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Updated: Apr 9, 2026
A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
Published on: May 6, 2014
The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis
Anders Hovland1, Lena Jonasson2, Peter Garred3
1Coronary Care Unit, Division of Internal Medicine, Nordland Hospital, 8092 Bodø, Norway; Institute of Clinical Medicine, University of Tromsø, 9019 Tromsø, Norway.
Insights
Atherosclerosis involves innate immunity, specifically the complement system and toll-like receptors (TLRs). Targeting both may offer a potent anti-inflammatory therapy for atherosclerosis.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Inflammation Research
Background:
- Atherosclerosis remains a significant global health challenge.
- Innate immunity, particularly the complement system and toll-like receptors (TLRs), plays a crucial role in atherosclerotic inflammation.
- Previous research has shifted focus from adaptive to innate immunity in atherosclerosis.
Purpose of the Study:
- To explore the role of the complement system and TLRs in atherosclerosis pathogenesis.
- To investigate the potential of targeting the interplay between complement and TLRs as a therapeutic strategy.
Main Methods:
- Review of animal studies on complement inhibition (C3a, C5a).
- Analysis of human studies on modified LDL-cholesterol, complement, and TLR activation.
- Examination of histopathological and clinical data on innate immune system presence and upregulation in atherosclerotic lesions.
Main Results:
- Animal studies suggest complement inhibition reduces atherosclerosis.
- Modified LDL-cholesterol activates complement and TLRs, inducing inflammation in humans.
- Complement and TLRs are upregulated in atherosclerotic diseases, but interventions have yielded disappointing results.
Conclusions:
- The crosstalk between complement and TLRs is critical in atherosclerosis.
- Combined inhibition of complement and TLRs presents a promising anti-inflammatory therapeutic approach for atherosclerosis.
Abstract:
Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis.
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