Cardiovascular Disease and Inflammation: Novel Biomarkers of Inflammation and Endothelial Activation

2005 ◽  
Vol 2 (3) ◽  
pp. 191-203 ◽  
Author(s):  
Janos G. Filep
2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ting Wang

With the prevalence of antiviral therapy in the developed world, many HIV-1-infected people die of diseases other than AIDS. One of the emerging major causes is cardiovascular disease, leading to the prediction that the majority of HIV-1 patients are expected to develop cardiovascular complications. Endothelial dysfunction is thought to be a key event in the development of cardiovascular diseases, particularly atherosclerosis. Assays testing the effect of HIV-1 on endothelial activation shows that direct contact with HIV-1 infected T cells enhance endothelial cell activation to a greater extent than HIV-1 alone, suggesting an intracellular HIV-1 protein is responsible for endothelial activation. The HIV-1 viral protein Nef, which is responsible for T cell activation and maintenance of high viral loads in vivo , has been shown to mediate its own transfer to bystander cells. We demonstrate here for the first time that Nef induces nanotube-like conduits connecting T cells and endothelial cells. We also show that Nef is transferred from T cells to endothelial cells via these nanotubes, and is necessary and sufficient for endothelial cell activation. Moreover, we show that SIV-infected macaques exhibit endothelial Nef expression in coronary arteries. Nef expression in endothelial cells causes endothelial apoptosis, ROS and MCP-1 production. Interestingly, a Nef SH3 binding site mutant abolishes Nef-induced apoptosis and ROS formation and reduces MCP-1 production in endothelial cells, suggesting that the Nef SH3 binding site is critical for Nef effects on endothelial cells. Nef induces apoptosis of endothelial cells through an NADPH oxidase- and ROS-dependent mechanism, while Nef-induced MCP-1 production is NF-kB dependent. Taken together, these data suggest that Nef can mediate its transfer from T cells to endothelial cells through nanotubes to enhance endothelial dysfunction.Thus, Nef is a promising new therapeutic target for reducing the risk for cardiovascular disease in the HIV-1 positive population.


2014 ◽  
Vol 60 (1) ◽  
pp. 88-97 ◽  
Author(s):  
Nina P Paynter ◽  
Brendan M Everett ◽  
Nancy R Cook

Abstract BACKGROUND Risk prediction is an integral part of the current US guidelines for cardiovascular disease in women. Although current risk prediction algorithms exist to identify women at increased 10-year risk of cardiovascular disease (CVD), clinicians and researchers have been interested in developing novel biomarkers that might improve predictive accuracy further. These biomarkers have led to important insights into the pathophysiology of CVD, but results for their ability to improve prediction or guide preventive therapy have been mixed. The incidence of CVD is lower in women than men, and the effects of a number of traditional biomarkers on CVD risk differ in women compared to men. Both of these factors influence the ability to accurately predict CVD risk. CONTENT We review the distinctive aspects of CVD risk prediction in women, discuss the statistical challenges to improved risk prediction, and discuss a number of biomarkers in varying stages of development with a range of performance in prediction. SUMMARY A variety of biomarkers from different pathophysiologic pathways have been evaluated for improving CVD risk. While many have been incompletely studied or have not been shown to improve risk prediction in women, others, such as high-sensitivity troponin T, have shown promise in improving risk prediction. Increasing inclusion of women in CVD studies will be crucial to providing opportunities to evaluate future biomarkers.


2012 ◽  
Vol 2 (4) ◽  
pp. 393-397 ◽  
Author(s):  
Natalia Lazzarin ◽  
Giovambattista Desideri ◽  
Claudio Ferri ◽  
Herbert Valensise ◽  
Giulia Gagliardi ◽  
...  

2010 ◽  
Vol 160 (4) ◽  
pp. 583-594 ◽  
Author(s):  
Willibald Hochholzer ◽  
David A. Morrow ◽  
Robert P. Giugliano

2010 ◽  
Vol 2 (3) ◽  
pp. 66 ◽  
Author(s):  
Anna Meiliana ◽  
Andi Wijaya

BACKGROUND: The investigation of novel circulating serum and plasma biomarkers in patients with cardiovascular disease has been accelerating at a remarkable pace. New markers or tests are often presented too early to the medical profession, potentially leading to overuse and, thus, extra burden and costs to patients, the healthcare industry, and the economy. The challenge for clinicians and medical researchers is how to optimally apply existing and new markers/tests.CONTENT: Biomarkers are biological parameters that can be objectively measured and quantified as indicators of normal biologic processes, pathogenic processes, or responses to a therapeutic intervention. Typically thought of as disease process screening, diagnosing, or monitoring tools, biomarkers may also be used to determine disease susceptibility and eligibility for specific therapies. Cardiac biomarkers are protein components of cell structures that are released into circulation when myocardial injury occurs. They play a pivotal role in the diagnosis, risk stratification, and treatment of patients with chest pain and suspected acute coronary syndrome (ACS) as well as those with acute exacerbations of heart failure.SUMMARY: Active investigation has brought forward an increasingly large number of novel candidate markers but few have withstood the test of time and become integrated into contemporary clinical care because of their readily apparent diagnostic, prognostic, and/or therapeutic utility. With regard to the more novel biomarkers, careful thought is needed with regard to the appropriate target populations for discovery and validation, as well as the criteria used to sort out the contenders from the pretenders.KEYWORDS: biomarker, cardiovascular disease, atherosclerosis, acute myocardial infarction, heart failure, risk stratification, diagnosis, prognosis


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