Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis.

The cellular and molecular processes that control vascular injury responses after percutaneous coronary intervention involve a complex interplay among vascular cells and progenitor cells that control arterial remodeling, neointimal proliferation, and re-endothelialization. Drug-eluting stents (DES) improve the efficacy of percutaneous coronary intervention by modulating vascular inflammation and preventing neointimal proliferation and restenosis. Although positive effects of DES reduce inflammation and restenosis, negative effects delay re-endothelialization and impair endothelial function. Delayed re-endothelialization and impaired endothelial function are linked to stent thrombosis and adverse clinical outcomes after DES use. Compared with bare-metal stents, DES also differentially modulate mobilization, homing, and differentiation of vascular progenitor cells involved in re-endothelialization and neointimal proliferation. The effects of DES on vascular inflammation and repair directly impact clinical outcomes with these devices and dictate requirements for extended-duration dual antiplatelet therapy.

[1]  S. Rafii,et al.  Recruitment of Stem and Progenitor Cells from the Bone Marrow Niche Requires MMP-9 Mediated Release of Kit-Ligand , 2002, Cell.

[2]  Michael Joner,et al.  Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. , 2006, Journal of the American College of Cardiology.

[3]  V. Bhatia,et al.  Drug-eluting stents: new era and new concerns , 2004, Postgraduate Medical Journal.

[4]  Marco Valgimigli,et al.  The unrestricted use of paclitaxel- versus sirolimus-eluting stents for coronary artery disease in an unselected population: one-year results of the Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registry. , 2005, Journal of the American College of Cardiology.

[5]  Dong Bin Kim,et al.  Drug-eluting stent implantation could be associated with long-term coronary endothelial dysfunction. , 2007, International heart journal.

[6]  T. Murohara,et al.  Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. , 2000, The Journal of clinical investigation.

[7]  R. Virmani,et al.  Comparison of Inflammatory Response After Implantation of Sirolimus- and Paclitaxel-Eluting Stents in Porcine Coronary Arteries , 2009, Circulation.

[8]  K. Maekawa,et al.  Severe Endothelial Dysfunction After Sirolimus-Eluting Stent Implantation , 2006 .

[9]  N. Krott,et al.  A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells. , 2006, Journal of the American College of Cardiology.

[10]  Hyun-Jai Cho,et al.  Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial , 2004, The Lancet.

[11]  Xing Chen,et al.  Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration. , 2005, American journal of physiology. Cell physiology.

[12]  M. Buerke,et al.  Rapamycin reduces neointima formation during vascular injury. , 2003, VASA. Zeitschrift fur Gefasskrankheiten.

[13]  P. E. Van den Steen,et al.  Neutrophil Gelatinase B and Chemokines in Leukocytosis and Stem Cell Mobilization , 2002, Leukemia & lymphoma.

[14]  E. Edelman,et al.  Coated stents: local pharmacology. , 1998, Seminars in interventional cardiology : SIIC.

[15]  S. Fukuda,et al.  Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GROβ/CXCL2 and GROβT /CXCL2Δ4 , 2004 .

[16]  J. Isner,et al.  Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia , 2001, Circulation.

[17]  R. Nagai,et al.  Potent Inhibitory Effect of Sirolimus on Circulating Vascular Progenitor Cells , 2005, Circulation.

[18]  Giuseppe Musumeci,et al.  Localized Hypersensitivity and Late Coronary Thrombosis Secondary to a Sirolimus-Eluting Stent: Should We Be Cautious? , 2004, Circulation.

[19]  Deepak L. Bhatt,et al.  What is the risk of stent thrombosis associated with the use of paclitaxel-eluting stents for percutaneous coronary intervention?: a meta-analysis. , 2005, Journal of the American College of Cardiology.

[20]  D. Simon,et al.  Molecular Basis of Restenosis and Drug-Eluting Stents , 2005, Circulation.

[21]  K. Node,et al.  Mobilization of CD34-Positive Bone Marrow–Derived Cells After Coronary Stent Implantation: Impact on Restenosis , 2007, Circulation.

[22]  P. Libby,et al.  Sustained Activation of Vascular Cells and Leukocytes in the Rabbit Aorta After Balloon Injury , 1993, Circulation.

[23]  M. Schwaiger,et al.  Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. , 2006, JAMA.

[24]  Fernando Alfonso,et al.  Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies. , 2005, Journal of the American College of Cardiology.

[25]  F. Welt,et al.  Inflammation and Restenosis in the Stent Era , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[26]  L. McIntire,et al.  Platelet Glycoprotein Ibα Is a Counterreceptor for the Leukocyte Integrin Mac-1 (Cd11b/Cd18) , 2000, The Journal of experimental medicine.

[27]  J. Folkman.  Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[28]  W. Edwards,et al.  Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Serruys,et al.  Post–Sirolimus-Eluting Stent Restenosis Treated With Repeat Percutaneous Intervention: Late Angiographic and Clinical Outcomes , 2004, Circulation.

[30]  G. Patti,et al.  Percutaneous coronary intervention utilizing a new endothelial progenitor cells antibody‐coated stent: A prospective single‐center registry in high‐risk patients , 2008, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[31]  Seiki Nagata,et al.  Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. , 2006, Journal of the American College of Cardiology.

[32]  M. Makuuchi,et al.  Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis , 2002, Nature Medicine.

[33]  W. Hofmann,et al.  HMG-CoA Reductase Inhibitors Reduce Senescence and Increase Proliferation of Endothelial Progenitor Cells via Regulation of Cell Cycle Regulatory Genes , 2003, Circulation research.

[34]  D. Celermajer,et al.  Endothelial dysfunction and restenosis following percutaneous coronary intervention. , 2007, International journal of cardiology.

[35]  T. Springer,et al.  Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. , 1996, Blood.

[36]  T. Miyazaki,et al.  Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris. , 2000, The American journal of cardiology.

[37]  P. Serruys,et al.  Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation. , 2006, European heart journal.

[38]  M. Noshiro,et al.  OE-277 DEC1, a Member of the Fifth Clock-Gene Family, is Induced by Angiotensin II, Growth Factors, and Hypoxia in Vascular Cells(Hypertension, basic-1, The 71st Annual Scientific Meeting of the Japanese Circulation Society) , 2007 .

[39]  A. Wagstaff,et al.  The Paclitaxel (TAXUS™)-Eluting Stent , 2004 .

[40]  A. Schober,et al.  Peripheral CD34+ cells and the risk of in-stent restenosis in patients with coronary heart disease. , 2005, The American journal of cardiology.

[41]  A. Schober,et al.  Crucial Role of Stromal Cell–Derived Factor-1&agr; in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice , 2003, Circulation.

[42]  T. Inoue,et al.  Lower expression of neutrophil adhesion molecule indicates less vessel wall injury and might explain lower restenosis rate after cutting balloon angioplasty. , 1998, Circulation.

[43]  Michael Joner,et al.  Vascular Responses to Drug Eluting Stents: Importance of Delayed Healing , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[44]  E. Edelman,et al.  Neutrophil, Not Macrophage, Infiltration Precedes Neointimal Thickening in Balloon-Injured Arteries , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[45]  S. Maśliński,et al.  Ligation of selectin L and integrin CD11b/CD18 (Mac-1) induces release of gelatinase B (MMP-9) from human neutrophils , 1998, Inflammation Research.

[46]  Y. S. Kim,et al.  Sirolimus inhibits platelet-derived growth factor-induced collagen synthesis in rat vascular smooth muscle cells. , 2005, Transplantation proceedings.

[47]  E. Edelman,et al.  Decreased neointimal formation in Mac-1(-/-) mice reveals a role for inflammation in vascular repair after angioplasty. , 2000, The Journal of clinical investigation.

[48]  J. Ormiston,et al.  Drug-eluting stents and late stent thrombosis , 2007, The Lancet.

[49]  B. Tesfamariam.  Drug Release Kinetics From Stent Device-Based Delivery Systems , 2008, Journal of cardiovascular pharmacology.

[50]  Simon Wandel,et al.  Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis , 2007, The Lancet.

[51]  Y. Yoon,et al.  Local Gene Transfer of phVEGF-2 Plasmid by Gene-Eluting Stents: An Alternative Strategy for Inhibition of Restenosis , 2004, Circulation.

[52]  R. Cummings,et al.  Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. , 1997, The Journal of clinical investigation.

[53]  K. Seung,et al.  Long-term coronary endothelial function after zotarolimus-eluting stent implantation. A 9 month comparison between zotarolimus-eluting and sirolimus-eluting stents. , 2008, International heart journal.

[54]  O. Hess,et al.  Sirolimus-eluting stents associated with paradoxic coronary vasoconstriction. , 2005, Journal of the American College of Cardiology.

[55]  T. Murohara,et al.  Mobilization of Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction , 2001, Circulation.

[56]  T. Inoue,et al.  Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty. , 1996, Journal of the American College of Cardiology.

[57]  A. Uitterlinden,et al.  Analysis of VNTR loci amplified by the polymerase chain reaction for investigating the origin of intimal smooth muscle cells in a coronary artery lesion developing after heart transplantation in man. , 1993, American heart journal.

[58]  Matthew H Samore,et al.  Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. , 2006, Journal of the American College of Cardiology.

[59]  D. Wagner,et al.  PADGEM protein: A receptor that mediates the interaction of activated platelets with neutrophils and monocytes , 1989, Cell.

[60]  T. Akasaka,et al.  Sirolimus accelerates senescence of endothelial progenitor cells through telomerase inactivation. , 2006, Atherosclerosis.

[61]  J. Barry,et al.  The Taxus drug-eluting stent: a new paradigm in controlled drug delivery. , 2006, Advanced drug delivery reviews.

[62]  D. Murdoch,et al.  The Sirolimus-Eluting Stent , 2022, Reactions Weekly.

[63]  C. Cerletti,et al.  Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the beta 2 integrin CD11b/CD18. , 1996, Blood.

[64]  R. Virmani,et al.  Pathological Correlates of Late Drug-Eluting Stent Thrombosis: Strut Coverage as a Marker of Endothelialization , 2007, Circulation.

[65]  J. Roelandt,et al.  Images in Cardiovascular Medicine , 2000 .

[66]  Fesc,et al.  Safety of Coronary Sirolimus-Eluting Stents in Daily Clinical Practice: One-Year Follow-Up of the e-Cypher Registry , 2006, Circulation.

[67]  P. Libby,et al.  Intertwining of thrombosis and inflammation in atherosclerosis , 2007, Current opinion in hematology.

[68]  P. Serruys,et al.  Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients. , 2011, Atherosclerosis.

[69]  B. Brott,et al.  Stainless Steel Ions Stimulate Increased Thrombospondin-1-Dependent TGF-Beta Activation by Vascular Smooth Muscle Cells: Implications for In-Stent Restenosis , 2009, Journal of Vascular Research.

[70]  P. Serruys,et al.  Abstract 5998: Final Results of the HEALING 2B Trial to Evaluate a Bioengineered CD34 Antibody Coated Stent (GenousTMStent) Designed to Promote Vascular Healing by Capture of Circulating Endothelial Progenitor Cells in CAD Patients , 2008 .

[71]  R. Jaffe,et al.  Late and very late thrombosis of drug-eluting stents: evolving concepts and perspectives. , 2007, Journal of the American College of Cardiology.

[72]  K. Maekawa,et al.  Impaired endothelial vasomotor function after sirolimus-eluting stent implantation. , 2007, Circulation journal : official journal of the Japanese Circulation Society.

[73]  C. Rogers.  A monoclonal antibody to the b2-leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits , 1998 .

[74]  Patrick W Serruys,et al.  Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy , 2004, The Lancet.

[75]  David O. Williams,et al.  Outcomes of 6906 Patients Undergoing Percutaneous Coronary Intervention in the Era of Drug-Eluting Stents: Report of the DEScover Registry , 2006, Circulation.

[76]  P. Serruys,et al.  Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. , 2005, Journal of the American College of Cardiology.

[77]  Christina K. Chan,et al.  Sirolimus blocks the accumulation of hyaluronan (HA) by arterial smooth muscle cells and reduces monocyte adhesion to the ECM. , 2007, Atherosclerosis.

[78]  T. Edgington,et al.  Two independent sets of monoclonal antibodies define neoepitopes linked to soluble ligand binding and leukocyte adhesion functions of activated alpha M beta 2. , 1994, Circulation research.

[79]  M. Joner,et al.  Polymer coatings and delayed arterial healing following drug-eluting stent implantation. , 2009, Minerva cardioangiologica.

[80]  U. Laufs,et al.  The PPAR-γ agonist pioglitazone increases neoangiogenesis and prevents apoptosis of endothelial progenitor cells , 2007 .

[81]  Aloke V. Finn,et al.  Delayed Arterial Healing and Increased Late Stent Thrombosis at Culprit Sites After Drug-Eluting Stent Placement for Acute Myocardial Infarction Patients: An Autopsy Study , 2008, Circulation.

[82]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[83]  Deepak L. Bhatt,et al.  Risk of thrombosis with the use of sirolimus-eluting stents for percutaneous coronary intervention (from registry and clinical trial data). , 2005, The American journal of cardiology.

[84]  L. Mauri,et al.  The conundrum of late and very late stent thrombosis following drug-eluting stent implantation , 2007, Current opinion in cardiology.

[85]  P. Serruys,et al.  Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. , 2005, Journal of the American College of Cardiology.

[86]  P. Serruys,et al.  Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions , 2007, Circulation.

[87]  E. Edelman,et al.  A mAb to the beta2-leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[88]  E. Kim,et al.  Six-month comparison of coronary endothelial dysfunction associated with sirolimus-eluting stent versus Paclitaxel-eluting stent. , 2008, JACC. Cardiovascular interventions.

[89]  W. Wijns,et al.  Differential effects of drug-eluting stents on local endothelium-dependent coronary vasomotion. , 2008, Journal of the American College of Cardiology.

[90]  R. Cummings,et al.  Role of PSGL-1 binding to selectins in leukocyte recruitment. , 1997, The Journal of clinical investigation.

[91]  R. Virmani,et al.  Differential Response of Delayed Healing and Persistent Inflammation at Sites of Overlapping Sirolimus- or Paclitaxel-Eluting Stents , 2005, Circulation.

[92]  Y. Sakai,et al.  Stent-Induced Expression and Activation of the Leukocyte Integrin Mac-1 Is Associated With Neointimal Thickening and Restenosis , 2003, Circulation.

[93]  S. Fichtlscherer,et al.  Increase in Circulating Endothelial Progenitor Cells by Statin Therapy in Patients With Stable Coronary Artery Disease , 2001, Circulation.