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Published on: May 6, 2014
The role of complement in atherosclerosis
Dorian O Haskard1, Joseph J Boyle, Justin C Mason
1Bywaters Centre for Vascular Inflammation, National Heart and Lung Institute, Imperial College, Hammersmith Hospital, London, UK. d.haskard@imperial.ac.uk
Insights
Recent research highlights the complement system's role in atherosclerosis, showing its involvement in lesion development and potential therapeutic targets. This review covers new findings on complement proteins and their impact on cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Atherosclerosis pathogenesis involves complement activation, but its precise functional roles remain under investigation.
- Recent studies continue to elucidate the complex interactions between the complement system and the development of atherosclerotic lesions.
Purpose of the Study:
- To review recent publications on the complement system's involvement in atherosclerosis.
- To highlight emerging findings regarding complement pathways and their implications for cardiovascular disease.
Main Methods:
- Review of recent scientific literature focusing on complement system components and atherosclerosis.
- Analysis of studies investigating complement protein associations with lipoproteins and cellular responses.
Main Results:
- Complement proteins and regulators are linked to high-density lipoproteins.
- Complement activation by modified LDL and downstream signaling pathways (C3a, C5a) are implicated.
- Membrane attack complex (C5b-9) formation and its regulation (CD59) are key.
- C1q shows a protective role in early lesion formation.
- Therapeutic agents (Crry-Ig, soluble C1 inhibitor) demonstrate efficacy in vascular injury models.
- Factor H polymorphism (Y402H) may increase atherosclerosis risk in specific populations.
Conclusions:
- The complement system is highly relevant to the field of atherosclerosis.
- Emerging research identifies novel therapeutic strategies targeting complement pathways for cardiovascular disease.
Purpose Of Review:
Although it has long been recognized that atherosclerotic lesions show evidence of complement activation, the functional roles of the complement system in atherogenesis are not yet fully resolved. This article highlights recent publications on the complement system in the atherosclerosis field.
Recent Findings:
There have been a number of recent papers reporting on the association of complement proteins and complement regulators with high density lipoproteins, complement activation by enzymatically-modified LDL, signalling pathways downstream of C3a and C5a receptors and membrane C5b-9 assembly, and the prevention of C5b-9 assembly on endothelial cells via upregulation of CD59 expression in response to arterial laminar flow. C1q has been found to play a protective role in early lesion formation in LDL receptor deficient mice, and Crry-Ig and soluble C1 inhibitor have both been shown to have therapeutic effects in models of vascular injury in ApoE deficient mice. The possibility that the Y402H Factor H polymorphism influences atherosclerosis has been supported in a recent paper showing increased risk in white hypertensive individuals.
Summary:
The articles that have emerged over the last year highlight the relevance of the complement system to the atherosclerosis field.
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