The role of monocytes in atherosclerotic artery disease. Ann Med
University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, United Kingdom. Annals of Medicine
(Impact Factor: 3.89).
09/2010; 42(6):394-403. DOI: 10.3109/07853890.2010.497767
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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- "Previous studies have found that single nucleotide polymorphisms (SNPs), important genomic elements, can affect an individual's genetic susceptibility to various diseases, including CHD (Liu et al., 2014; Muiya et al., 2014; Wu et al., 2014; Yang et al., 2014). Mainly secreted by macrophages, matrix metalloproteinases (MMPs) are zinc-dependent enzymes that catalyze the degradation of connective tissue and extracellular matrix (Pamukcu et al., 2010; Benjamin and Khalil, 2012). MMPs are important in myocardial injury, vascular aneurysms, and remodeling (Blankenberg et al., 2003), and are thus suspected to be implicated in the pathogenesis of atherosclerosis and CHD (Yoon et al., 2002; Ketelhuth and Back, 2011). "
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ABSTRACT: Coronary heart disease (CHD) has become a leading cause of human deaths worldwide. Recent studied showed that polymorphisms of the matrix metalloproteinase (MMP) genes played important roles in extracellular matrix remodeling and contribute to the pathogenesis of vascular diseases. Here, we investigated whether these MMP gene polymorphisms were associated with CHD in Han Chinese. Our case-control study was involved with 1509 unrelated individuals, including 777 CHD cases and 732 controls. We selected a total of five polymorphisms whose genotypes were determined using Sequenom iPLEX technology. Our results showed there were no significant associations between the five MMP gene polymorphisms and CHD risk at either genotype or allele levels (P > 0.05). Further subgroup analyses by sex were also unable to reveal any significant association (P > 0.05). In conclusion, no significant associations were found between the five MMP gene polymorphisms and the risk of CHD in Han Chinese.
Available from: Massimo Buscema
- "Several studies confirmed that biomarkers of inflammation , such as increased blood levels of homocysteine , C-reactive protein , and cytokine levels      could be considered new risk factors for CHD and AMI. "
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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.
Available from: Trust Beta
- "The adhesion of monocytes to vascular endothelium initializes transmembrane migration of monocytes to vascular wall and the development of lipid-rich foam cells in atherogenetic lesions. A number of biological factors or conditions affect monocyte adhesion to cultured EC or vascular intima in animal models . Previous studies indicated that monocyte adhesion was enhanced under diabetic conditions . "
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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.
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.
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.
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.
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