Medicine and Health Sciences Commons^™

Resistant Drug-Eluting Stent Restenosis And Resurrection Of Intracoronary Brachytherapy: The Lazarus Of Contemporary Coronary Intervention, Michael P. Savage, David L. Fischman

Division of Cardiology Faculty Papers

No abstract provided.

Percutaneous Coronary Intervention Of Totally Occluded Coronary Venous Bypass Grafts: An Exercise In Futility?, Evan Nardone, Brandon M Madsen, Melissa Mccarey, D L Fischman, Nicholas Ruggiero, Paul Walinsky, Alec Vishnevsky, Michael P. Savage

Department of Medicine Faculty Papers

Background: Percutaneous coronary intervention (PCI) of diseased saphenous vein grafts (SVG) continues to pose a clinical challenge. Current PCI guidelines give a class III recommendation against performing PCI on chronically occluded SVG. However, contemporary outcomes after SVG intervention have incrementally improved with distal protection devices, intracoronary vasodilators, drug-eluting stents, and prolonged dual antiplatelet therapy.

Aim: To reassess the procedural and long-term outcomes of PCI for totally occluded SVG with contemporary techniques.

Methods: This was a retrospective observational study conducted at a single university hospital. The study population consisted of 35 consecutive patients undergoing PCI of totally occluded SVG. Post-procedure dual …

Outcomes Of Percutaneous Transluminal Angioplasty For Central Vein Stenosis In Hemodialysis: A Literature Review, Hilman Ibrahim, Akhmadu Muradi, Eka A. Limianto

The New Ropanasuri Journal of Surgery

Percutaneous transluminal angioplasty (PTA) is the mainstay treatment for central vein stenosis. However, the recurrent rate of the stenotic lesion after PTA remains high. Thus, we ran a review found on some databases. Out of thirteen articles, five articles were eligible and reviewed. Drug-coated balloon angioplasty, plain old balloon angioplasty, percutaneous transluminal angioplasty, and stenting angioplasty were discussed regarding the outcomes with a focus on interest to prevent the stenosis.

Reck Suppresses Interleukin-17/Traf3ip2-Mediated Mmp-13 Activation And Human Aortic Smooth Muscle Cell Migration And Proliferation, Srinivas Mummidi, Nitin A. Das, Andrea J. Carpenter, Tadashi Yoshida, Manjunath Yariswamy, Ricardo Mostany, Reza Izadpanah, Yusuke Higashi, Sergiy Sukhanov, Makoto Noda, Ulrich Siebenlist, Randy S. Rector, Bysani Chandrasekar

School of Medicine Publications and Presentations

Sustained inflammation and matrix metalloproteinase (MMP) activation contribute to vascular occlusive/proliferative disorders. Interleukin-17 (IL-17) is a proinflammatory cytokine that signals mainly via TRAF3 Interacting Protein 2 (TRAF3IP2), an upstream regulator of various critical transcription factors, including AP-1 and NF-κB. Reversion inducing cysteine rich protein with kazal motifs (RECK) is a membrane-anchored MMP inhibitor. Here we investigated whether IL-17A/TRAF3IP2 signaling promotes MMP-13-dependent human aortic smooth muscle cell (SMC) proliferation and migration, and determined whether RECK overexpression blunts these responses. Indeed, IL-17A treatment induced (a) JNK, p38 MAPK, AP-1, NF-κB, and CREB activation, (b) miR-21 induction, (c) miR-27b and miR-320 inhibition, (d) …

Minocycline Inhibits Pdgf-Bb-Induced Human Aortic Smooth Muscle Cell Proliferation And Migration By Reversing Mir-221- And -222-Mediated Reck Suppression, Yusuke Higashi, Srinivas Mummidi, Sergiy Sukhanov, Tadashi Yoshida, Makoto Noda, Patrice Delafontaine, Bysani Chandrasekar

School of Medicine Publications and Presentations

Minocycline, a tetracycline antibiotic, is known to exert vasculoprotective effects independent of its anti-bacterial properties; however the underlying molecular mechanisms are not completely understood. Reversion Inducing Cysteine Rich Protein with Kazal Motifs (RECK) is a cell surface expressed, membrane anchored protein, and its overexpression inhibits cancer cell migration. We hypothesized that minocycline inhibits platelet-derived growth factor (PDGF)-induced human aortic smooth muscle cell (SMC) proliferation and migration via RECK upregulation. Our data show that the BB homodimer of recombinant PDGF (PDGF-BB) induced SMC migration and proliferation, effects significantly blunted by pre-treatment with minocycline. Further investigations revealed that PDGF-BB induced PI3K-dependent AKT …

Minocycline Inhibits Pdgf-Bb-Induced Human Aortic Smooth Muscle Cell Proliferation And Migration By Reversing Mir-221- And -222-Mediated Reck Suppression, Yusuke Higashi, Srinivas Mummidi, Sergiy Sukhanov, Tadashi Yoshida, Makoto Noda, Patrice Delafontaine, Bysani Chandrasekar

School of Medicine Publications and Presentations

Minocycline, a tetracycline antibiotic, is known to exert vasculoprotective effects independent of its anti-bacterial properties; however the underlying molecular mechanisms are not completely understood. Reversion Inducing Cysteine Rich Protein with Kazal Motifs (RECK) is a cell surface expressed, membrane anchored protein, and its overexpression inhibits cancer cell migration. We hypothesized that minocycline inhibits platelet-derived growth factor (PDGF)-induced human aortic smooth muscle cell (SMC) proliferation and migration via RECK upregulation. Our data show that the BB homodimer of recombinant PDGF (PDGF-BB) induced SMC migration and proliferation, effects significantly blunted by pre-treatment with minocycline. Further investigations revealed that PDGF-BB induced PI3K-dependent AKT …

Evaluating Wall Shear Stress Indices To Uncover Stimuli For Restenosis And Malapposition In Stented Coronary Arteries, Ali A. Aleiou

Master's Theses (2009 -)

The cause of coronary artery neointimal thickening leading to restenosis in ~10% of drug-eluting stents is unknown. Although research suggests adverse values of traditional wall shear stress (WSS) indices may contribute, studies to date have not accounted for stent geometry, which dictates local WSS patterns influencing drug concentration. Recently proposed WSS indices such as WSS variability and WSS exposure time (WSSET) may shed further light on restenosis or, the opposite effect, resorption. The objective of this investigation was to locally evaluate traditional and recently proposed post-stenting metrics and their respective impact on restenosis or resorption. This study used de-identified data …

Growing Impact Of Restenosis On The Surgical Treatment Of Peripheral Arterial Disease, Douglas W. Jones, Andres Schanzer, Yuanyuan Zhao, Todd A. Mackenzie, Brian W. Nolan, Michael S. Conte, Philip P. Goodney

Andres Schanzer

BACKGROUND: Patients with peripheral arterial disease often experience treatment failure from restenosis at the site of a prior peripheral endovascular intervention (PVI) or lower extremity bypass (LEB). The impact of these treatment failures on the utilization and outcomes of secondary interventions is poorly understood. METHODS AND RESULTS: In our regional vascular quality improvement collaborative, we compared 2350 patients undergoing primary infrainguinal LEB with 1154 patients undergoing secondary infrainguinal LEB (LEB performed after previous revascularization in the index limb) between 2003 and 2011. The proportion of patients undergoing secondary LEB increased by 72% during the study period (22% of all LEBs …

Effects Of Cpla-2 On The Migration And Proliferation Of Human Vascular Smooth Muscle Cells And The 2-D Migratory Patterns Of Tropomyosin In Femoral And Abdominal Aorta Tissue, Jaimeson Thomas Powell

Theses and Dissertations

Abstract 1: Platelet derived growth factor BB (PDGF BB) has an important influence on smooth muscle cell proliferation in restenosis and atherosclerosis. Our understanding of different signal transduction pathways involved in the response of smooth muscle cells to PDGF BB is potentially significant for understanding and manipulating these processes. Prior studies have demonstrated a crucial activation of cytosolic phospholipase A2 (cPLA2) in smooth muscle cells to PDGF BB with the production of arachidonic acid and prostaglandin E2. In these studies we investigated the role for another PLA2, calcium-independent PLA2 (iPLA2) in comparison to cPLA2 on smooth muscle cell migration and …

Smooth Muscle-Specific Expression Of Calcium-Independent Phospholipase A2 (Ipla2 ) Participates In The Initiation And Early Progression Of Vascular Inflammation And Neointima Formation, Shu Liu, Zhongwen Xie, Qingwei David Zhao, Huan Pang, John Turk, Lindsay E. Cormier, Wen Su, Guogang Zhao, Haifei Xu, Ming Gong, Zhenheng Guo

Biological Sciences Faculty and Staff Research

Background: The role of iPLA 2 β as a regulator of inflammatory signaling and neointima formation is unknown.

Result: Smooth muscle-specific expression of iPLA 2 β exacerbates proinflammatory cytokine production, macrophage infiltration, and neointima formation.

Conclusion: Smooth muscle-specific iPLA 2 β participates in the initiation and early progression of vascular inflammation and neointima formation.

Significance: iPLA 2 β may represent a novel therapeutic target for attenuating vascular inflammation and restenosis.

Coronary Artery Bypass Grafting After Percutaneous Coronary Intervention, Syed Shahabuddin, Syed Ahmed Sami, Junaid Alam Ansari, Shazia Perveen, Shumaila Furnaz, Saulat H. Fatimi, Hasanat Sharif

Section of Cardiothoracic Surgery

Following percutaneous intervention (PCI), restenosis, progression of disease and multi-vessel involvement may require further intervention in the form of surgical revascularization. Patients with coronary artery bypass grafting (CABG) done after PCI were evaluated to find out the reason for the need of surgical revascularization. Over a period of 12 months, 610 patients underwent CABG. Out of them, 34 patients had previous PCI/stenting. Coronary risk factors including hypertension in 85%, diabetes mellitus in 60%, dyslipidemia in 60%, tobacco use in 50% and a positive family history was present in 53% of the patients. All patients were symptomatic. Multi-vessel disease was present …

Effects Of Arterial Strain And Stress In The Prediction Of Restenosis Risk: Computer Modeling Of Stent Trials, Shijia Zhao, Linxia Gu, Stacey R. Froemming

Department of Mechanical and Materials Engineering: Faculty Publications

Purpose — In-stenting restenosis is one of the major complications after stenting. Clinical trials of various stent designs have reported different restenosis rates. However, quantitative correlation between stent features and restenosis statistics is scant. In this work, it is hypothesized that stress concentrations on arterial wall caused artery injury, which initiates restenosis. The goal is to assess the correlation between stent-induced arterial stress and strain and the documented restenosis rates.

Methods — Six commercially available stents, including balloon-expandable stents and self-expanding stents, were virtually implanted into the arteries through finite element method. The resulted peak Von Mises stress, principal stress, …

We Can Do It Together: Par1/Par2 Heterodimer Signaling In Vsmcs., Rafal Pawlinski, Michael Holinstat

Department of Medicine Faculty Papers

In this issue, Sevigny and colleagues demonstrate that a protease-activated receptor 1 (PAR1)-PAR2 heterodimer regulates vascular smooth muscle cell (VSMC) hyperplasia following vascular injury ¹. PARs belong to a family of G-protein coupled receptors that are proteolytically activated by a variety of proteases ^{2, 3}. Cleavage of PARs results in intracellular signaling mediated by activation of various G proteins including G_12/13, G_q, and G_i ^{2, 4-6}. The PAR family consists of 4 members, PAR1-PAR4, with PARs 1, 3, and 4 being primarily activated by thrombin, while PAR2 is activated by trypsin and …

Non-Viral Enos Gene Delivery And Transfection With Stents For The Treatment Of Restenosis, Luis A. Brito, Saradha Chandrasekhar, Steven R. Little, Mansoor M. Amiji

Mansoor M. Amiji

Background In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model. Methods Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation. Results The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR …