scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism

01 Feb 2015-Brazilian Journal of Medical and Biological Research (Associação Brasileira de Divulgação Científica)-Vol. 48, Iss: 2, pp 161-166
TL;DR: MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.
Abstract: Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
TL;DR: There is evidence that serum C‐reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events.
Abstract: Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high-sensitivity assays for serum C-reactive protein have shown a consistent association between cardiovascular disease risk and serum C-reactive protein concentrations. C-reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C-reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C-reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C-reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C-reactive protein genetic polymorphisms on baseline plasma C-reactive protein levels.

115 citations

Journal ArticleDOI
TL;DR: MAC-SMC communication affects factors and molecules that could alter ECM composition and neo-angiogenesis, features that could directly dictate the progression of atheroma towards the vulnerable plaque.

53 citations

Journal ArticleDOI
TL;DR: It is reported for the first time that short-term colchicine therapy significantly reduces the local production of coronary chemokines, in part by attenuating production of these mediators by monocytes.

31 citations

Journal ArticleDOI
TL;DR: Analysis of correlation between expression of two members of the cytokine family and the processes of inflammation and angiogenesis related to atherosclerosis finds that placental growth factor and chemokine CX3XL1 (fractalkine) promote inflammatory cell infiltration,Angiogenesis and plaque rupture.

19 citations

Journal ArticleDOI
TL;DR: Combining hs-CRP with National Institutes of Health Stroke Scale could predict outcome with satisfying clinical accuracy both in LAA and SAO subtype.
Abstract: Background: High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker that is associated with the outcomes of ischemic stroke. However, the role of hs-CRP levels in the functional outc...

17 citations

References
More filters
Journal ArticleDOI
TL;DR: VH-IVUS TCFA was associated with nonrestenotic and total MACE on individual plaque analysis, and noncalcified VHTCFA wasassociated with nonRestenoticand total Mace on whole-patient analysis, demonstrating that VH- IVUS can identify plaques at increased risk of subsequent events.
Abstract: Objectives: The purpose of this study was to determine whether thin-capped fibroatheromata (TCFA) identified by virtual histology intravascular ultrasound (VH-IVUS) are associated with major advers...

442 citations


"Role of chemokines in promoting ins..." refers background in this paper

  • ...When blood flows in the vessel, a thrombus appears as a shining crumbling echo (8)....

    [...]

Journal ArticleDOI
TL;DR: Stable peptide inhibitors are designed that specifically disrupt proinflammatory CCL5-CXCL4 interactions, thereby attenuating monocyte recruitment and reducing atherosclerosis without the aforementioned side effects.
Abstract: Atherosclerosis is characterized by chronic inflammation of the arterial wall due to chemokine-driven mononuclear cell recruitment. Activated platelets can synergize with chemokines to exacerbate atherogenesis; for example, by deposition of the chemokines platelet factor-4 (PF4, also known as CXCL4) and RANTES (CCL5), triggering monocyte arrest on inflamed endothelium. Homo-oligomerization is required for the recruitment functions of CCL5, and chemokine heteromerization has more recently emerged as an additional regulatory mechanism, as evidenced by a mutual modulation of CXCL8 and CXCL4 activities and by enhanced monocyte arrest resulting from CCL5-CXCL4 interactions. The CCL5 antagonist Met-RANTES reduces diet-induced atherosclerosis; however, CCL5 antagonism may not be therapeutically feasible, as suggested by studies using Ccl5-deficient mice which imply that direct CCL5 blockade would severely compromise systemic immune responses, delay macrophage-mediated viral clearance and impair normal T cell functions. Here we determined structural features of CCL5-CXCL4 heteromers and designed stable peptide inhibitors that specifically disrupt proinflammatory CCL5-CXCL4 interactions, thereby attenuating monocyte recruitment and reducing atherosclerosis without the aforementioned side effects. These results establish the in vivo relevance of chemokine heteromers and show the potential of targeting heteromer formation to achieve therapeutic effects.

402 citations


"Role of chemokines in promoting ins..." refers background in this paper

  • ...A study suggests that the binding of MCP-1 to its receptor CCR2 plays an important role in the initiation and progression of AS (19)....

    [...]

Journal ArticleDOI
TL;DR: Compared to other methods, carotid plaque burden was the strongest cross-sectional predictor of CACS, and its clinical utility as predictor of future cardiovascular events is being evaluated in the BioImage study.
Abstract: Objectives The purpose of this study was to compare carotid plaque burden, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and abdominal aortic diameter (AAD) to coronary artery calcium score (CACS) in people without known cardiovascular disease. Background The clinical utility of risk factors to predict cardiovascular events is limited. Detection of subclinical atherosclerosis by noninvasive tests such as CACS, cIMT, carotid plaque burden, AAD, and ABI may improve risk prediction above that of established risk scoring models, namely, Framingham Risk Score. Methods The High Risk Plaque BioImage study investigated 6.101 asymptomatic persons and reports baseline CACS, cIMT, ABI, and AAD. In addition, we present findings from a new 3-dimensional–based ultrasound approach, where the carotid artery was investigated in cross section from proximal in the neck to as distal as possible. From the resulting 10-s video, plaque was outlined on cross-sectional images and all plaque areas were summarized into “plaque burden.” Results The mean age was 68.8 years, and 65.3% of subjects had intermediate Framingham Risk Score (6% to 20% 10-year risk). Carotid plaques were identified in 78% of cases, abnormal ABI in 10%, AAD >20 mm in 28%, and coronary calcium in 68% of participants. Carotid plaque burden was found to correlate stronger with CACS (chi-square 450, p Conclusions In the BioImage study, a new 3-dimensional–based ultrasound method identified more carotid plaques than in previous studies. Compared to other methods, carotid plaque burden was the strongest cross-sectional predictor of CACS, and its clinical utility as predictor of future cardiovascular events is being evaluated in the BioImage study. (BioImage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725 )

234 citations


"Role of chemokines in promoting ins..." refers background in this paper

  • ...(14) reported that plaques with thin fibrous caps and large lipid cores were easy to rupture when using IVUS....

    [...]

Journal ArticleDOI
TL;DR: This review will give a comprehensive summary to highlight those chemokines addressed in different models of atherosclerosis and vascular injury to date and discuss recent developments scrutinizing heterophilic interactions of chemokine interactions that have advanced the authors' understanding of howChemokines control vascular inflammatory responses.
Abstract: Atherosclerosis is considered to be a chronic inflammatory disease of the vessel wall that encompasses the accumulation of lipids, and it is critically shaped by the recruitment of leucocytes during all phases of the disease. In addition, the progression of atherosclerosis is determined by a disturbed equilibrium of immune responses. Chemokines and their receptors are instrumental in orchestrating the influx of leucocytes to the vascular wall, but also seem to regulate immune functions. Recent work has shed light on the apparent redundancy and the robustness of the chemokine system and has also provided evidence for its specialized role in the regulation of specific functions and trafficking of leucocyte subpopulations. This review will give a comprehensive summary to highlight those chemokines addressed in different models of atherosclerosis and vascular injury to date. In addition, we will discuss recent developments scrutinizing heterophilic interactions of chemokines that have advanced our understanding of how chemokines control vascular inflammatory responses.

209 citations


"Role of chemokines in promoting ins..." refers background in this paper

  • ...(24) found that RANTESmRNA expression existed in human atherosclerotic plaques....

    [...]

Journal ArticleDOI
27 Jun 2012-PLOS ONE
TL;DR: It is suggested that in regressing plaque CD68+ cells preferentially express genes that reduce cellular adhesion, enhance cellular motility, and overall act to suppress inflammation.
Abstract: We have developed a mouse model of atherosclerotic plaque regression in which an atherosclerotic aortic arch from a hyperlipidemic donor is transplanted into a normolipidemic recipient, resulting in rapid elimination of cholesterol and monocyte-derived macrophage cells (CD68+) from transplanted vessel walls. To gain a comprehensive view of the differences in gene expression patterns in macrophages associated with regressing compared with progressing atherosclerotic plaque, we compared mRNA expression patterns in CD68+ macrophages extracted from plaque in aortic aches transplanted into normolipidemic or into hyperlipidemic recipients. In CD68+ cells from regressing plaque we observed that genes associated with the contractile apparatus responsible for cellular movement (e.g. actin and myosin) were up-regulated whereas genes related to cell adhesion (e.g. cadherins, vinculin) were down-regulated. In addition, CD68+ cells from regressing plaque were characterized by enhanced expression of genes associated with an anti-inflammatory M2 macrophage phenotype, including arginase I, CD163 and the C-lectin receptor. Our analysis suggests that in regressing plaque CD68+ cells preferentially express genes that reduce cellular adhesion, enhance cellular motility, and overall act to suppress inflammation.

101 citations

Related Papers (5)