Elevated Circulating Levels of Monocyte Chemoattractant Protein-1 in Patients With Restenosis After Coronary Angioplasty

Cipollone, Francesco; Marini, Matteo; Fazia, Maria; Pini, Barbara; Iezzi, Annalisa; Reale, Marcella; Paloscia, Leonardo; Materazzo, Guido; D’Annunzio, E; Conti, Pio; Chiarelli, Francesco; Cuccurullo, Franco; Mezzetti, Andrea

doi:10.1161/01.atv.21.3.327

Cited by 199 publications

(157 citation statements)

References 51 publications

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“…The third, enhanced formation of a fibrous cap, was not observed. However, there was no suggestion of plaque destabilization (25) in the mPGES-1 Ϫ/Ϫ LDLR Ϫ/Ϫ s. Expression of both PGIS and TxS is increased in endothelial cells, and the increase in the ratio of VSMCs relative to foam cells is associated with an increase in the proportion of neointimal cells expressing PGIS consequent to deletion of mPGES-1. Increased endothelial expression of both PGIS and TxS suggests removal of an mPGES-1-derived regulatory restraint on these enzymes in the mPGES-1 Ϫ/Ϫ LDLR Ϫ/Ϫ s.…”

Section: Discussionmentioning

confidence: 90%

“…EP1 and EP3 mediate PGE 2 -induced vasoconstriction (22,23), and PGE 2 can either activate platelets by EP3 or, at higher concentrations, inhibit platelet aggregation by the IP (24). A further layer of complexity has been added by the observation that COX-2, EP4, and metalloproteinase (MMP) 9 are all upregulated in human atherosclerotic plaque ex vivo (25), and that COX-2-dependent extracellular matrix-dependent activation of MMP9 is mediated by the EP4 in vitro (26).…”

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confidence: 99%

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Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis

Wang

Zukas

Hui

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

184

165

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Prostaglandin (PG) E2 is formed from PGH2 by a series of PGE synthase (PGES) enzymes. Microsomal PGES-1 ؊/؊ (mPGES-1 ؊/؊ ) mice were crossed into low-density lipoprotein receptor knockout (LDLR ؊/؊ ) mice to generate mPGES-1 ؊/؊ LDLR ؊/؊ s. Urinary 11␣-hydroxy-9, 15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M) was depressed by mPGES-1 deletion. Vascular mPGES-1 was augmented during atherogenesis in LDLR ؊/؊ s. Deletion of mPGES-1 reduced plaque burden in fat-fed LDLR ؊/؊ s but did not alter blood pressure. mPGES-1 ؊/؊ LDLR ؊/؊ plaques were enriched with fibrillar collagens relative to LDLR ؊/؊ , which also contained small and intermediate-sized collagens. Macrophage foam cells were depleted in mPGES-1 ؊/؊ LDLR ؊/؊ lesions, whereas the total areas rich in vascular smooth muscle cell (VSMC) and matrix were unaltered. mPGES-1 deletion augmented expression of both prostacyclin (PGI 2) and thromboxane (Tx) synthases in endothelial cells, and VSMCs expressing PGI synthase were enriched in mPGES-1 ؊/؊ LDLR ؊/؊ lesions. Stimulation of mPGES-1 ؊/؊ VSMC and macrophages with bacterial LPS increased PGI 2 and thromboxane A2 to varied extents. Urinary PGE-M was depressed, whereas urinary 2,3-dinor 6-keto PGF 1␣, but not 2,3-dinor-TxB2, was increased in mPGES-1 ؊/؊ LDLR ؊/؊ s. mPGES-1-derived PGE2 accelerates atherogenesis in LDLR ؊/؊ mice. Disruption of this enzyme retards atherogenesis, without an attendant impact on blood pressure. This may reflect, in part, rediversion of accumulated PGH 2 to augment formation of PGI 2. Inhibitors of mPGES-1 may be less likely than those selective for cyclooxygenase 2 to result in cardiovascular complications because of a divergent impact on the biosynthesis of PGI 2.atherosclerosis ͉ cyclooxygenase ͉ macrophage ͉ vascular smooth muscle cell R ecent placebo-controlled trials have revealed that nonsteroidal antiinflammatory drugs (NSAIDs) selective for inhibition of cyclooxygenase 2 (COX-2) confer a small but absolute risk of myocardial infarction and stroke (1-5). Mechanistically, this is attributable to suppression of COX-2-derived prostacyclin (PGI 2 ; ref. 6), which acts as a general restraint on endogenous stimuli, including platelet COX-1-derived thromboxane (Tx) A 2 , to platelet activation, vascular proliferation and remodeling, hypertension, atherogenesis, and cardiac function (7-13). Precise estimates of the incidence of this risk are not available. However, the relative risk is small and likely to be conditioned by such factors as drug exposure, underlying cardiovascular risk of the patients exposed and concomitant therapies (6, 13). However, the consumption of celecoxib, rofecoxib, and valdecoxib by millions has raised concern that many patients may have suffered cardiovascular adverse events from these drugs.Inhibitors of COX-2 afford relief from pain and inflammation principally by suppressing prostaglandin (PG) E 2 and PGI 2 . Deletion and͞or antagonism of receptors for both of these PGs modulate the response to both painful and inflammatory stimuli (14-17). Altho...

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Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 99%

Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis

Wang

Zukas

Hui

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

184

165

View full text Add to dashboard Cite

show abstract

“…Interestingly, a rapid and prolonged production of MCP-1 is reported in patients who present with restenosis after balloon angioplasty. 24,33 Cipollone et al 24 demonstrated that patients with restenosis have a prolonged increase in plasma MCP-1, whereas nonrestenotic patients have only a transient increase in plasma MCP-1. Thus, human arteries with underlying hypercholesterolemia and/or atherosclerosis are likely to represent prolonged production of MCP-1 after arterial injury.…”

Section: Role Of Mcp-1 In Cardiovascular Diseasementioning

confidence: 99%

“…In this regard, we devised a new strategy for anti-MCP-1 gene therapy by transfecting mutant MCP-1 gene. 17,24 This strategy might be useful for clarifying the role of MCP-1 under pathophysiologic conditions in vivo. In this review, we describe the role of MCP-1 in cardiovascular diseases and introduce recent work that addresses the usefulness of anti-MCP-1 gene therapy.…”

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confidence: 99%

Molecular Mechanisms Mediating Inflammation in Vascular Disease

Egashira

2003

Hypertension

147

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Abstract-There are several clinical challenges for the treatment of intractable cardiovascular diseases, including restenosis, atherosclerotic complications resulting from plaque rupture, severe tissue ischemia, and heart failure. Emerging evidence suggests that an inflammatory process is involved in the pathogenesis of such intractable diseases.In particular, inflammatory responses to arterial injury, which cause continuous recruitment and activation of monocytes mainly through activation of the monocyte chemoattractant protein- The effects of MCP-1 are mediated mainly through CC chemokine receptor 2 (CCR2). 3,4 MCP-1 causes chronic vascular inflammation and induces thrombosis, proliferation and migration of vascular smooth muscle cells, angiogenesis, and oxidative stress (Figure 1). Previous studies indicate that (1) MCP-1 production from endothelial cells, smooth muscle cells, and lesional leukocytes increases in the presence of endothelial dysfunction and atherosclerotic risk factors ( Figure 1); (2) MCP-1 expression is increased in atherosclerotic lesions 5,6 and injured arteries 7,8 ; and (3) eliminating MCP-1 function decreases neointimal hyperplasia after injury and atheroma formation in mice. 9 -12 We demonstrated that MCP-1 has an important role in coronary arteriosclerosis in a rat model of NO synthesis inhibition. [13][14][15][16][17] Emerging evidence suggests that MCP-1-mediated inflammatory disorders are involved in restenosis and atherosclerosis, as well as in other treatment-intractable cardiovascular diseases, such as posttransplantation arteriosclerosis, vascular remodeling owing to hypertension, myocarditis/cardiomyopathy, and cardiac dysfunction and remodeling after myocardial infarction. 18 -23 Therefore, therapeutic strategies targeting MCP-1 might become useful and practical treatments for cardiovascular diseases that are intractable with conventional therapies. In this regard, we devised a new strategy for anti-MCP-1 gene therapy by transfecting mutant MCP-1 gene. 17,24 This strategy might be useful for clarifying the role of MCP-1 under pathophysiologic conditions in vivo. In this review, we describe the role of MCP-1 in cardiovascular

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“…12 In several small case-control studies, plasma MCP-1 levels were found to be highest among patients with acute coronary syndromes (ACS), intermediate among patients with stable coronary disease, and lowest among healthy control subjects; however, there was considerable overlap in MCP-1 levels between the groups. [15][16][17] No prospective data are available evaluating the relation between plasma MCP-1 levels and outcomes in patients with ACS.…”

mentioning

confidence: 99%

Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes

et al. 2003

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Background-Monocyte chemoattractant protein-1 (MCP-1) is a chemokine responsible for the recruitment of monocytes to sites of inflammation. MCP-1 appears to play a critical role at multiple stages in atherosclerosis, including the initiation of the fatty streak, promotion of plaque instability, and remodeling after myocardial infarction. After adjustment for differences in baseline characteristics, ECG changes, troponin I, and C-reactive protein, an MCP-1 level Ͼ75th percentile (corresponding to the 90th percentile in the healthy volunteers) was associated with an increased risk of death or myocardial infarction through 10 months of follow-up (adjusted hazard ratio, 1.53; 95% CI, 1.09 to 2.14; Pϭ0.01). Conclusions-In a large cohort of patients with acute coronary syndromes, an elevated baseline level of MCP-1 was associated both with traditional risk factors for atherosclerosis as well as an increased risk for death or myocardial infarction, independent of baseline variables. Because it appears to play a crucial role at multiple stages of atherosclerosis, MCP-1 is attractive as a surrogate biomarker and merits further study as a potential therapeutic target.

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Elevated Circulating Levels of Monocyte Chemoattractant Protein-1 in Patients With Restenosis After Coronary Angioplasty

Cited by 199 publications

References 51 publications

Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis

Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis

Molecular Mechanisms Mediating Inflammation in Vascular Disease

Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes

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