"It is quite useless to argue the questions concerning the development of intimal scleroses if we study and discuss the late stages of the disease alone. If we wish to gain insight into the complex ...question of arterio-sclerosis we must attempt to follow the lesion from its earliest beginning" (Klotz and Manning, J Path Bact 1911: 16; 211-20). Over thirty years ago Boneu and colleagues published a report of raised levels of plasma von Willebrand factor (vWf) in patients with arteritis, diabetes and sepsis. They concluded that raised levels of this molecule indicate endothelial damage, and may possibly be a contributory factor in thrombosis in arterial disease. The former aspect of this conclusion is now accepted, and numerous studies on the risk factors for atherosclerosis provide mechanisms for this damage. Other studies have demonstrated raised levels in cancer and in connective tissue disease. Numerous long-term follow-up studies have also demonstrated that increased vWf predicts major cardiovascular end points. However, the link between these studies, and the latter aspect of Boneu's conclusion, that raised vWf contributes to thrombosis is, although attractive, nevertheless unproven. Despite this, vWf remains the most important plasma marker of endothelial damage/dysfunction and as such attracts clinical attention.
Abstract A bidirectional relationship exists between atrial fibrillation (AF) and chronic renal disease. Patients with AF have a higher incidence of renal dysfunction, and the latter predisposes to ...incident AF. The coexistence of both conditions results in a higher risk for thromboembolic-related adverse events but a paradoxical increased hemorrhagic risk. Oral anticoagulants (both vitamin K antagonists VKAs and non-VKA oral anticoagulants NOACs) have been demonstrated to be effective in mild to moderate renal dysfunction. Patients with severe renal impairment were excluded from the non-VKA oral anticoagulant trials, so limited data are available. In end-stage renal failure, the net clinical benefit of VKAs in dialysis-dependent patients remains uncertain, although some evidence suggests that such patients may do well with high-quality anticoagulation control. Risk stratification and careful follow-up of such patients are necessary to ensure a net clinical benefit from thromboprophylaxis.
Because they are neither new nor novel these days, these agents are called target-specific oral anticoagulants, direct oral anticoagulants, and non-vitamin K oral anticoagulants (NOACs) (1,2). ......methods are widely agreed upon, each user must decide which is most appropriate in their own setting.
The adhesion molecule P-selectin (CD62P) is of interest because of its role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble ...form as a plasma predictor of adverse cardiovascular events. Although present on the external cell surface of both activated endothelium and activated platelets, it now seems clear that most, if not all, of the measured plasma P-selectin is of platelet origin. P-selectin is partially responsible for the adhesion of certain leukocytes and platelets to the endothelium. Animal models have also shown the important role of P-selectin in the process of atherogenesis. For example, increased P-selectin expression has been demonstrated on active atherosclerotic plaques; in contrast, fibrotic inactive plaques lack P-selectin expression, and animals lacking P-selectin have a decreased tendency to form atherosclerotic plaques. Increased levels of soluble P-selectin in the plasma have also been demonstrated in a variety of cardiovascular disorders, including coronary artery disease, hypertension and atrial fibrillation, with some relationship to prognosis. The objective of this review is to provide an overview of the current literature on this molecule and thus present a concise view of its potential in dissecting the pathophysiology of atherosclerosis. In doing so we shall focus primarily on human biology but will note a small number of excellent lessons provided by non-human work.
...the endothelium is of great interest to oncologists, cardiologists and haematologists, all of whom are keen to develop methods of assessing the integrity of this tissue. ...armed, increased ...numbers of CECs were described in many cardiovascular, inflammatory and neoplastic diseases, the interpretation being that each disease process was (at least) partly responsible for this increase 14–16. ...the process of treating the risk factors for atherosclerosis, whether by formal pharmaceutical intervention (statins, ACE inhibitors and hypoglycaemics) or by simply adopting a healthy lifestyle (no smoking, a diet rich in fresh fruit and vegetables, regular exercise, avoidance of overweight and obesity), has been known for decades as effective in reducing major cardiovascular events 31,32. Marker Antigen name Expression on non-endothelial cells PECAM-1 CD31 Platelets and leucocytes ICAM-1 CD54 Leucocytes Endoglin CD105 Macrophages, activated monocytes, erythroid progenitors and pre-B lymphocytes VCAM-1 CD106 Stromal cells, smooth muscle cells and fibroblasts Thrombomodulin CD141 Platelets, monocytes, neutrophils and keratinocytes E-cadherin CD144 Foetal liver cells P1H12, S-endo-1 CD146 Pericytes, bone marrow fibroblasts, nerve fibres, activated T-lymphocyte and malignant cells VEGF receptor 1, KDR CD309 Hematopoietic cells and progenitor cells von Willebrand factor Platelets Table 2 Endothelial markers and their expression on non-endothelial cells.
The most frequent ultimate cause of death is myocardial arrest. In many cases this is due to myocardial hypoxia, generally arising from failure of the coronary macro- and microcirculation to deliver ...enough oxygenated red cells to the cardiomyocytes. The principle reason for this is occlusive thrombosis, either by isolated circulating thrombi, or by rupture of upstream plaque. However, an additionally serious pathology causing potentially fatal stress to the heart is extra-cardiac disease, such as pulmonary hypertension. A primary cause of the latter is pulmonary embolus, considered to be a venous thromboembolism. Whilst the thrombotic scenario has for decades been the dominating paradigm in cardiovascular disease, these issues have, until recently, been infrequently considered in cancer. However, there is now a developing view that cancer is also a thrombotic disease, and notably a disease predominantly of the venous circulation, manifesting as deep vein thrombosis and pulmonary embolism. Indeed, for many, a venous thromboembolism is one of the first symptoms of a developing cancer. Furthermore, many of the standard chemotherapies in cancer are prothrombotic. Accordingly, thromboprophylaxis in cancer with heparins or oral anticoagulation (such as Warfarin), especially in high risk groups (such as those who are immobile and on high dose chemotherapy), may be an important therapy. The objective of this communication is to summarise current views on the epidemiology and pathophysiology of arterial and venous thrombosis in cancer.
Hemoxygenase-1 in Cardiovascular Disease Idriss, Naglaa K., MSc; Blann, Andrew D., PhD; Lip, Gregory Y.H., MD
Journal of the American College of Cardiology,
09/2008, Volume:
52, Issue:
12
Journal Article
Peer reviewed
Open access
Hemoxygenase-1 in Cardiovascular Disease Naglaa K. Idriss, Andrew D. Blann, Gregory Y. H. Lip Hemoxygenase (HO)-1 is an inducible isoform of the first and rate-controlling enzyme of the degradation ...of heme into iron, carbon monoxide, and biliverdin, the latter being subsequently converted into bilirubin. Anti-inflammatory, antiapoptotic, angiogenic, and cytoprotective functions are attributable to carbon monoxide and/or bilirubin. We offer a comprehensive overview of the biochemistry, physiology, and pathophysiology of HO-1 in relation to cardiovascular disease, presenting some of the emerging evidence in support of the induction of HO-1 in the pathophysiology of cardiovascular disease, with therapeutic implications.
Recent research has recognised new populations of non-hematopoietic cells in the blood. One of these, circulating endothelial cells (CECs), often defined by the expression of membrane glycoprotein ...CD146, are rarely found in the blood in health, but raised numbers are present in a wide variety of human conditions, including inflammatory, immune, infectious, neoplastic and cardiovascular disease, and seem likely to be evidence of profound vascular insult. An additional population are endothelial progenitor cells, defined by the co-expression of endothelial and immaturity cell surface molecules and also by the ability to form colonies in vitro. Although increased numbers of CECs correlate with other markers of vascular disease, questions remain regarding the precise definition, cell biology and origin of CECs. For example, they may be damaged, necrotic or apopototic, or alive, and could possess procoagulant and/or proinflammatory properties. However, since these cells seem to be representative of in situ endothelium, their phenotype may provide useful information. Indeed, whatever their phenotype, there is growing evidence that CECs may well be a novel biomarker, the measurement of which will have utility in various clinical settings related to vascular injury. Despite this promise, progress is impeded by the diversity of methodologies used to detect these cells. Accordingly, results are sometimes inconclusive and even conflicting. Nevertheless, increased CECs predict adverse cardiovascular events in acute coronary syndromes, suggesting they may move from being simply a research index to having a role in the clinic. The objective of the present communication is to condense existing data on CECs, briefly compare them with progenitor cells, and summarise possible mechanism(s) by which they may contribute to vascular pathology.
Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG). We sought to determine the diagnostic validity of plasma biomarkers of i) inflammation (marked by ...interleukin-6 IL-6 and high-sensitivity C-reactive protein hs-CRP), ii) extracellular matrix remodelling (matrix metalloproteinase MMP-9, tissue inhibitor of matrix metalloproteinase TIMP-1) and iii) the prothrombotic state (tissue factor and von Willebrand factor vWF) in the risk prediction of post-operative AF. Samples were obtained preoperatively from peripheral/femoral vein and from intracardiac chambers (right atrium RA, the right atrial appendage RAA, the left atrium LA and the left atrial appendage LAA) amongst 100 consecutive patients free of AF and inflammatory disease undergoing elective CABG. Biomarker concentrations were related to incident AF (30 days). At 30 days post CABG, 30 patients were proven to have had AF. Concentrations of tissue factor (TF) and vWF were unrelated to postoperative AF. Peripheral (p=0.018), and intracardiac levels (RAA (p=0.029) and LA (p=0.026)) of hs-CRP were associated with the presence of AF after CABG. Intracardiac levels of IL-6 in samples from the RAA (p=0.031), LA (p=0.042) and LAA (p=0.006), and MMP-9 in the LAA sample were also associated with AF (p=0.007). Our data suggest that an intra-cardiac inflammatory environment that is manifest peri-operatively may predispose to the development of post-operative AF. This intracardiac inflammatory state was reflected by increased peripheral hs-CRP levels. These differences may indicate local substrate abnormalities contributing to the development of AF post-operatively.
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