Constrictive Remodeling Research Articles

Significance of Nitric Oxide Derived from the Nitric Oxide Synthases System in Cardiovascular Inter-Organ Cross-Talk.

Inter-organ cross-talk contributes to the pathogenesis of various disorders, and drug development based on inter-organ cross-talk is attracting attention. The roles of nitric oxide (NO) derived from the NO synthases system (NOSs) in inter-organ cross-talk remain unclear. We have investigated this issue by using our mice deficient in all three NOSs (triple n/i/eNOSs-/- mice). We reported that 2/3 nephrectomized triple n/i/eNOSs-/- mice die suddenly because of early onset of myocardial infarction, suggesting the protective role of NO derived from NOSs in the cross-talk between the kidney and the heart. We studied the role of NO derived from NOSs expressed in the bone marrow in vascular lesion formation. Constrictive arterial remodeling and neointimal formation following unilateral carotid artery ligation were prominently aggravated in wild-type mice transplanted with triple n/i/eNOSs-/- bone marrow cells as compared with those with wild-type bone marrow cells, suggesting the protective role of NO derived from NOSs in the cross-talk between the bone marrow and the blood vessel. We further investigated the role of NO derived from NOSs expressed in the bone marrow in pulmonary hypertension. The extent of pulmonary hypertension after chronic hypoxic exposure was markedly exacerbated in wild-type mice underwent triple n/i/eNOSs-/- bone marrow transplantation as compared with those underwent wild-type bone marrow transplantation, suggesting the protective role of NO derived from NOSs in the cross-talk between the bone marrow and the lung. These lines of evidence demonstrate that systemic and myelocytic NOSs could be novel therapeutic targets for myocardial infarction, vascular disease, and pulmonary hypertension. Significance Statement We demonstrated in studies with triple n/i/eNOSs-/- mice that partial nephrectomy accelerates the occurrence of myocardial infarction induced by systemic NOSs deficiency, that myelocytic NOSs deficiency aggravates vascular lesion formation after unilateral carotid artery ligation, and that myelocytic NOSs deficiency exacerbates chronic hypoxia-induced pulmonary hypertension. These results suggest that NO derived from NOSs plays a protective role in cardiovascular inter-organ cross-talk, indicating that systemic and myelocytic NOSs could be important therapeutic targets for myocardial infarction, vascular disease, and pulmonary hypertension.

An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty.

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti-stenosis drug-eluting stents face challenges due to their limited functions and long-term safety concerns, significantly compromising their therapeutic effect. Herein, a stent-free anti-stenosis drug coating (denoted as Cur-NO-Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor-peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur-NO-Gel has the capability to release NO upon β-galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur-NO-Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur-NO-Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.

Protective role of the nitric oxide synthases system in inter-organ communication

The role of the nitric oxide synthases (NOSs) system in inter-organ communication is not fully understood. We addressed this point in our mice lacking all three NOS isoforms (triple n/i/eNOSs-/- mice). We previously reported that the triple n/i/eNOSs-/- mice spontaneously develop myocardial infarction. However, it takes a long time (approximately 1 year) to develop myocardial infarction. We then revealed that 2/3-nephrectomized triple n/i/eNOSs-/- mice suddenly die due to early onset of myocardial infarction, succeeding in developing an experimentally useful model of myocardial infarction. These results suggest the protective role of NOSs in reno-cardiac communication. We next studied the role of NOSs in bone marrow cells (BM) in vascular lesion formation. Constrictive vascular remodeling and neointimal formation at 14 days after carotid artery ligation were markedly accelerated in wild-type (WT) mice transplanted with triple n/i/eNOSs-/- BM as compared with those with WT BM. These results suggest the protective role of NOSs in BM-vascular communication. We then investigated the role of NOSs in BM in pulmonary hypertension (PH). The extents of PH at 3 weeks after hypoxic exposure were markedly exacerbated in WT mice transplanted with triple n/i/eNOSs-/- BM as compared with those with WT BM, suggesting the protective role of NOSs in BM-lung communication. These lines of evidence indicate that systemic and BM NOSs may be a novel therapeutic target in MI, vascular disease, and PH.

Pleiotropic Effects of Icariside II on the Cardiovascular System: Novel Applications of Ethnopharmacology in Targeting Vascular Remodeling.

Pleiotropic Effects of Icariside II on the Cardiovascular System: Novel Applications of Ethnopharmacology in Targeting Vascular Remodeling.

Sequential numerical simulation of vascular remodeling and thrombosis in unconventional hybrid repair of ruptured middle aortic syndrome

Unconventional surgical procedures may be utilized in treating complicated middle aortic syndrome (MAS), the outcome and prognosis of which remain largely undetermined due to limited numbers and significant heterogeneity of this population. Using computational fluid dynamics (CFD) analysis, this study aimed to assess the dynamic changes of postoperative aortic flow in seeking to unveil the relationship between hemodynamics and vascular remodeling and thrombotic events. One patient with middle aortic syndrome complicated with aortic rupture was treated with hybrid repair of extra-anatomic bypass and fenestrated endovascular aortic repair. The patient was followed-up for 8 months by computational tomography angiography and Doppler ultrasound. Thoracoabdominal aortic blood flow and locations with ongoing thrombosis at 1, 3, and 6 months postoperatively were simulated and analyzed. Remodeling processes, including low wall shear-mediated constrictive remodeling of non-stented aorta, neointimal hyperplasia at suture lines, and minimal thrombosis at various locations, were evident. Meanwhile, abdominal blood flow was tri-phasic at 1 month after surgery, and was reversed and stabilized at 6 months. The distribution of newly formed thrombus vary at different follow-up stages, which were in line with the numerical simulation of thrombosis from different postoperative time points. CFD-based sequential monitoring is of promising value in capturing dynamic changes of vascular outcome.

Hemodynamic Characterization Of Pulmonary Artery Hypertension In A Rat

Introduction: Hemodynamic characterization of Pulmonary Artery (PA) hypertension helps to reveal progression of disease of pulmonary vasculature with constrictive remodeling of pulmonary arterioles, leading to right ventricle (RV) dysfunction and right sided HF failure. In this preclinical methodology article, surgical access, controlled mechanical ventilator set up and direct open chest measurements of PA hypertension is described, employing a rat model. Chronic PA injury was induced by single dose of monocrotaline (MCT).
 Methods & Aims: Setting of controlled mechanical volume ventilation (CMVV) was adjusted to limit its influence on RV preload and LV afterload in the instance of chronic pulmonary disease. Volume-ventilation setting of tidal volume and respiration rate was based on body weight. Isoflurane monoanesthesia was used without any premedication. PA pressures were compared using single and dual pressure catheter at 3-weeks post injury. Initially, single pressure catheter was positioned in the PA to assess data quality, while advanced data comparison (RV and PA pressures) during PA hypertension were made using dual pressure catheter. PA access was performed using “high” RV needle-stab, adjacent to the anatomical area of the PA outflow.
 Results: Introduction of single pressure catheter was successful and collected data during RV systole and diastole did not produce any major pressure artefacts. Final position in the main PA was guided by using visual cues i.e. distance of pressure sensor on the catheter, accompanied by simultaneous data recording from that location. In case of dual pressure catheter, RV and PA pressure data were successfully collected. During PA hypertension, systolic ranges were (41-52 mmHg) vs. naive (25-30 mmHg); diastolic (21-27 mmHg) vs. (9-14 mmHg); n=4. In PA hypertension, high afterload pressures complicated RV ejection, with PAP cresting about 1mmHg higher than the maximal RVP. During further assessment, RV ejection was complicated by higher PA dicrotic notch pressures, at the end of systole; for hypertension (37-41 mmHg) vs. naïve (16-21mmHg), n=4.
 Conclusions: This study revealed that good rat pressure data could be collected from the main trunk of PA using an open chest supported by CMVV. In future, hemodynamic influence of respiratory pump in close chest setting and its influence on chronic PA hypertension needs to be analyzed using solid state pressure catheter. To accomplish this, pressure catheter design should be based on rat’s RV and its outflow anatomy.

Типы и стадии сосудистого ремоделирования при контрактуре Дюпюитрена (анализ 506 артерий в операционном материале 111 пациентов)

Purpose Analysis of the severity and staging of pathomorphological changes in the arteries of palmar aponeurosis in patients with Dupuytren's contracture of different age groups Materials and methods Analysis of case records of patients younger than 50 years old (n = 19, group 1), from 50 to 65 years old (n = 60, group 2) and over 65 years old (n = 32, group 3). Light microscopy of paraffin sections of palmar aponeurosis fragments resected in partial fasciectomy and histomorphometry of palmar aponeurosis arteries of three calibers: small (outer diameter less than 150 microns), medium (150–300 microns), large (more than 300 microns). Control samples – fragments of the aponeurosis of three patients younger than 50 years old with hand injuries. Results Groups 1–3 arecomparable in terms of fibromatosis duration, frequency of lesions in both hands, and the number of fingers with impaired function, but in group 3 the frequency of contractures in advanced stages and cardiovascular diseases was higher (p less 0.05). In arteries of small caliber, obliterating lesions and signs of expansive remodeling were also encountered; in arteries of medium caliber, expansive remodeling prevailed; in arteries of large caliber, constrictive remodeling was expressed. Discussion The types of remodeling identified were found in all age groups. Based on the results of the study and the data obtained earlier, 6 stages of pathomorphological changes in the vessels of the palmar aponeurosis were identified in Dupuytren's contracture. Conclusion Dupuytren's contracture refers to diseases mediated by vascular remodeling, affecting mainly the arterial bed, the severity and staging of which does not depend on the age of a patient

The Development of Cardiac Allograft Vasculopathy Occurs in Early Intimal Thickening and Constrictive Remodeling in Long-Term Period; Long-Term Serial Intravascular Ultrasound Study

The development of cardiac allograft vasculopathy (CAV) is known to be induced by a biphasic process involving early intimal thickening and late constrictive remodeling. However, change of intimal thickening long-term period post heart transplantation (HTx) is still unknown. Our aim of this study was to investigate the change of intimal thickening of CAV long-term period post-HTx. Intravascular ultrasound (IVUS) of coronary arteries were performed at 5 to 12 weeks after HTx (baseline) and repeated annually in all HTx recipients. And we reviewed the medical records of consecutive 102 HTx recipients who underwent serial intravascular ultrasounds from baseline to at least 1-year post HTx. 'Progressive intimal thickening on IVUS' was defined as an annual increase in maximal intimal thickness (MIT) of 0.3 mm or greater. The development of CAV included the any coronary revascularization, acute myocardial infarction and the coronary artery lesions classified ISHLT CAV 1 or 2. The progressive intimal thickening on IVUS was high incidence by 3 years post-HTx, however, was low after 3 years post-HTx (Figure 1). Also, similar trends were shown regardless of initiation of everolimus. The incidence of progressive intimal thickening on IVUS was higher in the early period than in the mid-term period (92.3% vs 25.0%, P<0.001). While, cumulative event free rate of the development of CAV was linearly decreasing until 10 years after HTx (Figure 2). This long-term serial IVUS study supported that lumen loss on CAV occurred in a biphasic process consisting of the early intimal thickening and late constrictive remodeling. These results suggest that interventions to suppress an increase in intimal thickening is earlier needed within 3 years post-HTx, and also further treatment strategy to suppress the late constrictive remodeling on CAV are required.

Heterogeneous and dynamic lumen remodeling of the entire infrainguinal vein bypass grafts in patients

ObjectiveTo examine the regional variation and temporal change in lumen size along the entire autogenous vein bypass graft used for treating arterial occlusive disease in lower extremity and to explore the factors associated with graft expansive or constrictive remodeling. MethodsPatients were prospectively scanned using contrast-enhanced computed tomography at 1 week and 1, 6, and 12 months postoperatively to obtain lumen cross-sectional areas at 1-mm intervals along the entire grafts. Graft lumen remodeling characteristics and the associated demographic and clinical factors were examined. ResultsFifty-six patients with at least two consecutive computed tomography scans were analyzed. Patients with a composite or longer graft, or with diabetes, had a larger lumen cross-sectional area variation along the graft. The mean lumen cross-sectional areas of all the grafts demonstrated no significant changes through 12 months. However, individually, graft remodeling was time dependent and there was a more dramatic change in lumen cross-sectional area within the first postoperative month. At 12 months, a near equal distribution between expansive and constrictive grafts existed. A negative relation between the initial lumen diameters and the subsequent lumen diameter changes was observed. Eleven grafts failed within 12 months; failed and patent grafts had similar mean lumen cross-sectional areas at all four time points, but failed grafts had a larger maximal local cross-sectional area reduction from 1 week to 1 month (58.0 ± 6.7% vs 38.1 ± 3.1%, mean ± standard error of the mean, failed vs patent, P = .004). Black patients had a smaller mean lumen cross-sectional area than white patients at all four time points and also had a higher early percent mean area reduction (−20.5 ± 6.3% vs −1.0 ± 3.7%, black vs white, P = .018). Cilostazol use was associated with early expansive graft remodeling. ConclusionsVein grafts remodel heterogeneously and dynamically. Remodeling is associated with initial graft lumen size, race, and cilostazol use. It is found that remodeling that produces some critical minimum area or maximal percent reduction during the first postoperative month may predispose to vein graft failure. These findings offer insight into further investigation to examine the underlying mechanisms and opportunities to improve graft remodeling and durability.

Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator.

Constrictive vascular remodeling limiting blood flow, as well as compensatory outward remodeling, has been observed in many cardiovascular diseases; however, the underlying mechanisms regulating the remodeling response of the vessels remain unclear. Plasminogen activators (PA) are involved in many of the processes of vascular remodeling. We have shown previously that increased levels of tissue-type PA (tPA) contributes to outward vascular remodeling. To elucidate the mechanisms involved in the induction of outward remodeling we characterized changes in the expression profiles of 8799 genes in injured rat carotid arteries 1 and 4 days after recombinant tPA treatment compared to vehicle. Periadventitial tPA significantly increased lumen size and vessel area, encompassed by the external elastic lamina, at both one and 4 days after treatment. Among 41 differentially expressed known genes 1 day after tPA application, five genes were involved in gene transcription, five genes were related to the regulation of vascular tone [for example, thromboxane A2 receptor (D32080) or non-selective-type endothelin receptor (S65355)], and eight genes were identified as participating in vascular innervation [for example, calpain (D14478) or neural cell adhesion molecule L1 (X59149)]. Four days after injury in tPA-treated arteries, four genes, regulating vascular tone, were differentially expressed. Thus, tPA promotes outward arterial remodeling after injury, at least in part, by regulating expression of genes in the vessel wall related to function of the nervous system and vascular tone.

Morphophysiological characteristics of skin microcirculation types in patients with Dupuytren’s contracture

Aim– to investigate the patterns of cutaneous microcirculation and their relationship with structural vascular changes in palmar hypoderm in patients with Dupuytren’s disease.Material and methods. In 26 patients with Dupuytren’s contracture aged between 45 and 70 years, the microcirculation of palmar skin was assessed before the planned surgical treatment using ultrasound pulsed Doppler (Minimax-Doppler K, SP Minimax, St. Petersburg, Russia) with a high-frequency sensor of 20 MHz and laser Doppler flowmetry (BLF21, Transonic Systems Inc., USA). The local 3-minute arterial ischemic test was performed in all patients by putting the occlusion cuff on the forearm. Histological analysis of intra-operative tissue specimens was done using light microscopy (Carl Zeiss Primo Star microscope with 3.1 MP UCMOS video camera) MicroCapture Ver 6.6 program was used for data acquisition.Results. The normocirculatory type of hemodynamics (1) was found in 17 % of observations; hyperemic (2) – in 19 %, congestive-spastic (3) – in 42 %, and congestive-static (4) – in 21 %. Histologically type 1 was characterized with initial signs of constrictive arterial remodeling and capillary occlusion, 2 – with marked hyperemia of the microcirculatory bed and diapedesis of blood cells, inflammatory perivascular infiltrates, 3 – with significant narrowing and deformations of lumens in small arteries and hyalinosis of arterioles, 4 – with pronounced polymorphism of capillary loops, significant changes in arteries and veins.Discussion. Hyperemic type of microcirculation reflects high activity of autoimmune inflammation. Congestic-spastic type indicates a significant decrease in the reactivity of precapillary microvessels. Congestic-stasic type is accompanied by the most pronounced constrictive vascular remodeling and denervation of the vascular bed.Conclusion. Dupuytren’s contracture is characterized with predominance of pathological types of microcirculation in palmar skin, which must be taken into account in individualized protocols of additive therapy.

233 - Macrophages as delivery vehicles of antioxidant enzyme nanoparticles payload

Background Cardiovascular disease (CVD) is the leading cause of death in the United States, with approximately 1 in 4 deaths being attributed to a cardiovascular event. CVD often results from the development of atherosclerosis. Balloon angioplasty, a common surgical intervention to treat severe atherosclerosis often fails as a consequence of vessel renarrowing or restenosis, secondary to constrictive remodeling and neointimal hyperplasia (NIH). Reactive oxygen species are key drivers of NIH. After surgical intervention macrophages are recruited to the vasculature, providing a strategy for targeted delivery of therapeutics. Therefore, we hypothesize that macrophages can be loaded with antioxidant enzyme nanoparticles (NP) to be used as delivery vehicles of enzymatically active catalase or SOD. Methods Nanoparticle diameter was determined using dynamic light scattering (DLS) and nanotracking analysis (NTA). Bone marrow derived macrophages (BMDM) were isolated from male Zucker rats. Loading and release of antioxidant enzymes, catalase or superoxide dismutase (SOD), into BMDM or RAW 264.7 macrophages was assessed using enzyme activity assays, fluorescent spectroscopy and epifluorescent imaging. Results Catalase nanoparticles obtained were monodisperse with a diameter of 125.2 ± 3.8 nm (NTA). CuZnSOD nanoparticles were polydisperse with an average diameter of 145.1 ± 20.6 nm (NTA). NP-encapsulated enzymes were stable for 7 days with no change in activity. Uptake of antioxidant nanoparticles by murine macrophages (RAW 264.7) peaked at 2 hours with 40-50% of cells engulfing fluorescein labeled nanoparticles. Release of labeled nanoparticles was continuous over five days with a large amount (50%) of polymer release during the first 24 hours. Uptake of NP-encapsulated enzymes significantly increased internal catalase or SOD activity in RAW macrophages. Conclusion Treatment of macrophages with antioxidant enzyme nanoparticles is a viable approach to load and deliver catalytically active catalase and/or SOD providing a feasible platform for a targeted delivery system to the injured vasculature.

Assessment of palmar subcutaneous tissue vascularization in patients with Dupuytren's contracture.

AIMTo investigate the structural and functional characteristics of palmar hypodermal tissue vascularization in Dupuytren’s contracture patients of different age groups.METHODSEighty-seven Dupuytren’s contracture patients underwent partial fasciectomy. Twenty-two of them were less than 55 years old (Y-group, n = 22); the others were 55 and older (O-group, n = 65). In surgically excised representative tissue samples, a histomorphometric analysis of the perforating arteries of the palmar aponeurosis and stereologic analysis of hypodermis vascularity were performed. The method of laser flowmetry estimated the microcirculation of the skin of the palm.RESULTSFrequency of cases with rapid development of contracture (less than 5 years) was 13.6% in the Y-group and 40% in the O-group, P < 0.05. The external and luminal diameters of perforating arteries in palmar fascia were decreased more severely in Y. The thickness of intima increased three times compared with healthy control, and the intima/media relation also increased, especially in O. Increased numerical and volumetric micro-vessel densities in hypodermis, percentage of large vessels (more than 12 μm in diameter), and percentage of vessels with signs of periadventitial inflammatory infiltration were noted in Y. The percentage of vessels with adventitial fibrosis was greater in O than in Y. Base capillary flow in Y was increased compared to healthy control subjects and to O, and peak capillary flow was increased in comparison with control.CONCLUSIONCompared to the O-group, Y-group patients exhibited more severe constrictive remodeling of palmar fascia perforating arteries supplying hypodermis but more expressed compensatory changes of its capillarization.

CRT-200.14 The Use Of Bioresorbable Scaffold Stent for Treatment of Peripheral Vascular Disease

Drug-eluting stents have been used for treatment of peripheral vascular disease of patients with symptoms refractory to optimal medical therapy. Novel stents using bioresorbable vascular scaffolds (BVS) can overcome the constrictive remodeling and natural endothelial elastic recoil. We aimed to

Attenuation of Maladaptive Responses in Aortic Adventitial Fibroblasts through Stimuli-Triggered siRNA Release from Lipid-Polymer Nanocomplexes.

Lipid-siRNA assemblies are modified with photo-responsive polymers to enable spatiotemporally-controlled silencing of interleukin 1 beta (IL1β) and cadherin 11 (CDH11), two genes that are essential drivers of maladaptive responses in human aortic adventitial fibroblasts (AoAFs). These hybrid nanocomplexes address the critical challenge of locally mitigating fibrotic actions that lead to the high rates of vascular graft failures. In particular, the lipid-polymer formulations provide potent silencing of IL1β and CDH11 that is precisely modulated by a photo-release stimulus. Moreover, a dynamic modeling framework is used to design a multi-dose siRNA regimen that sustains knockdown of both genes over clinically-relevant timescales. Multi-dose suppression illuminates a cooperative role for IL1β and CDH11 in pathogenic adventitial remodeling and is directly linked to desirable functional outcomes. Specifically, myofibroblast differentiation and cellular proliferation, two of the primary hallmarks of fibrosis, are significantly attenuated by IL1β silencing. Meanwhile, the effects of CDH11 siRNA treatment on differentiation become more pronounced at higher cell densities characteristic of constrictive adventitial remodeling in vivo. Thus, this work offers a unique formulation design for photo-responsive gene suppression in human primary cells and establishes a new dosing method to satisfy the critical need for local attenuation of fibrotic responses in the adventitium surrounding vascular grafts.

Possible mechanical causes of scaffold thrombosis: insights from case reports with intracoronary imaging.

The advent of intracoronary stents has greatly increased the safety and applicability of percutaneous coronary interventions. One of the drawbacks of drug-eluting stents (DES) is the increased risk of late and very late stent thrombosis (ST). It was anticipated that the risks of ST after DES implantation would be solved with the advent of fully biodegradable scaffolds, which offer the possibility of transient scaffolding of the vessel to prevent acute vessel closure and recoil while also transiently eluting an antiproliferative drug to counteract constrictive remodelling and excessive neointimal hyperplasia. In spite of the enthusiasm for the concept of bioresorbable scaffolds, current clinical data on the Absorb bioresorbable vascular scaffold (BVS) have generated concerns about scaffold thrombosis (ScT) in both the early and late phases. However, the causes of ScT in both the early and late phases have yet to be fully elucidated. This article seeks to provide insights into the possible mechanical causes of ScT in the early and late phases with data stemming from intracoronary imaging (intravascular ultrasound and optical coherence tomography) of the currently published ScT cases following the implantation of BVS and reviews the practical recommendations for implantation of the BVS made by a group of experts.

MicroRNAs

Atherosclerosis is an inflammatory disease involving, among others, production and degradation of the extracellular matrix and the accumulation of lipids in the arterial wall. Matrix metalloproteinases (MMPs) are the main physiological mediators of matrix degradation, capable of degrading extracellular matrix components such as collagens, proteoglycans, elastin, laminin, fibronectin, and other glycoproteins. The actions of MMPs could potentially be modulated with different approaches: (1) inhibition of MMP expression and protein synthesis, (2) inhibition of MMP activation, and (3) inhibition of MMP activity.1 Although subject for studies for many years, including the development of more specific inhibitors for different MMP family members such as MMP-8 and MMP-12, opportunities as useful therapeutic targets in clinical studies are still hampered. The effect of broad-spectrum MMP inhibitors has been studied in models of vascular injury in large animal studies with varying outcomes. MMP inhibition results in impaired constrictive remodeling after balloon angioplasty2 but fails to inhibit in stent neointima formation.3 Interfering with MMP activity has been a popular approach to attenuate atherosclerotic disease in animal models, but translation to human disease is cumbersome. There are many reasons to explain this failure in translation: expression patterns of MMPs and TIMPs (tissue inhibitor of metalloproteinases) in mouse and human macrophages differ, and the lack of adequate preclinical models is evident. In addition, the widespread functional relevance of MMPs in human biology hamper clinical application because of side effects.4 However, currently clinically applied drugs …

PP095 Assessment Of Magmaris Resorbable Metal Stent In Patients With Angina

INTRODUCTION:Ischaemic heart disease is the leading cause of death worldwide. Magmaris™ is a new drug-eluting resorbable stent used for coronary reperfusion during a balloon angioplasty. Magmaris™ is composed of absorbable magnesium scaffold and its surface is coated with bioresorbable poly-L-lactide, which incorporates Sirolimus. Magmaris™ has theoretical advantages as the stent body disappears after vascular constrictive remodeling. It would provide the stability and elasticity of non-resorbable metal stents, but without long-term problems such as endothelial dysfunction, delay in endothelialization, risk of thrombosis and complications due to long-term antiplatelet medication. The objective of this work is to assess efficacy and safety of Magmaris ™ in patients with angina or silent ischaemia.METHODS:Early assessment of Magmaris™ identified through the Early-Awareness and Alert-System, “SINTESIS-new technologies”, of The Instituto De Salud Carlos III (AETS-ISCIII). The searched databases were: MEDLINE (PubMed), EMBASE, WOS, Clinical Trials and Cochrane Library. Clinical studies using Magmaris™ published in any language until December 2016 were reviewed.RESULTS:One prospective, non-randomized, non-controlled, multicenter, clinical trial with two publications was retrieved. The first publication (123 patients) showed mainly imaging outcomes of angiography, intravascular ultrasound and tomography at 6 months of follow up. The second publication (118 patients) with data from 12 months of follow up also reported: Target lesion failure in four patients (3.4 percent; 95 percent Confidence Interval, CI:0.9–8.4); one target-vessel myocardial infarction (0.8 percent; one myocardial infarction (0.8 percent); two clinically driven target lesion revascularisation (1.7 percent) and two clinically driven target-vessel revascularisation (1.7 percent). No definite scaffold thrombosis was observed. No procedural complications were reported. This trial is expected to continue up to 36 months of follow up.CONCLUSIONS:Clinical data show that Magmaris™ seems to be an effective and safe treatment in patients with angina or silent ischaemia undergoing balloon angioplasty. More research specially randomized controlled trials are necessary to confirm these results.

Assessment of a Drug-Eluting Balloon for the Treatment of de novo Coronary Lesions Guided by Optical Coherence Tomography: Study Protocol for a Randomized Controlled Trial

Background: The drug-eluting balloon (DEB) is a promising tool to prevent restenosis after coronary angioplasty. However, data on the outcomes of DEB in de novo lesions are scarce. Vessel recoil and constrictive remodeling are the dominant causes of restenosis after angioplasty. The use of cutting balloons (CB) may effectively reduce elastic recoil after balloon dilation. In this study, we evaluate the efficacy and safety of DEB in treating de novo coronary artery lesions, using a predilation strategy with cutting balloon (CB) dilation before DEB angioplasty. Methods/Design: We present the design of a prospective, single-center, open-label, randomized, 2-arm clinical trial aiming to assess whether or not the strategy of CB dilation before DEB angioplasty reduces the primary end point of late lumen loss (LLL) compared with drug-eluting stent (DES) implantation alone for de novo coronary artery lesions. A total of 120 patients will be randomly enrolled into the DEB or DES group (1:1 ratio). The primary end point is insegment LLL at 12 months as measured by optical coherence tomography (OCT). Secondary end points include procedural success, such as angiographic success and device success, and clinical outcomes including all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization, and stent thrombosis. Discussion: The study will evaluate the clinical efficacy, angiographic outcomes, and safety of DEB after CB dilation compared with DES for the treatment of de novo coronary artery lesions guided by OCT.

Bioresorbable vascular scaffolds for the treatment of coronary artery disease: Clinical outcomes from randomized controlled trials.

The permanent metal prosthesis common to bare metal stents (BMS) as well as both first- and second-generation drug-eluting stents (DES) following treatment of coronary artery disease represents a long-lasting substrate for late adverse coronary events including restenosis, thrombosis, and neoatherosclerosis. Following resorbtion, bioresorbable scaffolds (BRS) may eliminate this nidus and improve late outcomes through restoration of the vessel to more normal vascular structure and function. BRS represents a single platform which incorporates the mechanical features of metallic stents to provide safe and effective revascularization, suppression of restenosis and prevention of constrictive remodeling with long-term restoration of the treated vessel to a more natural state. The landscape of BRS is rapidly evolving with new materials which target various performance goals for the duration of vascular support and polymer resorption time. The Absorb bioresorbable vascular scaffold (Absorb BVS), recently approved by United States Food and Drug Administration, has extensive clinical evidence to date in support of its clinical efficacy and safety. Recently published data from well-executed randomized clinical trials (RCTs) as part of the ABSORB Clinical development program along with other investigator-initiated trials provide insights into the safety and performance of this device in patients with de novo coronary lesions as well in the setting of ST-segment elevation myocardial infarction (STEMI). This review provides a comprehensive, outcomes based understanding of the available evidence from RCTs that offer head-to-head comparisons of Absorb BVS with metallic everolimus-eluting stents (EES). © 2016 Wiley Periodicals, Inc.