Complement system and small HDL particles are associated with subclinical atherosclerosis in SLE patients

Parra, Sandra; Vives, G; Ferré, Raimón; Gonzàlez, Marta; Guardiola, Montse; Ribalta, Josep; Castro, Antoni

doi:10.1016/j.atherosclerosis.2012.08.029

Cited by 35 publications

(24 citation statements)

References 43 publications

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“…Higher levels of circulating C3 have been shown to be associated with arterial calcification in different at-CVD risk populations including patients suffering from various autoimmune diseases like systemic lupus erythematosus (SLE) and psoriasis, and elderly patients(>70 years) (6, 7, 10, 12). In addition, follow-up studies in women with pre-existing CAD have shown that higher levels of circulating C3 could predict the complications of atherosclerosis (27).…”

Section: Discussionmentioning

confidence: 99%

“…Various studies have reported significant associations between complement proteins (e.g. C3, C4) and subclinical measures of atherosclerosis (6, 7) and demonstrated the activation of complement proteins within plaque in the arterial wall (8, 9). In light of the recent findings that complement protein C3 is higher in postmenopausal women (5), it is plausible to hypothesize that levels of complement proteins may play a potential role in explaining the higher risk of CVD after menopause (1).…”

Section: Introductionmentioning

confidence: 99%

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Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study

et al. 2015

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Background CVD risk increases in women after menopause. Recent data suggest higher levels of complement protein C3 and cardiovascular fat (CF) in postmenopausal women. Whether complement proteins are associated with early markers of atherosclerosis in healthy midlife women has never been evaluated. Additionally, the potential impact of the local CF on these associations has never been assessed. Methods Participants (n=100, age (mean(SD)):50.48(2.63), 50% premenopausal) were from the Study of Women's Health Across the Nation (SWAN). Arterial calcification (aortic-AC and coronary-CAC) and CF volumes around the heart and aorta (total heart-TAT and aortic perivascular adipose tissue-PVAT) were quantified using EBCT scans. AC and CAC were each evaluated as presence (Agatston scores>0) and extent of calcification (log (Agatston scores +1)). Logistic and linear regression models were used for statistical analysis. Results Adjusting for age, race, menopausal status and lipids, C3 was significantly associated with both presence and extent of AC and CAC, all P values <0.05. Associations between C3 and presence and extent of AC and CAC were explained by additional adjustment for logTAT and logPVAT, respectively. Association between C3 and log(AC+1) was more pronounced at higher volumes of logTAT (interaction-P=0.013) adjusting for study variables. No associations were found with C4. Conclusions Higher C3 was significantly associated with presence and greater extent of arterial calcification in midlife women. These associations were explained by higher volumes of CF, suggesting CF as a potential source of C3. C3 could be a potential non-invasive biomarker of early diagnosis of atherosclerosis. These findings need to be replicated in larger studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study

et al. 2015

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“…Venous thrombosis may also occur early in SLE and is associated with the presence of antibodies against cardiolipin 95 96. A recent study in patients with SLE has pointed out that increased complement levels correlate with increased levels of HDL in plasma and early signs of atherosclerosis such as thickening of the heart vessel wall 97. This is puzzling since low complement levels are common in patients with SLE, although the risk for cardiovascular disease is increased.…”

Section: Complement and Thrombosismentioning

confidence: 99%

The complement system in systemic lupus erythematosus: an update

2014

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The complement system plays a major role in the autoimmune disease, systemic lupus erythematosus (SLE). However, the role of complement in SLE is complex since it may both prevent and exacerbate the disease. In this review, we explore the latest findings in complement-focused research in SLE. C1q deficiency is the strongest genetic risk factor for SLE, although such deficiency is very rare. Various recently discovered genetic associations include mutations in the complement receptors 2 and 3 as well as complement inhibitors, the latter related to earlier onset of nephritis. Further, autoantibodies are a distinct feature of SLE that are produced as the result of an adaptive immune response and how complement can affect that response is also being reviewed. SLE generates numerous disease manifestations involving contributions from complement such as glomerulonephritis and the increased risk of thrombosis. Furthermore, since most of the complement system is present in plasma, complement is very accessible and may be suitable as biomarker for diagnosis or monitoring of disease activity. This review highlights the many roles of complement for SLE pathogenesis and how research has progressed during recent years.

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“…Though C1q and C4d deposition on platelets is not specific for SLE, this is associated with venous thrombosis [26]. One study also suggests that small dense HDL particles may activate the complement system and are related to subclinical atherosclerosis in SLE patients [27]. …”

Section: The Role Of the Complement System In Human Slementioning

confidence: 99%

Complement in Lupus Nephritis: New Perspectives

2015

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Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Summary: Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. Key Messages: SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.

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Complement system and small HDL particles are associated with subclinical atherosclerosis in SLE patients

Cited by 35 publications

References 43 publications

Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study

Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study

The complement system in systemic lupus erythematosus: an update

Complement in Lupus Nephritis: New Perspectives

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