The role of monocytes in atherosclerotic coronary artery disease
ABSTRACT Inflammation plays a key role in the pathogenesis of atherosclerosis. The more we discover about the molecular pathways involved in atherosclerosis, the more we perceive the importance of monocytes in this process. Circulating monocytes are components of innate immunity, and many pro-inflammatory cytokines and adhesion molecules facilitate their adhesion and migration to the vascular endothelial wall. In addition to the accumulation of lipids and formation of atherogenic 'foam' cells, monocytes may promote atherosclerotic plaque growth by production of inflammatory cytokines, matrix metalloproteinases, and reactive oxidative species. However, the contribution of monocytes to atherogenesis is not only limited to tissue destruction. Monocyte subsets are also involved in intraplaque angiogenesis and tissue reparative processes. The aim of this overview is to discuss the mechanisms of monocyte activation, the pivotal role and importance of activated monocytes in atherosclerotic coronary artery disease, their implication in the development of acute coronary events, and their potential in cardiovascular reparative processes such angiogenesis.
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ABSTRACT: Acute myocardial infarction (AMI) is a common and complex disease; pathogenesis of AMI is not completely understood and genetic, clinical and phenotypic variables are involved in the disease’s history. The aim of this paper was to assess: 1) the predictive capacity of Artificial Neural Networks (ANNs) in consistently distinguishing the two different conditions (AMI or control). 2) the identification of the variables with the maximal amount of relevant information for AMI. Genetic variances in inflammatory genes, along with clinical and classical risk factors from 149 AMI patients and 72 healthy subjects were investigated. From the data base of this case/control study 36 genetic, clinical and phenotypic variables were selected. The TWIST system, an evolutionary algorithm able to remove redundant and noisy information from complex data sets, further selected 18 variables. Moreover, fitness, sensitivity, specificity, overall accuracy and areas under the receiver-operating curves (AUC) of the 18 selected variables associated with AMI risk were investigated. Our findings showed that ANNs are useful in distinguishing risk factors selectively associated with the disease. Finally, the new mix of variables, including classical risk factors and genetic markers, generated a new risk cluster of variables able to discriminate between AMI and control subjects with an overall accuracy of 90%. This approach may be used to assess individual AMI risk in unaffected subjects with increased risk of the disease such as, first relative with positive parental history of cardiovascular diseases.Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) 03/2015; 12(3):159-166. DOI:10.2174/1875692113666150116232904
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ABSTRACT: Hypothesis Atherosclerotic cardiovascular complications are the leading cause of death in diabetic patients. Monocyte adhesion is an early event for atherogenesis. Previous studies demonstrated that dark-skin berries had cardiovascular protective effects. We hypothesize that SB powder may reduce monocyte adhesion in leptin receptor-deficient (db/db) diabetic mice. Methods Wild-type and db/db mice were fed with chow or supplemented with SB powder. Anthocyanins in SB powder were identified using mass spectrometry. Mouse monocytes were incubated with mouse aorta. Monocyte adhesion was counted under microscopy. Inflammatory or metabolic markers in blood or tissue were analyzed using immunological or biochemical methods. Results SB powder significantly reduced monocyte adhesion to aorta from diabetic db/db mice compared to regular chow. The increased monocyte adhesion to aorta was normalized in db/db mice treated with ≥5% of SB powder for 4 weeks. Increased contents of NAPDH oxidase-4, heat shock factor-1, monocyte chemotactic protein (MCP)-1, intracellular adhesion molecule (ICAM)-1, P-selectin, tumor necrosis factor-α, plasminogen activator inhibitor (PAI)-1 and urokinase plasminogen activator in aorta or heart apex, elevated plasma PAI-1 and MCP-1 were detected in db/db mice on chow compared to wild-type mice on the same diet. 5% SB powder inhibited the increases of inflammatory, fibrinolytic or stress regulators in aorta or heart apex of db/db mice. Monocyte adhesion positively correlated with blood glucose, cholesterol, body weight, heart MCP-1, PAI-1 or ICAM-1. Conclusion The findings suggest that SB powder attenuated monocyte adhesion to aorta of db/db mice, which was potentially mediated through inhibiting the inflammatory, stress and/or fibrinolyic regulators.Canadian Journal of Diabetes 10/2014; DOI:10.1016/j.jnutbio.2014.03.016 · 0.46 Impact Factor
- Atherosclerosis 08/2014; 235(2):e217. DOI:10.1016/j.atherosclerosis.2014.05.644 · 3.97 Impact Factor