[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. These life-threatening disorders are a major cause of emergency medical care and hospitalizations in the United States. In 1996, the National Center for Health Statistics reported 1 433 000 hospitalizations for UA or NSTEMI. In recognition of the importance of the management of this common entity and of the rapid advances in the management of this condition, the need to revise guidelines published by the Agency for Health Care Policy and Research (AHCPR) and the National Heart, Lung and Blood Institute in 1994 was evident. This Task Force therefore formed the current committee to develop guidelines for the management of UA and NSTEMI. The present guidelines supersede the 1994 guidelines.

The customary ACC/AHA classifications I, II, and III summarize both the evidence and expert opinion and provide final recommendations for both patient evaluation and therapy:

Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective .

Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. 

Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy. 

Class IIb: Usefulness/efficacy is less well established by evidence/opinion. 

Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful. 

The weight of the evidence was ranked highest (A) if the data …

/pdf/acc-aha-guidelines-for-the-management-of-patients-with-4ru5c6nutz.pdf

ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Executive summary and recommendations: A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on the management of patients with unstable angina)

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

/pdf/meta-analysis-of-74-046-individuals-identifies-11-new-406eax0kye.pdf

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models. Hypoxia has been shown to be a major inducer of VEGF gene transcription. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGF receptors. The role of VEGF in developmental angiogenesis is emphasized by the finding that loss of a single VEGF allele results in defective vascularization and early embryonic lethality. VEGF is critical also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. In situ hybridization studies demonstrate expression of VEGF mRNA in the majority of human tumors. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with various VEGF inhibitors in a variety of malignancies are ongoing. Very recently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.

/pdf/vascular-endothelial-growth-factor-basic-science-and-17gyy6h97s.pdf

Vascular endothelial growth factor: basic science and clinical progress.

The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

/pdf/integrins-in-cancer-biological-implications-and-therapeutic-2ejzg8fop4.pdf

Integrins in cancer: biological implications and therapeutic opportunities

Oxidative stress in angiogenesis and vascular disease.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(98)11086-3.pdf

Platelet GPIIb-IIIa blockers

A Mechanism for Modulation of Cellular Responses to VEGF: Activation of the Integrins

Dyslipidemia is associated with a prothrombotic phenotype; however, the mechanisms responsible for enhanced platelet reactivity remain unclear. Proatherosclerotic lipid abnormalities are associated with both enhanced oxidant stress and the generation of biologically active oxidized lipids, including potential ligands for the scavenger receptor CD36, a major platelet glycoprotein. Using multiple mouse in vivo thrombosis models, we now demonstrate that genetic deletion of Cd36 protects mice from hyperlipidemia-associated enhanced platelet reactivity and the accompanying prothrombotic phenotype. Structurally defined oxidized choline glycerophospholipids that serve as high-affinity ligands for CD36 were at markedly increased levels in the plasma of hyperlipidemic mice and in the plasma of humans with low HDL levels, were able to bind platelets via CD36 and, at pathophysiological levels, promoted platelet activation via CD36. Thus, interactions of platelet CD36 with specific endogenous oxidized lipids play a crucial role in the well-known clinical associations between dyslipidemia, oxidant stress and a prothrombotic phenotype.

/pdf/platelet-cd36-links-hyperlipidemia-oxidant-stress-and-a-1ju919vsgn.pdf

Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype

Akt kinases control essential cellular functions, including proliferation, apoptosis, metabolism and transcription, and have been proposed as promising targets for treatment of angiogenesis-dependent pathologies, such as cancer and ischemic injury. But their precise roles in neovascularization remain elusive. Here we show that Akt1 is the predominant isoform in vascular cells and describe the unexpected consequences of Akt1 knockout on vascular integrity and pathological angiogenesis. Angiogenic responses in three distinct in vivo models were enhanced in Akt1−/− mice; these enhanced responses were associated with impairment of blood vessel maturation and increased vascular permeability. Although impaired vascular maturation in Akt1−/− mice may be attributed to reduced activation of endothelial nitric oxide synthase (eNOS), the major phenotypic changes in vascular permeability and angiogenesis were linked to reduced expression of two endogenous vascular regulators, thrombospondins 1 (TSP-1) and 2 (TSP-2). Re-expression of TSP-1 and TSP-2 in mice transplanted with wild-type bone marrow corrected the angiogenic abnormalities in Akt1−/− mice. These findings establish a crucial role of an Akt-thrombospondin axis in angiogenesis.

/pdf/akt1-regulates-pathological-angiogenesis-vascular-maturation-3i9lfisgov.pdf

Tatiana V. Byzova

Papers

Oxidative stress in angiogenesis and vascular disease.

Platelet GPIIb-IIIa blockers

A Mechanism for Modulation of Cellular Responses to VEGF: Activation of the Integrins

Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype

Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo