Neointimal Thickness Research Articles

Multimodality intravascular imaging of bioresorbable vascular scaffolds implanted in vein grafts.

IntroductionThere are no data presenting a serial assessment of vein graft healing after bioresorbable vascular scaffold (BVS) implantation at long-term follow-up.AimTo describe ABSORB BVS healing in vein grafts by optical coherence tomography (OCT) and high-definition intravascular imaging (HD-IVUS) at long-term follow-up.Material and methods: The study group consisted of 6 patients. The first patient had serial OCT assessment of BVS implanted in the saphenous vein grafts (SVG) at baseline and at 3-, 6-, 18-month follow-up and the second patient had OCT assessment of BVS implanted in the SVG at baseline and 24-, 48-month follow-up. The second and the third patients had OCT and HD-IVUS imaging at baseline and 48-month follow-up. The last 3 patients had OCT imaging of BVS implanted in the native coronary artery at 48-month follow-up.ResultsThere were no differences in neointimal hyperplasia after BVS implantation between each time point. However, complete scaffold coverage was observed only 48 months after implantation. Out of 202 analyzed scaffold struts, there were 67 (33%) black boxes detectable at 48-month follow-up. HD-IVUS presented plaque burden up to 67% at the segment of BVS implantation at 48-months follow-up. There was a difference in neointimal hyperplasia thickness (1.27 (0.953–1.696) vs. 0.757 (0.633–0.848), p < 0.001) between a native coronary artery and BVS scaffolds at 48-month follow-up.ConclusionsBioresorbable vascular scaffold implanted in SVG characterized moderate neointimal hyperplasia as excessive as compared to native coronary arteries at long-term follow-up. The complete scaffold coverage was observed only 48 months after implantation.

Atherosclerotic Component of the Yellow Segment After Drug-Eluting Stent Implantation on Coronary Angioscopy - An Ex-Vivo Validation Study.

Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut. In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

Optical coherence tomography substudy of a prospective multicentre randomised post-market trial to assess the safety and effectiveness of the Firehawk cobalt-chromium coronary stent (rapamycin target-eluting) system for the treatment of atherosclerotic lesions: TARGET All Comers.

Durable polymer drug-eluting stents (DP-DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this optical coherence tomography (OCT) substudy was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (Firehawk®) (BP-DES) versus the DP-DES (XIENCE) at 90 days in an all-comers patient population. The TARGET All Comers study is a prospective multicentre randomised post-market trial of 1,656 patients randomised 1:1 to Firehawk or XIENCE at 21 centres in 10 European countries. The TARGET OCT substudy enrolled 36 consecutive patients with 52 lesions at six centres proficient in OCT. Follow-up OCT was performed at three months or prior to revascularisation when occurring before the three-month window. The substudy was designed for non-inferiority of the primary endpoint of neointimal thickness. At follow-up, the mean neointimal thickness by OCT (52 lesions: Firehawk, n=24; XIENCE, n=28), was not significantly different between groups (Firehawk 75.5 μm vs. XIENCE V 82.3 μm) meeting the primary endpoint of non-inferiority (pnoninferiority<0.001). The percentage of stent strut coverage was high in both groups (strut level: 99.9±0.3% vs. 100±0.1%, p=0.26), and the proportion of malapposed struts (1.0±1.6% vs. 1.2±2.0%, p=0.51) was low in both groups. Based on OCT, the Firehawk BP-DES has a similar healing response three months after implantation compared to the DP-DES, with near complete strut coverage, moderate neointima formation and minimal strut malapposition.

Haem oxygenase-1 inhibits neointimal hyperplasia in rat by histone deacetylase 2

It has been reported that haem oxygenase-1 (Hmox1) induction attenuates neointimal thickening. Here we further investigated the potential mechanisms regulating this important pathological process. We revealed that histone deacetylase 2 (HDAC2) was induced following Hmox1 induction under 1% oxygen treatment and this induction was attenuated after the treatment of siRNA against Hmox1. Interestingly, this HDAC2 induction was dependent on Hmox1 protein as well as its enzymatic activity, and was regulated by carbon monoxide released from haem degradation. Furthermore, histone deacetylase inhibitor, trichostatin A, successfully abrogated the inhibitory effects of vascular smooth muscle migration and proliferation by Hmox1 induction in vitro. In a rat carotid balloon injury model, similar results were observed by measuring neointimal thickening. As such, we concluded that Hmox1 inhibits neointimal hyperplasia via HDAC2 in rats.

Decellularized Carotid Artery Functions as an Arteriovenous Graft

BackgroundProsthetic arteriovenous grafts (AVG) continue to have a high rate of failure in clinical use, yet there is continued clinical demand for them. However, there is no small animal model of AVG to test novel tissue-engineered vascular grafts. We established a new rat arteriovenous graft model to compare the healing of decellularized carotid artery (CA) to autologous CA. Materials and methodsThe infrarenal vena cava and aorta of Wistar rats were exposed and dissected free below renal artery. A longitudinal 1 mm venotomy and arteriotomy were made on the anterior walls. The conduit was either autologous CA or heterologous decellularized CA; a conduit was sewn to the inferior vena cava and aorta in end-to-side fashion. Rats were sacrificed on postoperative day 21 for examination. ResultsAll rats survived without heart failure. Conduits had 100% patency rate (day 21) in both the control and decellularized CA groups (n = 6). Both control and decellularized CA showed similar rates of reendothelialization, inflammatory cell infiltration, and cell turnover. The outflow vein beyond the autologous or decellularized conduits showed similar neointimal thickness and cell turnover. ConclusionsDecellularized CA may be a viable tissue engineering graft for use as an arteriovenous graft for dialysis access. The rat aorta-vena cava graft is a useful model to test new materials including tissue-engineered grafts for use as AVG.

Correlation between pre-procedural plaque morphology and patterns of in-stent neointimal hyperplasia at 1-year follow-up in patients treated with new-generation drug-eluting stents: An optical coherence tomography based analysis.

Several factors affect the in-stent intimal healing process after drug-eluting stents (DESs) implantation. We hope to investigate the influence of plaque characteristics on subsequent heterogeneous neointimal hyperplasia (NIH) using optical coherence tomography (OCT). The study population consisted 217 patients with single-vessel de novo lesions who underwent both pre-procedural OCT scan and 12-month follow-up OCT examination. NIH is defined as at least five consecutive cross-sectional images with no less than 100µm neointimal thickness. According to OCT follow-up, patients were divided into three groups: neointima-covered group, homogeneous, and heterogeneous NIH group. 102 patients were categorized in neointima-covered group, 91 and 24 patients in homogeneous and heterogeneous group, respectively. Time interval between OCT scans was similar (P = 0.55). No significant differences in the patients' age, gender, comorbidities, laboratory findings, procedural, and lesion-related findings were found among these three groups. Heterogeneous group tended to have more subjects presented as acute coronary syndrome (ACS) (P = 0.04) and mean macrophage grade was higher in this group (P = 0.01). While no statistically significant difference concerning mean intimal thickness (P = 0.21) or neointimal burden (P = 0.73) was found between homogeneous and heterogeneous group. Multivariate logistic regression analysis showed that mean macrophage grade (OR: 2.26, 95%CI: 1.12 to 4.53, P = 0.02) and initial clinical presentation of ACS (OR: 2.81, 95%CI: 1.03 to 7.72, P = 0.04) were significant independent risk factors for heterogeneous NIH. Mean macrophage grade measured by OCT as a semi-quantitative morphological risk factor, as well as clinical presentation of ACS, was associated with in-stent neointimal heterogeneity after DES implantation.

A Patient-Specific Study Investigating the Relation between Coronary Hemodynamics and Neo-Intimal Thickening after Bifurcation Stenting with a Polymeric Bioresorbable Scaffold

We present an application of a validated reconstruction methodology for the comparison between patient-specific hemodynamics and neo-intimal thickening at nine months from the intervention. (1) Background: Coronary bifurcation stenting alters the vessel geometry, influencing the local hemodynamics. The evaluation of wall shear stress (WSS) relies on the application of computational fluid dynamics to model its distribution along the coronary tree. The endothelium actively responds to WSS, which triggers eventual cell proliferation to cover the stent struts. (2) Methods: Baseline optical coherence tomography and angiographic data were combined to reconstruct a patient-specific coronary bifurcation with an implanted bioresorbable scaffold and to simulate the hemodynamics. Results were linked with the neo-intimal thickening after nine months from the intervention. (3) Results: Blood velocity patterns were disrupted at the bifurcation due to the presence of the stent. It was observed that 55.6% of the scaffolded lumen surface was exposed to values of time-averaged WSS lower than 0.4 Pa. Follow-up images showed a luminal narrowing of 19% in the main branch. There was also a complete coverage in 99% of struts. (4) Conclusions: This approach provided valuable complementary information that might improve the clinical outcomes in this subset of coronary diseases.

TCT-158 Post-implantation Strut Protrusion and Neointimal Thickness at follow-up in Absorn Bioresorbable Scaffold: A serial Shear Stress Analysis Up to Five Years

To evaluate effect of strut protrusion(SP) on wall shear stress(WSS) and neointimal growth(NG) 1- and 5-year after implantation of Absorb scaffold. 8 patients were selected from first-in-man study. Following 3D reconstruction of coronaries,WSS was quantified using Newtonian steady flow simulation

A serial 3- and 9-year optical coherence tomography assessment of vascular healing response to sirolimus- and paclitaxel-eluting stents

Early-generation drug-eluting stents (DES) have been demonstrated to delay vascular healing. Limited optical coherence tomography (OCT) data on the very long-term neointimal response after DES implantation are available. The aim of this study was a serial OCT assessment of neointimal thickness, stent strut coverage, malapposition, and protrusion as markers of neointimal response at 3 and 9 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). In this single-centre, longitudinal study consecutive patients undergoing elective PCI with SES or PES were included. OCT analysis was performed after 3 and 9 years by the independent core laboratory. A total of 22 subjects (8 SES and 14 PES) underwent an OCT assessment at 3 and 9 years post index procedure. The lumen, neointimal and malapposition area and the neointimal thickness (SES ∆50 µm, p = 0.195, PES ∆10 µm, p = 0.951) did not change significantly over the 6 year follow-up. No differences in the incidence of uncovered, malapposed or protruding struts were found in each type of stent. At 3 and 9 years after PCI, implantation of early-generation SES and PES may be associated with similar neointimal thickness, strut coverage, malapposition and protrusion, as assessed by serial OCT examination among patients with uneventful follow-up at 3 years post procedure. The small size of the study warrants judicious interpretation of our results and confirmation in larger multimodality imaging studies, including patients treated with contemporary stent platforms.

Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model

ObjectiveInflammation is a key driver of excessive neointimal hyperplasia within vein grafts. Recent work demonstrates that specialized proresolving lipid mediators biosynthesized from omega-3 polyunsaturated fatty acids, such as resolvin D1 (RvD1), actively orchestrate the process of inflammation resolution. We investigated the effects of local perivascular delivery of RvD1 in a rabbit vein graft model. MethodsIpsilateral jugular veins were implanted as carotid interposition grafts through an anastomotic cuff technique in New Zealand white rabbits (3-4 kg; N = 80). RvD1 (1 μg) was delivered to the vein bypass grafts in a perivascular fashion, using either 25% Pluronic F127 gel (Sigma-Aldrich, St. Louis, Mo) or a thin bilayered poly(lactic-co-glycolic acid) (PLGA) film. No treatment (bypass only) and vehicle-loaded Pluronic gels or PLGA films served as controls. Delivery of RvD1 to venous tissue was evaluated 3 days later by liquid chromatography-tandem mass spectrometry. Total leukocyte infiltration, macrophage infiltration, and cell proliferation were evaluated by immunohistochemistry. Elastin and trichrome staining was performed on grafts harvested at 28 days after bypass to evaluate neointimal hyperplasia and vein graft remodeling. ResultsPerivascular treatments did not influence rates of graft thrombosis (23%), major wound complications (4%), or death (3%). Leukocyte (CD45) and macrophage (RAM11) infiltration was significantly reduced in the RvD1 treatment groups vs controls at 3 days (60%-72% reduction; P < .01). Cellular proliferation (Ki67 index) was also significantly lower in RvD1-treated vs control grafts at 3 days (40%-50% reduction; P < .01). Treatment of vein grafts with RvD1-loaded gels reduced neointimal thickness at 28 days by 61% vs bypass only (P < .001) and by 63% vs vehicle gel (P < .001). RvD1-loaded PLGA films reduced neointimal formation at 28 days by 50% vs bypass only (P < .001). RvD1 treatment was also associated with reduced collagen deposition in vein grafts at 28 days. ConclusionsLocal perivascular delivery of RvD1 attenuates vein graft hyperplasia without associated toxicity in a rabbit carotid bypass model. This effect appears to be mediated by both reduced leukocyte recruitment and decreased cell proliferation within the graft. Perivascular PLGA films may also impart protection through biomechanical scaffolding in this venous arterialization model. Our studies provide further support for the potential therapeutic role of specialized proresolving lipid mediators such as D-series resolvins in modulating vascular injury and repair.

Sheep models for evaluation of novel patch and prosthesis material in vascular surgery: tips and tricks to avoid possible pitfalls

BackgroundIn vascular surgery, novel synthetic prosthesis materials for patch-angioplasties, interpositions, bypasses and shunts are continuously under development and optimization. The characteristics of an ideal vascular prosthesis would display long-term patency, biocompatibility, durability, low porosity, lack of stich hole bleeding, ease of handling, kink resistance, infection resistance and reasonable costs. The aim of this study was to establish and report a reliable sheep model including potential pitfalls where those parameters could be analyzed. Before surgery, sheep were acclimatized for 4–8 weeks, during which parasite infections were treated and blood and serum parameters monitored. Twenty-four sheep underwent surgery, and carotid patch-angioplasties (n = 12), graft interpositions (n = 6) or arteriovenous prosthetic shunts (n = 6) were implanted. Half of the animals in each group were sacrificed after 2 weeks and the other half after 8 weeks. The implants were analyzed for patency, endothelialization, thrombogenicity and biocompatibility by clinical observation, blood flow measurement and pathological and histopathological (H&E, EvG) as well as immunohistochemical (Ki67, CD31) evaluations.ResultsHealth monitoring of the sheep revealed a parasitic burden with endoparasites in all animals. Some animals showed thereby infestations in the bile duct causing fibrotic cholangitis with calcifications in the liver. In addition, sarcosporidia were detected in histopathological specimen of the heart in all animals. Parasitic burden correlated with blood counts and serum bilirubin levels. Both were significantly reduced by albendazole treatment within the acclimatization time. Patches, interposition grafts, and straight shunts were successfully implanted bilaterally in all animals. The total average operation time was 136 ± 21 min. Most animals (23/24) showed good patency rates and general condition after implantation. Pathological and histopathological/immunohistochemical analyses were suitable to determine thrombogenicity, endothelialization, cellular/fibroblastic proliferation, biocompatibility, inflammatory cell infiltration, and thickness of neointima in the prosthesis material.ConclusionsWe have developed a suitable experimental protocol with standardized and successful anesthesia- and surgical-procedures for patch-angioplasty, graft interposition, and arteriovenous prosthetic shunts. This sheep model allows testing of new prosthetic materials for biocompatibility, thrombogenicity, and endothelialization.

Favorable early vessel healing after everolimus-eluting stent implantation: 3-, 6-, and 12-month follow-up of optical coherence tomography

BackgroundAlthough a prospective randomized control study revealed that 3-month dual anti-platelet therapy (DAPT) is safe and does not compromise the efficacy of everolimus-eluting stent (EES) in selected patients, detailed vessel healing at early phase after EES implantation has yet to be investigated in Japanese patients. Methods and resultsA total of 27 lesions in 19 patients treated with EES were serially evaluated by using optical coherence tomography (OCT) at 3, 6, and 12 months after stent implantation. In addition to standard quantitative OCT parameters, the percentage of stents with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated.There was a significant, but small increase in neointimal thickness (63±17μm; 83±30μm; and 111±44μm, respectively; p=0.006) and small decrease in average lumen area (6.80±2.57mm2, 6.62±2.58mm2, 6.33±2.58mm2, p=0.038) from the 3- to the 12-month follow-up. The incidences of uncovered and malapposed struts were low at 3 months and did not significantly change at 6 months and 12 months (3.01±4.43; 2.45±3.75; and 1.47±3.16, p=0.143, and 0.75±0.65; 0.63±0.73; and 0.58±1.42, p=0.162, respectively). Also, frequency of struts with PLIA was already low at three months and significantly decreased during the follow-up (6.4±6.5; 4.6±5.4; and 2.3±3.3, respectively; p=0.001). ConclusionFavorable vessel healing was achieved at 3 months after EES implantation without neointimal hyperplasia which was persistently suppressed up to 12 months.

Actions of Liraglutide on Vascular Endothelial Cells Play a Central Role in the Suppression of Atherosclerosis in Diabetic Mice

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to exert direct anti-atherosclerotic effects through multiple actions on various cells. However, it is unclear which action is crucial. We investigated the role of the anti-atherogenic effects of liraglutide (Lira) on vascular endothelial cells (VECs) in vivo. Methods: Streptozotocin-induced diabetic apolipoprotein E-null mice (male, 20 weeks) were randomly assigned to treatment with saline or Lira (17 nmol/kg/d) and underwent femoral artery (FA) wire injury to remove VECs. Thioglycolate-exudated peritoneal macrophages and vascular samples (aorta, FA, and right brachiocephalic artery [RBCA]) were collected 4 weeks after treatment. Results: In the Lira group, active GLP-1 levels were significantly higher (4.7 ± 1.1 vs. 2.8 ± 0.3 pmol/L) and levels of HbA1c (8.9 ± 0.4% vs. 8.3 ± 0.5%) and total cholesterol (492 ± 8 vs. 457 ± 19 mg/dL) were significantly lower than in controls. Lira significantly reduced the atherosclerotic plaque (oil red O [ORO]-stained area) on the surface of the whole aorta by 36% and the plaque volume and intraplaque macrophage infiltration in the aortic root by 56% and 55%, respectively. Additionally, Lira suppressed the expression of inflammatory cytokines in macrophages by 40-45% (p &amp;lt; 0.05) and the expression of inflammatory cytokines in the RBCAs, which are prone to lesion, plaque formation, and rupture. In FA, no plaque was observed in uninjured lesions, while severe plaque formation occurred in injured lesions. In contrast, Lira failed to suppress plaque volume or neointimal thickening in FAs where the VECs were removed (ORO-stained area/vascular wall area: 0.51 ± 0.vs. 0.55 ± 0.08, neointimal area/medial area: 2.4 ± 1.2 vs. 2.6 ± 0.7), indicating that Lira cannot suppress atherosclerosis independent of VECs. Conclusions: Of the multiple actions on various cells, VECs play a central role in the suppression of atherosclerosis mediated by Lira. Disclosure M. Hiromura: None. Y. Mori: None. M. Koshibu: None. H. Kushima: None. K. Kohashi: None. M. Terasaki: None. T. Hirano: Speaker's Bureau; Self; Novo Nordisk Inc., AstraZeneca.

Gene therapy with antisense oligonucleotides silencing c-myc reduces neointima formation and vessel wall thickness in a mouse model of vein graft disease

Gene therapy for avoiding intimal hyperplasia of vein grafts after coronary artery bypass grafting is still discussed controversially. A promising application of gene therapy in vein grafts is the use of antisense oligonucleotides to block the expression of genes encoding cell cycle regulatory proteins in vascular smooth muscle cells. C-myc, either directly or by regulating the expression of other proteins, controls cell proliferation, apoptosis and cell survival, tissue remodeling, angiogenesis, cell metabolism, production of inflammatory and anti-inflammatory cytokines, and also participates in cell transformation.Forty C57BL/6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a previously described cuff technique. Twenty mice received periadventitial administration of antisense oligonucleotides directed against c-myc (treatment group), the other twenty mice received no treatment (control group). All vein grafts were harvested two weeks after surgery, dehydrated, wax embedded, cut into slides of 2 μm thickness, stained and histologically and immunohistochemically examined under light microscope.In our study, we could show the promising effects of antisense oligonucleotide treatment in a mouse model of vein graft disease including the significant reduction of neointimal, media and total vessel wall thickness with a significantly lower percentage of SMA positive cells, elastic fibres and acid mucopolysaccharides in the neointima and media, a decreased vascularization, and a lower expression of PDGFR ß, MMP-9 and VEGF-A positive cells throughout the whole vein graft wall.

Pathological mechanisms of left main stent failure

BackgroundDespite the increasing use of left main (LM) percutaneous coronary intervention (LM-PCI), there have been no pathological studies devoted to understanding the causes of LM stent failure. We aimed to systematically determine the pathological mechanisms of LM stent failure. Methods and resultsFrom the CVPath Stent registry, a total of 46 lesions were identified to have LM-PCI. Pathologic stent failure (PSF) was defined as stent thrombosis, restenosis and in-stent chronic total occlusion (CTO). Failed and patent LM stented lesions were pathologically assessed to determine predictors of PSF. Malapposition and uncovered struts were numerically greater in the LM ostium, body, and bifurcation while neointimal thickness was relatively greater in bifurcation and proximal circumflex. In this study cohort, half of the lesions (n = 23) showed PSF. Stent thrombosis (ST, n = 18) was the major mode of PSF followed by in-stent CTO (n = 4) and restenosis (n = 1). Failed lesions showed significantly greater prevalence of malapposition >20% of struts/section (65% vs. 13%, P < 0.01), stent struts crossing an ostial side branch >30% of the circumference (48% vs. 13%, P < 0.01) and uncovered struts >30% (57% vs. 18%, P = 0.03). In multivariate analysis, the prevalence of malapposition >20% was the strongest risk factor for PSF (Odds ratio 8.0, 95% confidence interval 1.8–45.4, P < 0.01) followed by struts crossing an ostial side branch >30% (Odds ratio 4.2, 95% confidence interval 0.8–24.7, P = 0.09). ConclusionOur data demonstrate the main pathological predictors for LM stent failure are malapposition and struts crossing an ostial side branch and suggest that imaging-guided PCI may be important.

Abstract 237: The Inhibitory Effect on Vascular Smooth Muscle Cell Hyperplasia in Artificial Atherosclerotic Mouse Model via miR-155 Induced NoxA1 Down Regulation

Objective: To investigate the protective efficacy of miR-155 on down regulating NoxA1 gene expression, resulting in an inhibitory effect of vascular smooth muscle cell (VSMC) over proliferation and thus alleviating the progression of coronary artery atherosclerosis in mouse disease model. Methods: Carotid artery of C57BL6 mouse was used for VSMC primary culture. The isolated VSMC was transfected with recombinant Pad2YFG adenovirus fluorescent vector with miR-155 fragment (mimic or mutant). Fluorescence microscope was applied to observe the transfection rate of miR-155 into VSMC. Artificial artery-injured mouse model fed with high-fat diet was established as host to accept VSMC transplantation via tail vein injection for 3 consecutive days. Aortic and carotid arteries were extracted at week 6. Distribution of miR-155 was quantified; protein and RNA were extracted to detect NoxA1 and NADPH expression in vehicle control, miR-155 mimic group, and the inhibitor group. Immunohistochemistry was performed in arteries section to compare the thickness of neointima and assess the severity of AS of each group. Results: The miR-155 distribution was observed varied at week 6 in control, miR-155 mimic and inhibitor groups. The NoxA1 protein expression in VSMC was decreased in mimic group at week 6 vs control and inhibitor groups (p&lt;0.05); no significant difference of NADPH expression was observed in all groups. The NoxA1 and NADPH gene expression in VSMC were both found reduced compared with those of control group at week 6 (p&lt;0.05). Immunohistochemistry of artery frozen sections figured out that the thickness of neointima of carotid artery in miR-155 mimic group was significantly lower vs control and inhibitor groups (p&lt;0.01) at week 6. Conclusion: miR-155 transfection into VSMC seems to have reversed regulatory effect on NoxA1 expression resulting in amelioration of atherosclerotic lesion in artificial AS mouse model. A therapeutic strategy based on the functional role of miR-155 in VSMC over proliferation-based atherosclerosis would need to complementarily-synthesize miRNAs, which is a promising therapeutic tool due to the enhanced stability and sustained effects after intravenous injection in the arterial wall.

Impact of vessel curvature on neointimal healing after stent implantation as assessed by optical coherence tomography.

Purpose:Previous studies have indicated that stent implantation could alter the vessel geometry, which may impact the neointimal healing process. Curvature is an important parameter for evaluating vessel geometry. The purpose of our study was to investigate the relationship between vessel curvature and neointimal healing after stent implantation.Methods:Fifty-nine patients with acute coronary syndrome (ACS) who underwent stent implantation were enrolled in the study. According to the post-percutaneous coronary intervention vessel curvature measured by quantitative coronary angiography, patients were divided into high (n = 30) and low (n = 29) curvature groups. Neointimal thickness and area together with the neointimal type were assessed by optical coherence tomography at a 6-month follow-up.Results:Baseline clinical characteristics were comparable between the 2 groups. The vessel curvature at pre- and 6-month follow-up was significantly higher in the high curvature group than the low curvature group. At 6-month follow-up, neointimal thickness (0.22 [0.08–0.32] mm vs. 0.10 [0.07–0.16] mm, P = .043) and neointimal area (1.86 [0.66–2.66] vs. 0.82 [0.60–1.41] mm2, P = .030) were significantly higher in the high curvature group than the low curvature group. In the high curvature group, the incidence of the heterogeneous neointimal type was higher than that in the low curvature group (50.00% vs. 17.20%, respectively, P = .004), whereas the frequency of the homogeneous neointimal type was lower (43.30% vs. 82.80%, respectively, P = .004) in the high curvature group than the low curvature group.Conclusion:Higher vessel curvature after stent implantation may potentially have an impact on the neointimal healing with a higher incidence of heterogeneous neointimal.

Randomised trial of the comparison of drug-eluting stents in patients with diabetes: OCT DES trial

BackgroundTo date, there have been limited comparisons performed between everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in patients with diabetes mellitus (DM). The objectives of this study was to assess...

First serial optical coherence tomography assessment at baseline, 12 and 24 months in STEMI patients treated with the second-generation Absorb bioresorbable vascular scaffold

The aim of the study was to assess the vascular healing response after Absorb bioresorbable vascular scaffold (BVS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) utilising truly serial optical coherence tomography (OCT) examination at baseline, 12 and 24 months. This was a single-centre, prospective, longitudinal study with baseline, 12- and 24-month OCT evaluation of 18 STEMI patients treated with 22 Absorb BVS. The healing pattern was evaluated based upon lumen area, neointimal hyperplasia, strut coverage and apposition. The lumen area decreased at 12 months compared to baseline (8.52±1.69 mm² vs. 7.0±1.70 mm², p<0.01), but it did not change from that point onwards up to 24 months (7.0±1.70 mm² vs. 6.94±1.65 mm², p=0.92). At 12 months after the index procedure, the mean neointimal thickness was 217±69 μm and further neointimal hyperplasia was observed between 12 and 24 months though less pronounced (Δ62±44 μm, p<0.0001). Full circumferential coverage of the vessel wall by neointima was observed in 92% of frames at 24 months. The low number of malapposed struts at the index procedure (<5%) further decreased over the observation period and was found in only one patient at 12 and 24 months. The ratio of uncovered struts was low at both 12 and 24 months. This serial OCT analysis of the second-generation everolimus-eluting BVS in a STEMI population confirmed a favourable healing pattern as expressed by moderate neointimal growth, preserved lumen area and no late acquired malapposition.

Randomised comparison of vascular response to biodegradable polymer sirolimus eluting and permanent polymer everolimus eluting stents: An optical coherence tomography study

BackgroundDrug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. MethodsWe compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months. ResultsA total of 39 patients were randomised to BP-SES (n=19) or PP-EES (n=20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n=2889; PP-EES, n=3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p=0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8μm vs. 80±14.6μm, p=0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p=0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES (p=0.31) of neointimal regions. ConclusionThe present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.