Development Of Restenosis Research Articles

Abstract 332: Inhibition of the Enhancer of Zeste Homolog Family Mitigates Intimal Hyperplasia in Rat Carotid Arteries

Rationale: The enhancer of zeste homologs 1 and 2 (EZH1 and EZH2) are histone-lysine N-methyltransferases that modify histones by methylation which leads to transcriptional repression. It has recently been shown that EZH1 and EZH2 play an important role in various cancers. Whether they play a role in recurrent vascular diseases is not known. Objective: We assessed whether EZH1 and EZH2 are important contributors to the development of intimal hyperplasia (IH) and restenosis. Methods and Results: Following rat carotid balloon angioplasty, EZH2 showed highest expression at day 3 post procedure and then decreased at day 7 in injured arteries, as determined by Western blotting. Change of EZH1 is less prominent. Dual inhibition of EZH1 and EZH2 through peri-adventitial administration of a selective inhibitor, UNC-1999, effectively inhibited intimal hyperplasia, with ~40% reduction in the ratio of intima to media (I/M). Moreover, in cultured primary rat smooth muscle cells (SMCs) as well as MOVAS cells, pretreatment with 5μM UNC-1999 resulted in a 60% decrease in cell proliferation and ~80% reduction of migration that were stimulated by PDGF-BB. Simultaneous knockdown of EZH1 and EZH2, as well as knockdown of their shared scaffold protein(EED), led to effective inhibition of proliferation and migration of SMCs. However, knockdown of EZH2 alone did not recapitulate the effects of dual inhibition of EZH1 and EZH2. Conclusions: This study demonstrates that dual inhibition of EZH1 and EZH2, both histone modifiers, mitigates intimal hyperplasia in vivo and attenuates PDGF-BB stimulated SMC proliferation and migration in vitro.

ASSOCIATION OF ENOS GENE POLYMORPHISMS AS A RISK FACTOR OF CORONARY IN-STENT RESTENOSIS

Background: In recent years more attention is paid to the methods of interventional treatment of coronary artery disease. However, despite the numerous clinical studies the problem of stent restenosis after interventional procedures remains an important one. The studies of the molecular mechanisms of restenosis of coronary arteries and findings for new genetically determined predictors of restenosis after stenting become vital and essential. The NO-synthase influence on the development of endothelial dysfunction is practically assured, but the studies on the NOS genes' polymorphism effect on the incidence rate of in-stent restenosis are isolated and based on a limited number of clinical observations. The determined facts demonstrate the relevance of the conducted study, the results of which formed a new understanding of the role of NO-synthase genes in the predisposition to hyper-proliferative stents in patients with coronary artery disease. Aims: Set association between the eNOS gene polymorphisms and the risk of restenosis in patients with coronary artery disease hospitalized for coronary restenosis.Materials and methods: We examined 484 patients with the verified diagnosis of the ischemic heart disease who underwent treatment at the unit of atherosclerosis and chronic coronary heart disease of «Cardiology Research Institute». Stenting of coronary arteries was performed in 210 people. The group of a restenosis enrolled 60 patients and the group without restenosis — 150. Genotyping was performed by non-enzymatic technique for isolation of genomic DNA from the venous blood of the surveyed, NOS genes' polymorphisms were detected by polymerase chain reaction (PCR). Results: The established development of in-stent restenosis was associated with the following eNOS gene polymorphisms: VNTR ― in homozygotes for the minor allele (genotype aa) and heterozygotes (genotype ab); 894G/T ― in heterozygotes (the GT genotype) and homozygotes (TT genotype).Conclusions: VNTR and 894G/T polymorphisms of eNOS gene are associated with risk for restenosis and can serve as additional markers for risk of restenosis after coronary stenting.

Transcoronary Concentration Gradient of microRNA-133a and Outcome in Patients With Coronary Artery Disease

Circulating levels of microRNA (miR)-133a are increased in patients with coronary atherosclerotic disease (CAD). Whether the cardiac release of this miR provides any prognostic information in patients with CAD is currently unknown. We aimed to investigate if changes in concentration of miR-133a trough the coronary circulation may be associated with patients' cardiovascular outcome. We enrolled 111 patients (82 with stable CAD and 29 with acute coronary syndromes [ACS]) who underwent coronary angiography. Circulating levels of miR-133a were measured across the transcoronary circulation. Major adverse cardiac events (MACE: death, nonfatal myocardial infarction, and need for revascularization) were recorded through a median follow-up of 32months. An increased transcoronary concentration gradient of miR133a showed a significant association with overall rate of MACE at follow-up in patients with both stable CAD and ACS (p= 0.011 and p= 0.002, respectively). At the single end point-analysis, increased transcoronary concentration gradients of miR133a were significantly associated with increased rate of death in patients with ACS (p=0.017) and with increased incidence of new revascularization because of in-stent restenosis in patients with stable CAD (p= 0.026). Kaplan-Meier curves showed a significantly worse event-free survival in patients with greater transcoronary gradients of miR133a (p= 0.026 in stable CAD group and p= 0.007 for ACS group). Nevertheless, these findings lost their significance after adjustment for common cardiovascular risk factor and high-sensitivity troponin-T. In conclusions, the release of miR133a, as measured by its transcoronary concentration gradient, is associated with a higher incidence of MACE in patients with CAD, but it does not add significant prognostic information compared with traditional prognostic biomarkers, therefore limiting its potential usefulness in the clinical practice. Nevertheless, the differential modulation of miR-133a release in the coronary circulation may reflect pathophysiological mechanism involved in CAD progression and complications and suggest a novel potential role for this miR in the development of in-stent restenosis.

Relationship between the Level of Circulating CD45+ Platelets and Development of Restenosis after Implantation of Drug-Eluting Stents to Patients with Coronary Heart Disease.

The study was carried out in 126 patients with stable angina pectoris, who underwent elective coronary artery stenting with drug-eluting stents and follow-up angiography within 6-12 months thereafter. Five significant risk factors of restenosis were identified by binary comparisons of different variables. The logistic regression equation that included the level of CD45-positive platelets, diabetes, small vessel stenting, number of simultaneously implanted stents in one patient, and lesion length demonstrates the highest level of prediction of in-stent restenosis (OR=22.8; p<0.001). ROC-analysis demonstrated high prognostic value of the logit model (area under ROC curve 0.87, p<0.001). The data suggest that a close relationship exists between the development of restenosis and the level of circulating CD45+ platelets.

10-Year Clinical Outcome After Randomization to Treatment by Sirolimus- or Paclitaxel-Eluting Coronary Stents

BackgroundFirst-generation drug-eluting coronary stents (DES) were introduced in 2003 to 2004, and their use resulted in a considerable reduction in the development of in-stent restenosis at the cost of an increased risk of late stent thromboses. ObjectivesThis study followed clinical outcomes of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention. MethodsA total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES implanted. This study recorded the occurrence of a major adverse cardiac event (MACE) assessed as the composite of cardiac death, myocardial infarction, and target vessel revascularization. Stent thromboses were also assessed. ResultsOf the 2,098 unselected patients, 73.1% were still alive after 10 years. During the follow-up period, MACE occurred in 346 (32.5%) in the group receiving a sirolimus-eluting stent and in 342 (33.1%) in the group receiving a paclitaxel-eluting stent (hazard ratio: 0.96; 95% confidence interval: 0.83 to 1.11; p = 0.60), with a steady annual rate of 2.6% after the first year. Definite, probable, and possible stent thrombosis appeared in 279 patients (13.3%), with no difference between stent types and with a steady annual rate of 1.3% after the first year. ConclusionsAmong the surviving patients, the long-term annual MACE rate and the stent thrombosis rate appeared constant for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT00388934)

Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions.

Surgical and endovascular therapies for severe atherosclerosis often fail due to the development of neointimal hyperplasia and arterial restenosis. Our objective was to synthesize, characterize, and evaluate the targeting specificity and biocompatibility of a novel systemically injected nanoparticle. We hypothesize that surface‐functionalization of gold nanoparticles (AuNPs) with a collagen‐targeting peptide will be biocompatible and target specifically to vascular injury. 13 nm AuNPs were surface functionalized with a peptide‐molecular fluorophore and targeted to collagen (T‐AuNP) or a scrambled peptide sequence (S‐AuNP). After rat carotid artery balloon injury and systemic injection of T‐AuNP or S‐AuNP, arteries and organs were harvested and assessed for binding specificity and biocompatibility. The T‐AuNP bound with specificity to vascular injury for a minimum of 24 h. No significant inflammation was evident locally at arterial injury or systemically in major organs. The T‐AuNP did not impact endothelial cell viability or induce apoptosis at the site of injury in vivo. No major changes were evident in hepatic or renal blood chemistry profiles. Herein, we synthesized a biocompatible nanoparticle that targets to vascular injury following systemic administration. These studies demonstrate proof‐of‐principle and serve as the foundation for further T‐AuNP optimization to realize systemic, targeted delivery of therapeutics to the sites of vascular injury.

High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele

BackgroundIn-stent restenosis occurs in 10–30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation.MethodsIn a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression.ResultsAverage follow-up time was 1.0 (+ − 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ − 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis.ConclusionsMBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism.

CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls.

Clopidogrel is an antiplatelet drug especially used in patients undergoing percutaneous coronary interventions (PCI). Polymorphisms within CYP2C19 can result in important interindividual variations regarding therapeutic efficacy. Therefore, we aimed to evaluate the impact of the CYP2C19⁎2 variant (rs4244285) on in-stent restenosis occurrence in Chilean patients who underwent PCI and received clopidogrel. A total of 77 cases with stenosis >50% in the angioplasty site (62.75 ± 9.8 years, 80.5% males) and 86 controls (65.45 ± 9.8 years, 72.1% males) were studied. The polymorphism was genotyped using TaqMan® Drug Metabolism Genotyping Assays. Overall, CYP2C19⁎2 allele frequency was 8.3%. Diabetes, chronic lesions, and bare metal stents (BMS) were observed more often in cases than in controls (p = 0.05, p = 0.04, and p = 0.02, resp.). Genotypic frequencies did not differ significantly between the groups (p = 0.15). Nonetheless, the mutated allele was observed in a greater proportion in patients without in-stent restenosis (p = 0.055). There was no significant association between the rs4244285 variant and the occurrence of in-stent restenosis after PCI (OR = 0.44; 95% CI: 0.19 to 1.04; p = 0.06). In summary, no association was identified between the CYP2C19⁎2 variant and the development of coronary in-stent restenosis.

Doppler Characteristics of Recurrent Hepatic Artery Stenosis.

We sought to assess midterm sonographic findings in patients after stenting for hepatic artery stenosis. Thirty-nine hepatic artery stent procedures were performed for hepatic artery stenosis after liver transplantation between September 2009 and December 2013. Thirty cases were technically successful and met the minimum follow-up time (76 days, defined by earliest diagnosed stenosis). Routine ultrasound surveillance was obtained on all patients, and statistical analysis of the findings in the patency and restenosis groups was performed. Of the 30 cases, restenosis occurred 9 times in 6 patients. Mean follow-up was 677 days. Mean time to restenosis was 267 days. Five cases (56%) were identified within the first 6 months after stent placement. Four cases (44%) were recognized in the second year after stent placement. Prior to the sonographic diagnosis of restenosis, the mean resistive indices of the main (.64 versus .57, P < .0001), left (.63 versus .54, P < .0001), right anterior (.60 versus .52, P < .0001), and right posterior (.60 versus .53, P = .001) hepatic artery branches differed among patency and restenosis groups, respectively. The mean peak systolic velocity also differed significantly between the 2 groups: 254 cm/sec in patients with eventual restenosis versus 220 cm/sec in patients without restenosis (P = .02). The sonographic evaluation of hepatic artery stenosis remains critical during the first 2 years after stent placement. While the vast majority of patients do not restenose, resistive index and peak systolic velocity differed significantly between the 2 groups and may be prognostic surveillance markers for the development of restenosis.

Clinical condition and cardiovascular risk factors displaying neoatherosclerosis in stented coronary arteries with developing restenosis

Aim. To study the significance of clinical parameters and cardiovascular risk factors (CVR) for restenosis development at long terms after percutaneous coronary intervention (PCI) as a possible displaying of neoatherosclerosis development (NA). Material and methods. Totally, 155 patients after coronary stents implantation, bare and drug eluting, who then, according to clinical profile, underwent second (follow-up) coronary arteriography (CAG) and/or PCI at the timeline of ~4 years. All patients were selected to groups according to restenosis development and time spent before the second procedure (before and after 9 months): group 1 (n=67) — short term follow-up ( 9 months) and absence of restenosis; group 4 (n=19) — long term and restenosis (probable NA). Results. Comparison of clinical data and CVR showed that hypodynamia/ abdominal obesity were more prevalent in the group 1 — 20,90%/11,94%, respectively, and group 3 — 13,95%/11,63%, than in group 4 — 5,26%/5,26% and were completely absent in group 2 (p=0,011). Second PCI at the follow-up was done significantly more commonly in restenosis: gr.1/gr.3 — 68,66%/58,14%, gr.2/gr.4 — 84,62%/89,47% (p=0,028). Diagnosis “acute coronary syndrome” in “follow-up CAG/PCI” was significantly more common in delayed restenosis as a display of possible NA — group 4 — 31,58%, comparing to other groups of patients: group 1 — 14,93%, group 2 — 11,54%, group 3 — 4,65% (p=0,043). Other risk factors: arterial hypertension, hypercholesterolemia, diabetes mellitus, insulin dependency, chronic renal failure, smoking, alcohol abuse, family cardiovascular anamnesis, body mass index, — did not show statistically significant differences between the groups. Conclusion. Neoatherosclerosis as the possible element of restenosis at long terms of coronary stenting, in difference from earlier restenosis, presented with more frequent acute clinical conditions. There were no significant difference by CVR factors.

Research on the relationship between physical activity status and restenosis in patients with PCI

Objective To investigate the physical activity status of patients after percutaneous coronary intervention (PCI) and to determine its potential influencing factors, then analyze the relationship between physical activity and the development of restenosis in patients with PCI. Methods A cross-sectional study was conducted among 230 patients who underwent coronary angiography review again after PCI in a tertiary hospital of Harbin, to collect their information on physical activity by using general information questionnaire and international physical activity questionnaire (IPAQ). Patients′ physical activity status was accessed; the influential factors that affect the physical activity and the relation between physical activity and restenosis in patients with PCI were analyzed. Results The physical activity of patients after PCI was in low level, and patients with inadequate physical activity accounted for 70. 4%. As a residence, city is a risk factor for lack of physical activity; married status and 10-12 months after PCI are the protective factor for lack of physical activity. The level of physical activity in restenosis group was significantly different from that in the non-restenosis group (P=0.013). Conclusions The level of physical activity in patients with PCI is low, and low-level physical activity is closely related with the restenosis. Intervention measures are warranted in patients who are living in cities, unmarried, underwent PCI for 6-9 months or 12 months. Key words: Percutaneous coronary intervention; Physical activity; Influencing factors; Restenosis

Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury.

Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in the severity of injury influenced endothelial regeneration, neointima formation, and homing of human inflammatory and progenitor cells. In contrast to non-reconstituted mice, hPBMC reconstitution reduced neointima formation after femoral cuff injury whereas hPBMCs promoted neointima formation after carotid wire injury 4 weeks after induction of injury. Neointimal endothelium and smooth muscle cells in the injured arteries were of mouse origin. Our results indicate that the immune system may differentially respond to arterial injury depending on the severity of injury, which may also be influenced by the intrinsic properties of the arteries themselves, resulting in either minimal or aggravated neointima formation.

Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress.

Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in-stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet-derived growth factor-BB (PDGF-BB) stimulation. It was found that evodiamine inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle-promoting cyclin proteins and cyclin-dependent kinases. In addition, evodiamine attenuated the PDGF-BB-induced phosphorylation of mitogen-activated protein kinases p38 and extracellular signal-regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.

Pathological analysis of a case with peri-stent contrast staining after BMS implantation

A 68-year-old female underwent bare-metal stent (BMS) implantation in the right coronary artery (RCA) for ST-segment elevation myocardial infarction. Recurrent refractory restenosis with peri-stent contrast staining (PSS) formation was observed in the stented lesion at follow-up angiography at 7, 11, and 14 months after the index stent implantation. After 2 repeated interventions, this patient was referred to coronary artery bypass grafting due to occlusion of RCA and progression of proximal left anterior descending coronary artery lesion at 15 months after stent implantation. Pathologic examination of the surgically resected specimen of stented RCA segment revealed total occlusion with dense fibrous collagenous tissue and significant inflammatory cell infiltration including scattered eosinophils. Extensive loss of medial smooth muscle layer was observed in the vessel wall, which was likely to be the cause of PSS. In the course of treatment, this patient was found to have chromium allergy with positive patch test. Allergic reactions to chromium released from the stent might be one of the triggering mechanisms for in-stent restenosis and PSS after BMS implantation.<Learning objective: Peri-stent contrast staining (PSS) was an abnormal angiographic finding suggesting presence of contrast material outside the stent border after sirolimus-eluting stent implantation. However, PSS is rarely seen with bare-metal stents (BMSs), and PSS and refractory restenosis after BMS implantation suggests the relation with metal allergy. We must think of metal allergy after the development of refractory restenosis and PSS with BMS implantation.>

Blood level of CD45+ platelets and development of restenosis after drug-eluting stent implantation in patients with stable coronary artery disease.

The aim of this study was to assess CD45-positive platelets (CD45+ platelets) involvement in restenosis development after drug-eluting stent (DES) implantation in patients with stable coronary artery disease (CAD). The study comprised 126 male and female patients with stable angina pectoris, who underwent elective coronary stenting with DES and follow-up angiography within 6-12months. The patients were assigned to the group with restenosis (n= 53) or group without restenosis (n= 73) according to the follow-up angiograms. In both groups we compared the level in blood of CD45+ platelets, the clinical, laboratory and angiographic variables, which may affect the development of restenosis. We have also constructed a logit regression model for prognosis of restenosis occurrence after DES implantation. The blood count of CD45+ platelets was higher in patients with restenosis than in patients without: 0.82 % (0.58; 1.12) vs. 0.34 % (0.20; 0.68), p< 0.001,data are expressed as median (lower quartile; upper quartile). By binary comparisons of more than 35 different clinical, laboratory and angiographic variables we identified 8 significant risk factors for the development of stent restenosis after DES. In order to define the risk of the development of restenosis, we have built a logit regression model. The resulting logit regression equation included the level of CD45+ platelets, the neutrophil to lymphocyte ratio (NLR), small diameter arteries stenting and the number of simultaneously implanted stents in one patient. Receiver operating characteristic (ROC) curve analysis has demonstrated the high prognostic value of the resulting logit regression equation with an area under the curve (AUC) of 0.91 % (p< 0.001). The acquired data indicate the presence of a close relationship between circulating CD45+ platelets and restenosis development after DES implantation in patients with stable CAD.

Blood level of CD45+ platelets and development of restenosis after drug-eluting stent implantation in patients with coronary artery disease

Blood level of CD45+ platelets and development of restenosis after drug-eluting stent implantation in patients with coronary artery disease

Computational study of the risk of restenosis in coronary bypasses.

Coronary artery disease, caused by the buildup of atherosclerotic plaques in the coronary vessel wall, is one of the leading causes of death in the world. For high-risk patients, coronary artery bypass graft is the preferred treatment. Despite overall excellent patency rates, bypasses may fail due to restenosis. In this context, the purpose of this work was to perform a parametric computational study of the fluid dynamics in patient-specific geometries with the aim of investigating a possible relationship between coronary stenosis degree and risk of graft failure. Firstly, we propose a strategy to prescribe realistic boundary conditions in the absence of measured data, based on an extension of Murray's law to provide the flow division at bifurcations in case of stenotic vessels and non-Newtonian blood rheology. Then, we carry out numerical simulations in three patients affected by severe coronary stenosis and treated with a graft, in which the stenosis degree is virtually varied in order to compare the resulting fluid dynamics in terms of hemodynamic indices potentially involved in restenosis development. Our findings suggest that low degrees of coronary stenosis produce a more disturbed fluid dynamics in the graft, resulting in hemodynamic conditions that may promote a higher risk of graft failure.

Usefulness of the monocyte-to-high-density lipoprotein cholesterol ratio to predict bare metal stent restenosis.

The aim of the present study was to investigate the predictive value of preprocedural monocyte count-to-high-density lipoprotein cholesterol ratio (MHR) on development of in-stent restenosis in patients undergoing coronary bare-metal stent (BMS) implantation. Data from 705 patients who had undergone BMS implantation and additional control coronary angiography were analyzed. Patients were divided into three tertiles based on preprocedural MHR. Restenosis occurred in 59 patients (25%) in the lowest tertile, 84 (35%) in the middle tertile and 117 (50%) in the highest MHR tertile (p < 0.001). Using multiple logistic regression analysis, smoking, diabetes mellitus, stent length, preprocedural MHR and C-reactive protein levels emerged as independent predictors of in-stent restenosis. High preprocedural MHR is related to BMS restenosis.

Wall shear stress in the development of in-stent restenosis revisited. A critical review of clinical data on shear stress after intracoronary stent implantation.

The average wall shear stress (WSS) is in 1 Pa range in coronary arteries, while the stretching effect of an implanted coronary stent can generate up to 3 × 105 times higher circumferential stress in the vessel wall. It is widely accepted that WSS plays a critical role in the development of restenosis after coronary stent implantation, but relevant clinical endpoint studies are lack-ing. Fluid dynamics modeling suggests an association between WSS and intimal hyperplasia, however, such an association is not established when the compensating healing process becomes an overshoot phenomenon. This review summarizes available clinical results and concepts of potential clinical importance.

The Relationship Between Neutrophil-Lymphocyte Ratio and Primary Patency of Percutaneous Transluminal Angioplasty in Hemodialysis Arteriovenous Fistula Stenosis When Using Conventional and Drug-Eluting Balloons.

The aim of this study is to investigate the potential association of neutrophil-lymphocyte ratio (NLR) between primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula stenosis and type (Conventional and Drug-Eluting) of balloons used in PTA. This retrospective study consists of 78 patients with significant arteriovenous fistulas stenosis who were treated with PTA by using Drug-Eluting Balloon (DEB) (n=29) or Conventional Balloon (CB) (n=49). NLR was calculated from preinterventional blood samples. All patients were classified into two groups. Group A; primary patency<12months (43/78), Group B; primary patency≥12months (35/78). Cox regression analysis and Kaplan-Meier method were used to determine respectively independent factors affecting the primary patency and to compare the primary patency for the two balloon types. NLR ratio and balloon type of the two groups were significantly different (p=0.002, p=0.010). The cut-off value of NLR was 3.18 for determination of primary patency, with sensitivity of 81.4% and specificity of 51.4%. Primary patency rates between PTA with DEB and CB displayed statistically significant differences (p<0.05). The cut-off value was 3.28 for determination of 12-month primary patency with the conventional balloon group; sensitivity was 81.8% and specificity was 81.3%. There was no statistical relation between NLR levels and the drug-eluting balloon group in 12-month primary patency (p=0.927). Increased level of NLR may be a risk factor in the development of early AVF restenosis after successful PTA. Preferring Drug-Eluting Balloon at an increased level of NLR can be beneficial to prolong patency.