Role of complement in the pathomechanism of atherosclerotic vascular diseases

Varga, Lilian; Füst, George; Prohászka, Zoltán

doi:10.1016/j.molimm.2009.04.028

Cited by 26 publications

(21 citation statements)

References 138 publications

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“…Plasma C3a levels remained elevated at the follow-up only in the LVD group and showed a significant association with the case- control status. As atherosclerosis has been shown to be strongly associated with complement activation [23], it is conceivable that the elevation of plasma C3a levels at follow-up in the LVD group is at least partly a consequence of the activation of the complement cascade by the underlying pathophysiological processes. These data, together with our findings of a positive correlation between C3a and C3 in LVD but not in cryptogenic stroke, indicate that in our study, brain ischemia in the cryptogenic stroke patients was not caused by the acceleration of a less active and milder form of LVD, as proposed by Bang et al [24,25].…”

Section: Discussionmentioning

confidence: 99%

Plasma C3 and C3a Levels in Cryptogenic and Large-Vessel Disease Stroke: Associations with Outcome

et al. 2011

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Background and Purpose: Inflammation seems to be a key player in the pathophysiology of stroke. In this study, we compared plasma C3 and C3a levels in cryptogenic and large-vessel disease (LVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at 3 months and 2 years. Methods: C3 and C3a levels in plasma of 79 cryptogenic stroke and 73 LVD stroke patients, sampled within 10 days and at 3 months after stroke, and age- and sex-matched control subjects from the Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assessed with the modified Rankin Scale. Results: Plasma C3 was increased in both stroke groups at both time points. Systemic elevation of C3a was limited to the acute phase in the cryptogenic stroke group, whereas plasma C3a levels in the LVD group were also elevated at the 3-month follow-up. In the LVD group, plasma C3 levels in the upper third at the 3-month follow-up were associated with an unfavorable outcome after 3 months independently of age and sex: odds ratio (OR) 5.56; 95% confidence interval (CI) 1.03–29.93; p = 0.045; as well as after 2 years: OR 4.75; 95% CI 1.11–20.30; p = 0.036. In the cryptogenic stroke group, high plasma C3a levels in the acute phase were associated with an unfavorable outcome after 3 months: OR 3.75; 95% CI 1.01–13.96; p = 0.049 in univariate analysis but not after adjustment for age and sex (p = 0.050). Conclusions: Plasma C3 and C3a levels are elevated in cryptogenic and LVD stroke and the predictive value of these markers may depend on stroke subtype. Further studies on the role of the complement system in ischemic stroke outcome based on larger patient populations and controlling for the effect of infections, are clearly warranted.

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Section: Discussionmentioning

confidence: 99%

Plasma C3 and C3a Levels in Cryptogenic and Large-Vessel Disease Stroke: Associations with Outcome

et al. 2011

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“…A C5a antagonist was not found to reverse the complexity of atherosclerotic histopathology; rather it significantly reduced plaque lipid areas [83] . Others see an application of complement activation inhibitors in the acute phases of chronic disease [84] . The aim of the experimental mouse model work is to identify complement factors which, if significantly important in the pathogenesis of disease, could be targeted in order to interfere with the natural progression of atheroma development.…”

Section: Perspectivementioning

confidence: 99%

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Francescut

Steiner²,

Byrne³

et al. 2011

J Innate Immun

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Atherosclerosis is a chronic progressive inflammatory disease which manifests in the arterial vascular tree. It is a major cause of cardiovascular morbidity and contributes significantly to mortality in the developed world. Triggers for this inflammatory process are elevated levels of cholesterol, bacterial infection and obesity. The immune response in atherosclerosis is essentially pro-atherogenic, leading to lipid accumulation and cellular changes within the arterial wall. Small-animal models of atherosclerosis are used to study the relevance of candidate factors (cells, genes, diets) in the development and progression of lesions. From a multidisciplinary viewpoint, there are challenges and limitations to this approach. Activation of complement determines or modifies the outcome of acute and chronic inflammation. This review dissects the role of complement in the early development as well as the progressive manifestation of murine atherosclerosis and the advances in knowledge provided by the use of specific mouse models. It gives a critical overview of existing models, analyses seemingly conflicting results obtained with complement-deficient mouse models, highlights the importance of interrelationships between pro-coagulpant activity, adipose tissue, macrophages and complement, and uncovers exciting avenues of topical research.

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“…the infarction since complement activation is known to be associated with both atherosclerosis and ischemia-reperfusion injury [8] .…”

Section: Commentmentioning

confidence: 99%

Is Stroke Etiology a Determining Factor for the Pattern of Secondary Immune Alterations?

Dressel¹

2011

Cerebrovasc Dis

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Role of complement in the pathomechanism of atherosclerotic vascular diseases

Cited by 26 publications

References 138 publications

Plasma C3 and C3a Levels in Cryptogenic and Large-Vessel Disease Stroke: Associations with Outcome

Plasma C3 and C3a Levels in Cryptogenic and Large-Vessel Disease Stroke: Associations with Outcome

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Is Stroke Etiology a Determining Factor for the Pattern of Secondary Immune Alterations?

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