- Effect of drug-coated balloon angioplasty on in-stent restenotic coronary lesions analyzed with optical coherence tomography and serial coronary artery angioscopy. [Journal Article]
- HVHeart Vessels 2019 Jun 15
- Drug-coated balloon angioplasty (DCBA) has been recognized for its utility in preventing in-stent re-restenosis (ISR); however, imaging of the neointima immediately after treatment and during follow-…
Drug-coated balloon angioplasty (DCBA) has been recognized for its utility in preventing in-stent re-restenosis (ISR); however, imaging of the neointima immediately after treatment and during follow-up has only been described in a few case reports. This study aimed to determine the efficacy and mechanism of the DCBA using imaging studies both immediately after the DCBA and during the follow-up period. We enrolled 15 consecutive patients who underwent DCBA for in-stent restenosis (ISR). The in-stent neointimal volume was evaluated using optical coherence tomography (OCT), and the in-stent yellow grade was assessed using coronary angioscopy (CAS) immediately after DCBA and during the median follow-up period of 9 (8-15) months. The neointimal volume was significantly reduced from 77.1 ± 36.2 mm3 at baseline to 60.2 ± 23.9 mm3 immediately after DCBA (p = 0.0012 vs. baseline) and to 46.7 ± 21.9 mm3 during the follow-up (p = 0.0002 vs. post DCBA). The yellow grade of the residual plaques at the ISR lesion, which indicated plaque vulnerability, was significantly decreased in the follow-up CAG (from baseline: 1.79 ± 1.03, during the follow-up: 0.76 ± 0.82; p < 0.0001). These data suggest that DCBA may inhibit neointimal formation and provide angioscopic intimal stabilization for ISR lesions.
- Vascular response to paclitaxel-eluting nitinol self-expanding stent in superficial femoral artery lesions: post-implantation angioscopic findings from the SHIMEJI trial (Suppression of vascular wall Healing after IMplantation of drug Eluting peripheral stent in Japanese patients with the Infra inguinal lesion: serial angioscopic observation). [Journal Article]
- IJInt J Cardiovasc Imaging 2019 Jun 14
- The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients…
The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients who received Zilver PTX stent implantation from five centers were enrolled. We performed angioscopic examinations at 2, 6, and 12 months after implantation and evaluated neointimal coverage (NIC) grade, intra-stent thrombus (IS-Th) grade, and presence of yellow plaque. NIC grade 0 was defined as stent struts exposed; grade 1, struts transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; and grade 3, struts fully embedded and invisible. IS-Th was graded as follows: grade 0 (none), 1 (focal), and 2 (diffusely spread). Angioscopic follow-up evaluation was performed at 2 months (25 patients, 42 lesions), 6 months (18 patients, 23 stents), and 12 months (14 patients, 24 stents) after stent implantation. Dominant NIC grade significantly increased over time; however, 16.3% of the cases had NIC grade 1 or 2 at 12 months. IS-Th grade decreased; however IS-Th and yellow plaque were persistently observed in 62.5% and 83.3% cases, respectively, at 12 months. An ongoing healing response was observed at 12 months after implantation; however, thrombogenic findings were noted. Prolonged dual antiplatelet therapy could potentially enhance the clinical utility of Zilver PTX.
- A prospective, multicenter, randomized OCT study of early neointimal condition at first and second months after BuMA Supreme stent versus XIENCE stent implantation in high-bleeding-risk coronary artery disease patients: study protocol for a randomized controlled trial. [Journal Article]
- TTrials 2019 Jun 07; 20(1):335
- CONCLUSIONS: The results will provide the first accurate imaging evidence on neointimal formation of the BuMA Supreme stent and the Xience stent at 1-2 months post PCI. The result should inspire further exploration and adjustment of DAPT treatments.
- LncRNA GAS5 regulates vascular smooth muscle cell cycle arrest and apoptosis via p53 pathway. [Journal Article]
- BBBiochim Biophys Acta Mol Basis Dis 2019 Jun 02
- Vascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) …
Vascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) are a class of gene regulators functioning through various mechanisms in physiological and pathological conditions. By using cultured VSMC and rat carotid artery balloon injury model, we found that lncRNA growth arrest specific 5 (GAS5) serves as a negative regulator for VSMC survival in vascular remodeling. By manipulating GAS5 expression via adenoviral overexpression or short hairpin RNA knockdown, we found that GAS5 suppresses VSMC proliferation while promoting cell cycle arrest and inducing cell apoptosis. Mechanistically, GAS5 directly binds to p53 and p300, stabilizes p53-p300 interaction, and thus regulates VSMC cell survival via induction of p53-downstream target genes. Importantly, local delivery of GAS5 via adenoviral vector suppresses balloon injury-induced neointima formation along with an increased expression of p53 and apoptosis in neointimal SMCs. Our study demonstrated for the first time that GAS5 negatively impacts VSMC survival via activation the p53 pathway during vascular remodeling.
- CXC chemokine ligand 12 (CXCL12) in atherosclerosis: An underlying therapeutic target. [Review]
- CCClin Chim Acta 2019 May 27; 495:538-544
- CXC chemokine ligand 12 (CXCL12) is a specific chemokine ligand and plays a significant role in cell chemotaxis. Upon binding to CXC chemokine receptor 4 (CXCR4) or CXCR7, CXCL12 can activate differe…
CXC chemokine ligand 12 (CXCL12) is a specific chemokine ligand and plays a significant role in cell chemotaxis. Upon binding to CXC chemokine receptor 4 (CXCR4) or CXCR7, CXCL12 can activate different signaling cascades to regulate cell proliferation, migration, and metabolism. CXCL12 exerts a pro-atherogenic action by aggravating multiple pathogenesis of atherogenesis, including dyslipidemia, inflammation, neointima hyperplasia, angiogenesis, and insulin resistance. Serum CXCL12 levels are also markedly increased in patients with atherosclerosis-associated disease. The present review focuses on recent advances in CXCL12 research in the pathogenesis of atherosclerosis together with its clinical values. This may provide insight into potential novel therapies for atherosclerosis.
- Exosomes derived from M1 macrophages aggravate neointimal hyperplasia following carotid artery injuries in mice through miR-222/CDKN1B/CDKN1C pathway. [Journal Article]
- CDCell Death Dis 2019 May 29; 10(6):422
- The role of M1 macrophages (M1M)-derived exosomes in the progression of neointimal hyperplasia remains unclear now. Using a transwell co-culture system, we demonstrated that M1M contributed to functi…
The role of M1 macrophages (M1M)-derived exosomes in the progression of neointimal hyperplasia remains unclear now. Using a transwell co-culture system, we demonstrated that M1M contributed to functional change of vascular smooth muscle cell (VSMC). We further stimulated VSMCs with exosomes isolated from M1M. Our results demonstrated that these exosomes could be taken up by VSMCs through macropinocytosis. Using a microRNA array assay, we identified that miR-222 originated from M1M-derived exosomes triggered the functional changes of VSMCs. In addition, we confirmed that miR-222 played a key role in promoting VSMCs proliferation and migration by targeting Cyclin Dependent Kinase Inhibitor 1B (CDKN1B) and Cyclin Dependent Kinase Inhibitor 1C (CDKN1C) in vitro. In vivo, M1M-derived exosomes significantly aggravated neointima formation following carotid artery ligation injury and wire injury and these effects were partly abolished by miR-222 inhibitor 2'OMe-miR-222. Our findings thus suggest that exosomes derived from M1M could aggravate neointimal hyperplasia through delivering miR-222 into VSMCs. Future studies are warranted to validate if the post-injury vascular neointimal hyperplasia and restenosis could be attenuated by inhibiting miR-222.
- Wild-type p53-induced phosphatase 1 promotes vascular smooth muscle cell proliferation and neointima hyperplasia after vascular injury via p-adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin complex 1 pathway. [Journal Article]
- JHJ Hypertens 2019 May 20
- CONCLUSIONS: Wip1 promotes VSMC proliferation and neointima hyperplasia after wire injury via affecting AMPK/mTORC1 pathway.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
- Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases. [Journal Article]
- STSemin Thromb Hemost 2019 May 16
- Ultrasound (US) imaging of heart and major arteries and veins is among the most frequently used diagnostic techniques applied in humans. Conventional cardiovascular US sessions include anatomical B-m…
Ultrasound (US) imaging of heart and major arteries and veins is among the most frequently used diagnostic techniques applied in humans. Conventional cardiovascular US sessions include anatomical B-mode and functional M-, pulsed-wave- and Doppler mode, which have their limitations in both precise cardiac chambers' delineation and small vessel imaging. The introduction of contrast-enhanced US, employing microbubble suspensions as contrast agent, has enabled a better delineation of heart chambers, the visualization of myocardial microvasculature, and the atherosclerotic plaque neovascularization. Moreover, specific disease-related molecular tracers have been developed by modifying the microbubbles with targeting ligands directed to biological markers exposed to the luminal side of the blood vessels. Microbubble functionalization has enabled in vivo molecular US imaging of various stages of atherosclerosis, from plaque initiation to plaque vulnerability, and neointima formation following revascularization procedures. Furthermore, oscillating microbubbles have been used to mechanically dissolve thrombus material and may act as carriers of drugs and nucleic acids that are released locally by US pulses. This review article summarizes recent advances in functional and molecular US images and discusses therapeutic applications of microbubbles. The addressed topics include an overview on microbubble formats, microbubble detection methods, molecular targets of cardiovascular diseases, and the use of microbubbles for thrombolysis and drug delivery.
- Functional remodeling of an electrospun polydimethylsiloxane-based polyether urethane external vein graft support device in an ovine model. [Journal Article]
- JBJ Biomed Mater Res A 2019 May 16
- Saphenous vein graft (SVG) failure rates are unacceptably high, and external mechanical support may improve patency. We studied the histologic remodeling of a conformal, electrospun, polydimethylsilo…
Saphenous vein graft (SVG) failure rates are unacceptably high, and external mechanical support may improve patency. We studied the histologic remodeling of a conformal, electrospun, polydimethylsiloxane-based polyether urethane external support device for SVGs and evaluated graft structural evolution in adult sheep to 2 years. All sheep (N = 19) survived to their intended timepoints, and angiography showed device-treated SVG geometric stability over time (30, 90, 180, 365, or 730 days), with an aggregated graft patency rate of 92%. There was minimal inflammation associated with the device material at all timepoints. By 180 days, treated SVG remodeling was characterized by minimal/nonprogressive intimal hyperplasia; polymer fragmentation and integration; as well as the development of a neointima, and a confluent endothelium. By 1-year, the graft developed a media-like layer by remodeling the neointima, and elastic fibers formed well-defined structures that subtended the neo-medial layer of the remodeled SVG. Immunohistochemistry showed that this neo-media was populated with smooth muscle cells, and the intima was lined with endothelial cells. These data suggest that treated SVGs were structurally remodeled by 180 days, and developed arterial-like features by 1 year, which continued to mature to 2 years. Device-treated SVGs remodeled into arterial-like conduits with stable long-term performance as arterial grafts in adult sheep.
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- In vivo endothelialization and neointimal hyperplasia assessment after angioplasty of sheep carotid artery with a novel polycarbonate polyurethane patch. [Journal Article]
- JBJ Biomater Appl 2019 May 14; :885328219849368
- The aim of this study was to compare two variants of a novel polycarbonate polyurethane prosthesis with polyethylene terephthalate (Dacron) prosthesis in an established sheep model of carotid patch a…
The aim of this study was to compare two variants of a novel polycarbonate polyurethane prosthesis with polyethylene terephthalate (Dacron) prosthesis in an established sheep model of carotid patch angioplasty. Two variants of the polycarbonate polyurethane prosthesis were used: (1) Polycarbonate polyurethane equal (PCU-e) prosthesis consisted of a multilayered porous structure with equal internal and external layers; (2) Polycarbonate polyurethane with more porous inner layers (PCU-mp) prosthesis had more porous inner layers than external layers. Carotid patch angioplasty was performed in 12 sheep: in six sheep, the PCU-e variant and in the other six sheep, the PCU-mp variant was implanted. Dacron patches were implanted in the contralateral carotid artery of all sheep as a control. Half of the animals with each polycarbonate polyurethane variant were euthanized after two weeks and the other half after eight weeks. Cellular infiltration, endothelialization, and neointimal hyperplasia were examined. All grafts were patent, and no thrombus was seen in any of the harvested arteries. The pores of all the three patch materials allowed infiltration of inflammatory cells, capillaries, and connective tissue. After eight weeks, a nearly complete endothelialization was visible in all patch groups without an obvious difference between the three patch materials. The neointima was thinner in the PCU patches (PCU-e: 56 ± 13 µm, PCU-mp: 119 ± 60 µm) when compared to Dacron patches (156 ± 64 µm) after two weeks. After 8 weeks, a further neointimal growth was detectable, without any significant difference of neointimal thickness between the three patch materials (Dacron: 274 ± 82 µm, PCU-e: 324 ± 98 µm, PCU-mp: 235 ± 59 µm). With the novel polycarbonate polyurethane patch materials, we achieved promising functional and morphological results with 100% patency and nearly complete endothelialization. Our findings showed at least a non-inferiority of the novel polycarbonate polyurethane patch material compared to Dacron. There were no significant differences detected between the two polycarbonate polyurethane patch variants.