) conduit 40 months postimplantation that was void of calcification and inflammation, confirmed by CD-31 positivity on immunohistochemistry. Grossly, there was no distortion with preserved leaflets and lack of calcification. Good biocompatibility, nonreactivity, and low antigenicity, combined with neointimal and endothelial layer generation within the conduit might explain the low infection rates and minimal thrombogenicity. These findings support the use of handmade, valved ePTFE conduits as an economically viable option as a right ventricle to pulmonary artery conduit.

#3197 A NOVEL INVESTIGATION OF AVF WITH A SECOND HARMONIC GENERATION MICROSCOPY IN PATIENTS WITH END STAGE RENAL DISEASE

Abstract Background and Aims The population of patients with end-stage renal disease is rapidly growing and hemodialysis (HD) remains the most common treatment option. In clinical practice, the formation of arteriovenous fistulas (AVFs) is considered a priority in order to ensure optimal vascular access for HD patients. One of the complications in the formation of AVF is the hyperplasia of the neointimal layer of the vein, which leads to the failure of the fistula. The impact of the arrangement of collagen fibers in the veins of AVFs is little studied and opens wide opportunities for investigations. The structural tissue can be imaged with polarimetric nonlinear microscopy. Collagen fibers have a non-centrosymmetric structure, so they can be effectively imaged by second harmonic generation (SHG) microscopy [1]. The polarimetric nonlinear microscopy, exploiting the multidimentional tensor nature of light-matter interactions, is emerging as a valuable research tool in biomedical investigations and applications to digital pathology, and is only now becoming technically feasible for potential clinical translation [2,3]. This proposal represents a novel application of multimodal polarimetric nonlinear microscopy in histopathology, and biomedical imaging. The aim of this study is to determine the influence of the arrangement of collagen fibers in veins on the formation efficiency of AVFs by using the innovative method of nonlinear SHG microscopy. Method In this prospective study, we first used a novel SHG microscopy method to investigate AVFs venous intima hyperplasia. V. Cephalica segment is being obtained during arteriovenous fistula formation surgery from patients with end stage renal disease and after the removal of aneurysmatic or fibrotic AVF. Cross-sections of venous specimens are being fixed in 10% buffered formalin and stained with hematoxylin and eosin (H&E). Further, sample investigation is being performed in Laser Research Centre, Vilnius University using a home-built multiphoton laser-scanning microscope. The investigation is being performed with the permission of Lithuanian Biomedical Research Ethics Committee. Results We determined the arrangement of collagen fibers in veins before AVF formation and after the removal of aneurysmatic AVFs. It was observed that tunica intima of V. Cephalica is dominated both by endothelial cells and connective tissue made up of high-density collagen fibers. Whereas tunica adventitia consists mainly of collagen fibers. Collagen in tunica intima and adventitia are found to be highly noncentrosymmetric. Thus a strong SHG signal, resulting in high-contrast structural visualization of the V. Cephalica segment is generated. Conclusion Our initial investigations of AVF show clearly visible collagen fibers. The future work will focus on the structural changes of collagen fibers in the vein intimal hyperplasia. Further investigations need to be done to create artificial intelligence-based identification of new predictive collagen markers.

Heparin coated decellularized xenogeneic small diameter vascular conduit for vascular repair with early luminal reendothelialization.

Small diameter vascular graft is a clinical need in cardiovascular disease (CAD) and peripheral atherosclerotic diseases (PAD). Autologous graft has limitations in availability and harvesting surgery.To make luminal surface modification with heparin coating in xenogeneic small diameter vascular graft. We constructed a conduit from decellularized human saphenous vein (HSV) matrices in small diameter vascular graft (< 0.8mm diameter). Luminal surface modification was done with heparin coating for transplantation in the rat femoral artery. Biocompatibility of conduit was checked inChorioallantoicMembrane (CAM) assay and in vivo. The blood flow rate in conduit grafts was measured, and immuno-histological analysis was performed.CAM assay and in vivo biocompatibility test showed cellular recruitment in the HSV scaffold. Heparin binding was achieved on the luminal surface. After three months of transplantation surgery neo-intimal layer was formed in the graft. The graft was patent for two weeks after surgery. There were no statistically differences between blood flow rate in graft (at proximal end 0.5 ± 0.01m/s and at distal end 0.4 ± 0.01m/s (n = 6)) and native artery (0.6 ± 0.1m/second, (n = 3)). Biomarkers of endothelial cells, medial smooth musclecells, and angiogenesis were observed in the transplanted graft.Our study demonstrates that xenogeneic decellularized vascular grafts with surface modification with heparin coating could be useful for the replacement of small diameter vessels.

Ultrastructure of neointima of native and artificial elements of the blood circulatory system

To compare the neointima structure in conduits for coronary bypass grafting, bioprosthetic heart valves, tissue-engineered vascular grafts, and metal stents. The objects of the study were the fragments of the human internal thoracic artery, experimental biodegradable vascular prostheses, leaflets of xenopericardial bioprostheses of heart valves, and fragments of stented vessels. Tissue samples were fixed in formalin and post-fixed in osmium tetroxide. After dehydration and epoxy resin embedding, the samples were ground and polished. Samples were counterstained with uranyl acetate and lead citrate and visualized by means of backscattered scanning electron microscopy. Neointimal pattern in all samples was similar. Neointima was comprised of endothelial cells, smooth muscle cells, fibroblasts, and the extracellular matrix. Endothelial cells showed significant diversity both between different elements of the circulatory system and within the same tissue, having either elongated or polygonal shape. Adhesion of leukocytes testified to the endothelial cell activation. In the absence of inflammation in the superficial layer of the neointima, the arrangement of smooth muscle cells and extracellular matrix fibers was parallel to the endothelium. Clusters of foam cells were frequently detected around the neointimal layers with solid inclusions (metal stents or calcium deposits). Thickening of the neointima was accompanied by the presence of capillaries and capillary-like structures. Neointima formation is a typical response to the damage inflicted to the elements of the circulatory system. Neointima underwent a constant remodeling characterized by an altered cellular composition, macrophage invasion, neovascularization, and calcification.

Essential role of Orai1 and SARAF in vascular remodeling

Orai1 and STIM1, molecular components of store-operated calcium entry (SOCE), have been associated with vascular smooth muscle cell (VSMC) proliferation in vascular remodeling. Nevertheless, the role of SARAF (SOCE-associated regulatory factor), a regulatory protein involved in STIM1 inhibition, in vascular remodeling has not been examined. The aim of this study is to examine the role of SARAF and Orai1 in VSMC proliferation and neointima formation after balloon injury of rat carotid arteries. Experiments were conducted in an animal model of rat carotid angioplasty to characterize neointima formation. VSMC isolated from rat coronary arteries was also used to examine cell proliferation. The formation of neointima after balloon injury of rat carotid arteries was confirmed by hematoxylin and eosin staining of tissue sections up to 3 wk after surgery. Injured arteries showed significantly higher expression of SARAF, STIM1, and Orai1 compared with control tissues, corroborating the presence of these regulatory proteins in the neointima layer. Proximity ligation and coimmunoprecipitation assays revealed that SARAF interacts with Orai1 in the neointima. Furthermore, selective silencing of SARAF and Orai1 by small interfering RNA (siRNA) inhibited IGF-1-induced VSMC proliferation. Our data suggest that SARAF interacts with Orai1 to modulate SOCE and VSMC proliferation after vascular injury.

AbsorbaSeal™ 5.6.7F vascular closure device: A good laboratory practice chronic study evaluating safety and efficacy in a healthy porcine model.

Vascular closure devices (VCDs) are widely used for arteriotomy closure after percutaneous catheter-based procedures. In comparison to manual compression, VCDs have been associated with shorter time to hemostasis, shorter time to ambulation, and also decreased length of stay. Complexity of deployment, lack of immediate hemostasis, and residual deformity of the arterial wall remain as limitations of current VCDs. The aim of this study was to investigate the AbsorbaSeal™ 5.6.7F vascular closure device, a novel, completely bioabsorbable, intuitive, and easy to use VCD which uses a compressive, "sandwich"-type design comprising a low profile intravascular distal seal and gasket and an extravascular floating foot and proximal seal, in an open infrarenal aortic swine model. Eight fully heparinized swine at a good laboratory practices facility underwent AbsorbaSeal™ 5.6.7F VCD closure of three 6F arteriotomies each in the proximal, mid, and distal infrarenal aorta. Two swine underwent harvest at each of four time cohorts: 30, 60, 90, and 120days. Acute and chronic procedural safety and efficacy, as well as target site vascular remodeling over time, were the primary outcomes evaluated. Secondary outcome measures included local and systemic inflammatory responses, end-organ tissue analysis, and device-related complications through the follow-up periods. Histopathological evaluation was performed by a blinded pathologist. Standard statistical methods were used. In deployment of 24 AbsorbaSeal™ 5.6.7F VCDs, there were no device-related complications or mortalities. All deployments resulted in rapid arteriotomy seal (100% deployment success), with a mean time to hemostasis (cessation of arterial flow) of 21.5s (median: 6.5s) across a mean activated clotting time (ACT) of 356s. Twenty of the 24 implant sites (83%) attained complete hemostasis within 20s. Immediate post-implant and pre-termination angiographies at all time points were performed of all swine which demonstrated normal aortic appearance and tissue structure and normal downstream vascular beds. At 30days, each implant's intravascular distal seal and gasket were removed from the circulation and completely covered with a smooth neointimal layer. Minimal inflammation and no intimal or luminal thrombus were observed at any site at every time point. AbsorbaSeal™ 5.6.7F is a safe, effective, and secure VCD that demonstrates rapid hemostasis in a fully heparinized open aortic porcine model. Removal from circulation and complete coverage of the intravascular distal seal and gasket with neointima occurred within 30days post-implant. Natural transmural vessel healing from the arteriotomy itself with minimal inflammation was noted for each implant at every time point.

Application of a rabbit-elastase aneurysm model for preliminary histology assessment of the PPODA-QT liquid embolic.

Background: PPODA-QT is a novel liquid embolic under development for the treatment of cerebral aneurysms. We sought to test the rabbit-elastase aneurysm model to evaluate the tissue response following PPODA-QT embolization.Methods: Experimental elastase-induced aneurysms were created in fourteen New Zealand White Rabbits. Eight animals were used for aneurysm model and endovascular embolization technique development. Six PPODA-QT-treated animals were enrolled in the study. Control and aneurysm tissues were harvested at acute (n = 2), 1-month (n = 2), and 3-month (n = 2) timepoints and the tissues were prepared for histology assessment.Results: All fourteen rabbit-elastase aneurysms resulted in small and medium aneurysm heights (<10 mm dome height) with highly variable neck morphologies, small midline dome diameters, and beyond-wide dome-to-neck (d: n) ratios. Histological evaluation of four aneurysms, treated with PPODA-QT, demonstrated reorganization of aneurysm wall elastin into a smooth muscle layer, and observed as early as the 1-month survival timepoint. At the aneurysm neck, a homogenous neointimal layer (200–300 μm) formed at the PPODA-QT interface, sealing off the parent vessel from the aneurysm dome. No adverse immune response was evident at 1- and 3-month survival timepoints.Conclusion: PPODA-QT successfully embolized the treated aneurysms. Following PPODA-QT embolization, neointimal tissue growth and remodeling were noted with minimal immunological response. The experimental aneurysms created in rabbits were uniformly small with inconsistent neck morphology. Further testing of PPODA-QT will be conducted in larger aneurysm models for device delivery optimization and aneurysm healing assessment before human clinical investigation.

Early coronary healing in ST segment elevation myocardial infarction: sirolimus-eluting stents vs. drug-coated balloons after bare-metal stents. The PEBSI-2 optical coherence tomography randomized study.

Drug-coated balloons (DCBs) have theoretical advantages over drug-eluting stents (DESs) to facilitate stent healing. We studied whether, in patients undergoing primary coronary interventions (pPCIs), a strategy of DCB after bare-metal stent improves early healing as determined by optical coherence tomography (OCT) compared with new-generation DES. pPCI patients were randomized (1:1) to treatment with new-generation sirolimus-eluting stents (DES group) or DCB-strategy. Vessel healing was assessed by OCT at 90 days. Fifty-three patients were randomized (26 DES vs. 27 DCB). At 90 days, both strategies showed a low rate of uncovered struts (3.2 vs. 3.2%, P = 0.64) and a very high and similar rate of covered and apposed struts (96.6 vs. 96.1%, respectively; P = 0.58). However, DCB group had a significantly lower rate of major coronary evaginations (68 vs. 37%, P = 0.026), and more frequently developed a thin homogeneous neointimal layer (20 vs. 70.4%, P = 0.001) suggesting distinct superior healing at 3 months compared to DES. In pPCI both, sirolimus-DES and DCB-strategy, provide excellent strut coverage at 3 months. However, DCB ensures more advanced and optimal stent healing compared to sirolimus-DES. Further research is needed to determine whether, in patients undergoing pPCI, DCB offers superior long-term clinical and angiographic outcomes than new-generation DES (NCT03610347).

Hyperlipidemia does not affect development of elastase-induced abdominal aortic aneurysm in mice

Background and aimsHyperlipidemia is a suggested risk factor for abdominal aortic aneurysm (AAA). However, whether hyperlipidemia is causally involved in AAA progression remains elusive. Here, we tested the hypothesis that hyperlipidemia aggravates AAA formation in the widely used porcine pancreatic elastase (PPE) model of AAA in mice with varying levels of plasma lipids. MethodsPrior to PPE-surgery, 8-week-old male C57BL/6J mice (n = 32) received 1·1011 viral genomes of rAAV8-D377Y-mPcsk9 or control rAAV8 via the tail vein. Mice were fed either western type diet or regular chow. At baseline and during the 28 days following PPE-surgery, mice underwent weekly ultrasonic assessment of AAA progression. Experiments were repeated using Apolipoprotein E knockout (ApoE−/−) mice (n = 7) and wildtype C57BL/6J mice (n = 5). ResultsAt sacrifice, maximal intergroup plasma cholesterol and non-HDL/HDL ratio differences were >5-fold and >20-fold, respectively. AAA diameters expanded to 150% of baseline, but no intergroup differences were detected. This was verified in an independent experiment comparing 8-week-old male ApoE−/− mice with wildtype mice. Histological evaluation of experimental AAA lesions revealed accumulated lipid in neointimal and medial layers, and analysis of human AAA lesions (n = 5) obtained from open repair showed medial lipid deposition. ConclusionsIn summary, we find that lipid deposition in the aortic wall is a feature of PPE-induced AAA in mice as well as human AAA lesions. Despite, our data do not support the hypothesis that hyperlipidemia contributes to AAA progression.

A novel self-expanding primarily bioabsorbable braided flow-diverting stent for aneurysms: initial safety results

IntroductionThe advent of metal flow-diverting stents has provided neurointerventionalists with an option for treating aneurysms without requiring manipulations within the aneurysm sac. The large amount of metal in these stents,...

Everolimus-Eluting Biodegradable Abluminal Coating Stent versus Durable Conformal Coating Stent: Termination of the Inflammatory Response Associated with Neointimal Healing in a Porcine Coronary Model.

Objectives We evaluated the effect of the different carrier systems on early vascular response through histological analysis and scanning electron microscopy using a porcine model. Background Although Synergy™ and Promus PREMIER™ share an identical stent material and drug elution (everolimus), they use different drug carrier systems: biodegradable abluminal coating polymer or durable conformal coating polymer, respectively. However, data regarding the impact of the different coating systems on vessel healing are currently limited. Methods Twelve Synergy™ and Promus PREMIER™ were implanted in 12 swine. Histopathological analysis of the stented segments was performed on the 2nd and 14th days after implantation. Morphometric analysis of the inflammation and intimal fibrin content was also performed. Results On the 2nd day, neointimal thickness, percentage of neointimal area, and inflammatory and intimal fibrin content scores were not significantly different between the two groups. On the 14th day, the inflammatory and intimal fibrin content scores were significantly lower in Synergy™ versus those observed in Promus PREMIER™. In Synergy™, smooth muscle cells were found and the neointimal layers were smooth. In contrast, inflammatory cells were observed surrounding the struts of Promus PREMIER™. Conclusions These results demonstrate that termination of reactive inflammation is accelerated after abluminal coating stent versus implantation of conformal coating stent.

Can Redo Sternotomy Become as Easy as First-Time Sternal Opening?

Injury to vital vascular and cardiac structures is a redoubtable complication associated with redo sternotomy. This may be one reason why the pericardium should be closed whenever possible at least over the great vessels and the cranial part of the heart in every patient. This is of particular importance in those patients in whom a redo surgery may be expected (congenital surgery, valvular reconstruction and/or implantation of tissue valves, implantation of left ventricular device as bridging therapy). In many patients, however, a complete closure of the pericardium is not possible because of the intraoperative swelling of the heart or just because the necessary filling of the heart at the end of the procedure precludes a tension-free pericardial closure. In these cases, implantation of a pericardial or artificial membrane as pericardial replacement may be a wise decision. Independently of the presence of a membrane or not, computed tomography or magnetic resonance imaging is of great value before reopening the sternum to estimate the proximity of the posterior surface of the sternum to the most important cardiovascular structures (right ventricle, ascending aorta, innominate vein) or previous implants (pulmonary conduit or homograft, and saphenous vein grafts or internal thoracic artery in case of previous coronary artery bypass grafting). Previous subcutaneous implantation of different pericardial replacement patches in a porcine model has shown the following results: CorMatrix (CorMatrix Cardiovascular, Inc, Sunnyvale, CA) showed gradual and consistent patch resorption and subsiding inflammatory and fibrosis process. Full scaffold degradation and replacement by mild fibrosis and subcutaneous tissue were seen by 1 year. Xenopericardial patches remained intact, and the initially severe inflammatory and fibrotic reactions reduced gradually to moderate fibrosis and chronic inflammation. Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ) showed foreign body reaction.1Mosala Nezhad Z. Poncelet A. Fervaille C. Gianello P. Comparing the host reaction to CorMatrix and different patch materials implanted subcutaneously in growing pigs.Thorac Cardiovasc Surg. 2019; 67: 44-49Crossref PubMed Scopus (6) Google Scholar The GoreTex polytetrafluoroethylene membrane has most probably been the most frequently implanted pericardial substitute so far. Its protective effects in case of redo sternotomy are recognized, but the adhesions with the epicardial surfaces may be strong. Among more recent alternatives, CorMatrix has been described as an interesting recellularized scaffold but the results among different studies were somewhat conflicting,2Bustamante-Munguira J. Serrano R. Figuerola-Tekerina A. et al.Is CorMatrix really a recellularization scaffold as a pericardial substitute in cardiac surgery?.J Cardiovasc Surg (Torino). 2018; 59: 142-143PubMed Google Scholar whereas bovine pericardium subjected to a novel anticalcification tissue-engineering process (CardioCel, LeMaitre Vascular, Inc, Burlington, MA) seems promising: A neointimal layer of varying thickness developed on the visceral surface of 5 CardioCel explants with endothelialization of the longest duration explant.3Prabhu S. Armes J.E. Bell D. et al.Histologic evaluation of explanted tisue-engineered bovine pericardium (CardioCel).Semin Thorac Cardiovasc Surg. 2017; 29: 356-363Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar In this issue of The Annals of Thoracic Surgery, Hu and coauthors4Hu C. Tang F. Wu Q. et al.Novel trilaminar polymeric anti-adhesion membrane prevents postoperative pericardial adhesion.Ann Thorac Surg. 2021; 111: 184-190Abstract Full Text Full Text PDF Scopus (8) Google Scholar from Beijing have to be congratulated for another important step—that is, a novel trilaminar membrane that was compared (mainly adhesive effects) to the well-known expanded polytetrafluoroethylene membrane in an animal study. The goal of this new membrane is to minimize post-sternotomy adhesions (through the resorbable components) while maintaining a permanent physical barrier (through the middle layer). All layers contain a novel polymer made of polyvinyl alcohol and carboxymethylcellulose. Because the generation of adhesions and granulation tissue are most active 5 to 7 days after implantation and adhesions become stable approximately from day 14 post implantation, the new material resorbs rapidly after implantation during initial surgery. This might be of particular interest if, for any reason, a reexploration becomes necessary during the early follow-up period. Looking at the microscopic specimen in animals, every cardiac surgeon may be eager to have this new pericardial replacement membrane in their fingers as soon as available on the market. Novel Trilaminar Polymeric Antiadhesion Membrane Prevents Postoperative Pericardial AdhesionThe Annals of Thoracic SurgeryVol. 111Issue 1PreviewPostoperative pericardial adhesion formation is a prominent cause of morbidity and death in cardiovascular surgery, but there is still no ideal prevention method, especially in redo cases. This study investigated a novel antiadhesion trilaminar polymeric film compared with the Gore PRECLUDE Pericardial Membrane (W. L. Gore & Associates, Flagstaff, AZ) and a negative control. Full-Text PDF

Electrospun polyurethane-based vascular grafts: physicochemical properties and functioning in vivo

General physicochemical properties of the vascular grafts (VGs) produced from the solutions of Tecoflex (Tec) with gelatin (GL) and bivalirudin (BV) by electrospinning are studied. The electrospun VGs of Tec-GL-BV and expanded polytetrafluoroethylene (e-PTFE) implanted in the abdominal aorta of 36 Wistar rats have been observed over different time intervals up to 24 weeks. A comparison shows that 94.5% of the Tec-GL-BV VGs and only 66.6% of e-PTFE VGs (р = 0.0438) are free of occlusions after a 6 month implantation. At the intermediate observation points, Tec-GL-BV VGs demonstrate severe neovascularization of the VG neoadventitial layer as compared with e-PTFE grafts. A histological examination demonstrates a small thickness of the neointima layer and a low level of calcification in Tec-GL-BV VGs as compared with the control grafts. Thus, polyurethane-based protein-enriched VGs have certain advantages over e-PTFE VGs, suggesting their utility in clinical studies.