Effects of interleukin-6 produced in coronary circulation on production of C-reactive protein and coronary microvascular resistance

Date, Hiroyuki; Imamura, Takuroh; Sumi, Takahiro; Ishikawa, Tetsunori; Kawagoe, Junji; Onitsuka, Hisamitsu; Kawamoto, Riichirou; Nagoshi, Toshiro; Eto, Tanenao

doi:10.1016/j.amjcard.2004.11.049

Cited by 10 publications

(4 citation statements)

References 18 publications

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“…These data have been confirmed by the discovery that CRP may be released not only from hepatocytes but also from other different cell types [39-41]. Taken together with previous observation from our group and others [38, 42, 43], regarding the active production of CRP within the coronary circulation of ACS patients and in cerebrovascular patients, the main question raised was related to the possible local effects exerted by CRP on the different cellular components of the atherosclerotic lesion. By biological and molecular point of view, CRP may promote endothelial function inducing adhesion molecules [44-47], favouring a pro-atherogenic phenotype via expression of TF [48], releasing MCP-1 [49] and other inflammatory cytokines [50, 51], increasing iNOS and superoxide production and decreasing eNOS, prostacyclin and tPA expression in endothelial cells [45, 52].…”

Section: Inflammatory Side Of Atherosclerosis:systemic Vs Local Inflsupporting

confidence: 83%

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

Cimmino

Loffredo

Morello

et al. 2017

CCR

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In the last twenty years, our comprehension of the molecular mechanisms involved in the formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its com-plications, such as rupture or ulceration. According to the new terminology, “vulnerable plaque” identi-fies an inflamed atherosclerotic lesion that is particularly prone to rupture. Once disrupted, prothrom-botic material is exposed to the flowing blood, thus activating coagulation cascade and platelet aggrega-tion, ultimately leading to acute thrombus formation within the coronary vessel. To date this is the key event underlying the clinical manifestations of acute coronary syndromes (ACS).The degree of vessel occlusion (complete vs. incomplete) and the time of blood flow cessation will define the severity of clinical picture. This phenomenon seems to be the final effect of a complex inter-action between different local and systemic factors, involving the degree of inflammation, type of cells infiltration and the rheological characteristics of blood flow at the site of plaque rupture, thrombogenic substrates within the atherosclerotic lesion and different soluble mediators, already present or acutely released in the circulating blood. This article will review currently available data on the pathophysiology of ACS, emphasizing the immunological and inflammatory aspects of vulnerable plaque. We may pos-tulate that intraplaque antigens and local microenvironment will define the immune-inflammatory re-sponse and cells phenotype, thus determining the severity of clinical manifestations.

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Section: Inflammatory Side Of Atherosclerosis:systemic Vs Local Inflsupporting

confidence: 83%

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

Cimmino

Loffredo

Morello

et al. 2017

CCR

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“…The strong correlation between high CRP levels (3 to 10 μg/mL) and diminished vascular reactivity in both peripheral and coronary circulations of human patients also supports the idea of CRP as a mediator of vascular dysfunction [36–39]. In the coronary circulation of patients with normal and diseased vessels, local CRP production directly correlated with the increase in microvascular resistance [40], a finding that agrees with the results presented in the present study.…”

Section: Discussionsupporting

confidence: 90%

C-reactive protein impairs coronary arteriolar dilation to prostacyclin synthase activation: Role of peroxynitrite

Hein

Qamirani

Ren

et al. 2009

Journal of Molecular and Cellular Cardiology

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Endothelium-derived vasodilators, i.e., nitric oxide (NO), prostacyclin (PGI 2 ) and prostaglandin E 2 (PGE 2 ), play important roles in maintaining cardiovascular homeostasis. C-reactive protein (CRP), a biomarker of inflammation and cardiovascular disease, has been shown to inhibit NOmediated vasodilation. The goal of this study was to determine whether CRP also affects endothelial arachidonic acid (AA)-prostanoid pathways for vasomotor regulation. Porcine coronary arterioles were isolated and pressurized for vasomotor study, as well as for molecular and biochemical analysis. AA elicited endothelium-dependent vasodilation and PGI 2 release. PGI 2 synthase (PGI 2 -S) inhibitor trans-2-phenyl cyclopropylamine blocked vasodilation to AA but not to serotonin (endotheliumdependent NO-mediated vasodilator). Intraluminal administration of a pathophysiological level of CRP (7 μg/mL, 60 minutes) attenuated vasodilations to serotonin and AA but not to nitroprusside, exogenous PGI 2 , or hydrogen peroxide (endothelium-dependent PGE 2 activator). CRP also reduced basal NO production, caused tyrosine nitration of endothelial PGI 2 -S, and inhibited AA-stimulated PGI 2 release from arterioles. Peroxynitrite scavenger urate failed to restore serotonin dilation, but preserved AA-stimulated PGI 2 release/dilation and prevented PGI 2 -S nitration. NO synthase inhibitor L-NAME and superoxide scavenger TEMPOL also protected AA-induced vasodilation. Collectively, our results suggest that CRP stimulates superoxide production and the subsequent formation of peroxynitrite from basal released NO compromises PGI 2 synthesis, and thus endothelium-dependent PGI 2 -mediated dilation, by inhibiting PGI 2 -S activity through tyrosine nitration. By impairing PGI 2 -S function, and thus PGI 2 release, CRP could promote endothelial dysfunction and participate in the development of coronary artery disease.

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“…These fi ndings suggest that epicardial adipose tissue is involved in a localized cytokine -infl ammatory pathway in the coronary circulation. We reported that plasma CRP and interleukin-6 levels are increased in the coronary circulation of patients with CAD compared with those without CAD [5,6] . Additionally, Ouchi et al reported that human adipose tissue expresses the CRP gene and the adiponectin gene and might partially account for elevated plasma CRP and adiponectin levels.…”

Section: Discussionmentioning

confidence: 90%

Reciprocal Production of Adiponectin and C-reactive Protein in Coronary Circulation of Patients with and without Coronary Artery Disease

Kawagoe¹,

Imamura²,

Date³

et al. 2008

Horm Metab Res

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Effects of interleukin-6 produced in coronary circulation on production of C-reactive protein and coronary microvascular resistance

Cited by 10 publications

References 18 publications

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

C-reactive protein impairs coronary arteriolar dilation to prostacyclin synthase activation: Role of peroxynitrite

Reciprocal Production of Adiponectin and C-reactive Protein in Coronary Circulation of Patients with and without Coronary Artery Disease

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