Much currently known information about vulnerable plaque stems from postmortem studies that identified several characteristics making them prone to rupture, including the presence of a thin fibrous cap and a large lipid core. This study used optical coherence tomography (OCT) to assess culprit and remote coronary narrowings and investigate whether intracoronary OCT in living patients was able to visualize morphologic features associated with vulnerable plaque in postmortem studies. Twenty-three patients successfully underwent OCT before percutaneous coronary intervention. The culprit lesion and mild to moderate coronary narrowings remote from the target stenosis were investigated. Using OCT, the culprit lesion was found to be fibrous in 39.1%, fibrocalcific in 34.4%, and lipid rich in 26.1% of cases. Two patients met criteria for thin-cap fibroatheroma (TCFA; defined as the presence of a signal-rich fibrous cap covering a signal-poor lipid/necrotic core with cap thickness <0.2 mm). Most plaques at remote segments were proximal to the culprit lesion (73.9%) and predominantly fibrous and lipid rich. OCT identified 7 TCFA lesions in 6 patients with a mean cap thickness of 0.19 ± 0.05 mm, extending for 103° ± 49° of the total vessel circumference. At 24 months of clinical follow-up, the only event occurred in a patient with in-stent restenosis who underwent repeated percutaneous revascularization. There were no clinically apparent plaque rupture–related events in the 6 patients found to have remote TCFA. This study showed that OCT can be safely applied to image beyond the culprit lesion and can detect in vivo morphologic features associated with plaque vulnerability using retrospective pathologic examination. In conclusion, detection of TCFA, particularly in stable patients, is desirable and may principally allow for early intervention and prevention of adverse events.
This inaugural issue of Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation (JCOPDF) honors the 10th anniversary of the formation of the COPD Foundation.1 It is also a landmark beginning of the next decade – a symbol of bringing the worldwide COPD community together to find
Paper presented at the sixth International Conference on the Environmental and Technical Implications of Construction with Alternative Materials (WASCON 2006), held 30 May-2 June 2006, Belgrade, Serbia.
The impact of reduced left ventricular ejection fraction (LVEF) on very long-term prognosis following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) has been debated. The aim of this study was to investigate the impact of LVEF at baseline on 10-year mortality in the SYNTAX trial.Patients (n = 1800) were categorized into three sub-groups: reduced (rEF ≤ 40 %), mildly reduced (mrEF 41-49 %), and preserved LVEF (pEF ≥ 50 %). The SYNTAX score 2020 (SS-2020) was applied in patients with LVEF<50 % and ≥ 50 %.Ten-year mortalities were 44.0 %, 31.8 %, and 22.6 % (P < 0.001) in patients with rEF (n = 168), mrEF (n = 179), and pEF (n = 1453). Although no significant differences were observed, the mortality with PCI was higher than with CABG in patients with rEF (52.9 % vs 39.6 %, P = 0.054) and mrEF (36.0 % vs. 28.6 %, P = 0.273), and comparable in pEF (23.9 % vs. 22.2 %, P = 0.275). Calibration and discrimination of the SS-2020 in patients with LVEF<50 % were poor, whilst they were reasonable in those with LVEF≥50 %. The proportion of patients eligible for PCI who had a predicted equipoise in mortality with CABG was estimated to be 57.5 % in patients with LVEF≥50 %. CABG was safer than PCI in 62.2 % of patients with LVEF<50 %.Reduced LVEF was associated with an increased risk of 10-year mortality in patients revascularized either surgically or percutaneously. Compared to PCI, CABG was safe revascularization in patients with LVEF≤40 %. In patients with LVEF≥50 % individualized 10-year all-cause mortality predicted by SS-2020 was helpful in decision-making whilst the predictivity in patients with LVEF<50 % was poor.
Novel Approaches to Cardiac Regeneration - The (Pre-Clinical) Reality of Myoblast Transplantation, D.A. Taylor and E.J. von den Bos Cellular Cardiomyoplasty: The Biology and Clinical Importance of Milieu-Dependent Differentiation, R.C.J. Chiu and J.-S. Wang Transplantation of Endothelial Progenitor Cells for Therapeutic Neovascularization, A. Kawamoto, D.W. Lsordo, and T. Asahara Embryonic Stem Cell Approaches to Induce Myogenesis: Preliminary Experimental Findings, L. Yankelson, I. Kehat, and L. Gepstein Long-Term Effects of Fetal and Neonatal Cardiac Myocyte Transplantation on the Infarcted Heart, R.A. Kloner, J. Muller-Ehmsen, M. Yao, J. Leor, T. Refflemann, S. Etzion, S. Hale, J. Dow, B. Simkovich, K.L. Peterson, and L. Kedes The Role of Cardiac Fibroblasts in Cardiac Regeneration, M. Eghbali-Webb Transplantation of Satellite Cells for Myocardial Regeneration, R.L. Kao Myogenic Cardiac Fibroblasts for Myocardial Infarction Strategies to Enhance the Efficacy of Myoblast Transplantation to the Heart, R.L. Kao, J.J. Laffan, T.K. Chin, D.G. Pennington, and C.E. Ganote Stem Cells and Myocardial Regeneration, E.M. Molnar Angiogenic Effect of Endothelial Precursor Cells: Implications for Development of Cell Therapy Protocols for Myocardial Infarction. S. Itescu, A.A. Kocher, and M.D. Schuster Cell Transplantation for Therapeutic Angiogenesis, P.W.M. Fedak, H. Zhang, and R.-K. Li Transplantation of Autologous Endothelial Cells to Induce Neovascularization: Experimental Findings, V. Chekanov, V. Nikolaychik, M. Tsapenko, and N.K. Kipshidze Intramyocardial Delivery of Autologous Bone Marrow: Experimental Justification and Early Clinical Experiences, S. Fuchs, T. Kinnaird, and E. Stabile Long-Term Clinical Results of Cellular Cardiomyoplasty by Autologous Skeletal Myoblasts, P. Menasche Challenges of Myogenesis and Repair of the Heart, P.W. Serruys, P.C. Smits, W. van der Giessen, H.B. Haines, J.M. Harvey, and J.L. Green Myoblast Genome Therapy and the Regenerative Heart, P.K. Law, E.K.W. Sim, H.Kh, Haider, G. Fang, F. Chua, T. Kakuchaya, V.S. Repin, and L.A. Bockeria Transplantation of Autologous Mononuclear Bone Morrow Cells: Clinical Results and Perspectives, M. Brehm, T. Zeus, and B.E. Strauer Therapeutic Angiogenesis for Cardiac and Peripheral Vascular Disease by Autologous Bone Marrow Cell Transplantation, H. Matsubara Bone Marrow and Bone Marrow-Derived Mononuclear Stem Cell Therapy for the Chronically Ischemic Myocardium, R. Waksman and R. Baffour Cell Transplantation: First US Clinical Experience, M.S. Penn and P.M. McCarthy Adipose Stromal Cell Therapy for Cardiovascular Disease, J. Rehman and K.L. March Intramyocardial Gene and Cellular Delivery for Myocardial Angiogenesis and Regeneration, R. Kornowski The Vast Potential of the Coronary Venous System for Drug and Biologic Interventions, M. Redzaee, E.T. Price, P.J. Fitzgerald, P.G. Yock, and A.C. Yeung Transvenous Intramyocardial Injection, P.C. Smits, W.J. van der Giessen, C.A. Thompson, and P.W. Serruys Perivascular Endothelial Cell Tissue Engineering, H.M. Nugent and E.R. Edelman Tissue-Engineered Small Vessel Grafts, B.D. MacNeill and S.N. Oesterle The Living Stent: Cell-Based Implantable Vascular Therapy, R.S. Schwartz and K. Miyauchi Endoluminal Transplantation of Endothelial Cells, N. Kipshidze, M.H. Keelan, M.Tsapenko, M.B. Leon, C. Haudenschild, and J. Moses
Balloon angioplasty achieves luminal enlargement by fracturing the atherosclerotic intima at its point of least resistance, thereby creating a dissection plane and space with dehiscence of the intima from the media. This barotraumatic dissection triggers an inflammatory and proliferative reaction, resulting in a restenosis process at medium-term. In the era of plain old balloon angioplasty, quantitative angiographic studies at follow-up demonstrated that - the greater the acute luminal gain was after balloon angioplasty, the greater the late luminal loss was at follow-up. The interventional cardiologists coined the following motto “the more you gain, the more you lose”. However, in the current era of drug coated balloon (DCB), it appears that this vexing conundrum could have been abrogated. A recently published DCB study in small de novo vessel has demonstrated that there was a slightly negative correlation between the volume of dissection assessed by optical coherence tomography and the angiographic late luminal loss (now gain) after Paclitaxel coated balloon treatment. In other words, the barotraumatic dissection does not necessarily herald a restenosis process in the era of DCB. This article revisits the mechanism of balloon angioplasty and explores how DCB with Paclitaxel may change the paradigm of balloon angioplasty as default treatment in CAD percutaneous treatment.
Beta 2-adrenoreceptor agonists and glucocorticosteroids are the two most effective treatments for asthma and are often used in combination. Glucocorticoids mediate their anti-inflammatory effects through the action of activated glucocorticoid receptors (GRs). Many of the effects of GRs on the synthesis of cytokines and other inflammatory mediators are due to a direct interaction with other deoxyribonucleic acid (DNA)-binding proteins belonging to the basic leucine zipper (bZIP) group of transcription factors, such as activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). Beta 2-agonists are potent bronchodilators at low doses and at high doses can activate gene transcription via a bZIP protein, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB). Activated GRs and CREB can interact with each other within the nucleus to modulate both DNA-binding and gene transcription in either a positive or inhibitory manner, depending on cell type. In lung cells, high doses of beta 2-agonists reduce the ability of GR to bind DNA, a process which is mediated by CREB activation. Inhibition of GR DNA-binding by CREB raises the possibility that high-dose beta 2-agonists could have functional antiglucocorticoid activity and may be a basis for the reported increase in asthma morbidity and mortality in industrialized countries, which have increasing per capita beta 2-agonist use.
<b>Background</b> Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, associated with accelerated lung aging. Immune cells in aging diseases display features of senescence (immunosenescence) and chronic inflammation (inflammaging). COPD macrophages are more pro-inflammatory and have defective phagocytic function, but features of senescence in COPD macrophages is not well studied. <b>Aim</b> To examine expression of senescence markers in macrophages from healthy and COPD subjects, in the presence and absence of oxidative stress (H<sub>2</sub>O<sub>2</sub>). <b>Methods</b> Peripheral blood monocytes were isolated from age-matched non-smokers (NS) (n=9) and COPD patients (n=12) and then cultured in GM-CSF for 12 days to generate monocyte-derived macrophages (MDM). MDM were then treated with ±200µM H<sub>2</sub>O<sub>2</sub> for 48h and expression of senescence markers was measured using qPCR. <b>Results</b> At baseline, COPD MDM have increased expression of senescence markers p21CIP1 (2-fold, p>0.05), p27 (2.6-fold, p<0.05) and reduced anti-aging molecule, sirtuin (SIRT)6 (49%, p<0.05) and increased expression of senescence associated secretory phenotype (SASP) factors interleukin (IL)6 (50-fold, p<0.05) and CXCL8 (127-fold, p<0.01), compared to age-matched MDM from NS. In the presence of oxidative stress (H<sub>2</sub>O<sub>2</sub>), COPD MDM have further increased expression of p21CIP1 (2-fold, p<0.05), p27 (25%, p>0.05), IL6 (8-fold, p<0.05), CXCL8 (10-fold, p<0.01) and reduced SIRT1 (23%, p>0.05) and SIRT6 (61%, p<0.05), compared to age-matched NS. <b>Conclusion</b> COPD MDM have elevated expression of senescence and SASP markers compared to healthy MDM and are more susceptible to oxidative stress induced senescence. This maybe associated with the altered macrophage phenotype in COPD.
