C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors

Nilsson, Bo; Hamad, Osama A.; Åhlström, Håkan; Kullberg, Joel; Johansson, Lars; Lindhagen, Lars; Haenni, Arvo; Ekdahl, Kristina Nilsson; Lind, Lars

doi:10.1111/eci.12275

Cited by 71 publications

(75 citation statements)

References 32 publications

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“…We found that in 1016 70-year old men and women, the plasma levels of C3a-desArg, C3, and C4 were all highly positively correlated with CVD risk factors (Nilsson et al, 2014). In particular, C3 was strongly correlated with these risk factors, with high BMI, abdominal fat distribution, blood pressure, triglycerides, blood glucose, and indicators of MetS all being linked to high plasma levels of C3.…”

Section: Alternative Pathway Activation and Generation Of C3a And C5amentioning

confidence: 78%

“…Indirect evidence that similar activation occurs in vivo comes from the observation that disorders in which cholestasis occurs, such as primary biliary cirrhosis and sclerosing cholangitis, lead to greatly elevated levels of C3 in the plasma (Gardinali et al, 1998;Jones et al, 1978). Consistent with a non-inflammation-related explanation for the regulation of C3 and C4 in obese individuals is the finding that C3 and C4 levels significantly decline after a combined treatment involving a gastric bypass operation and a 4-week diet (Nilsson et al, 2014). The surgical intervention is bound to induce inflammation, but despite this induction of inflammation, the levels of C3 and C4 are both reduced after weight loss.…”

Section: Complement Component Production By Adipocytesmentioning

confidence: 98%

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The role of complement factor C3 in lipid metabolism

Barbu

Hamad

Lind

et al. 2015

Molecular Immunology

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Section: Alternative Pathway Activation and Generation Of C3a And C5amentioning

confidence: 78%

Section: Complement Component Production By Adipocytesmentioning

confidence: 98%

The role of complement factor C3 in lipid metabolism

Barbu

Hamad

Lind

et al. 2015

Molecular Immunology

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“…The highly bioactive anaphylatoxins C3a and C5a, generated by activation of C3 and C5, are associated with increased risk in coronary heart disease (Speidl et al, 2005;Distelmaier et al, 2009), and C3a-and C5a receptors are expressed in human coronary plaques (Oksjoki et al, 2007). Recently Nilsson et al established that plasma C3, C4 and the activation fragment C3a-desArg were strongly related with adipose tissue volume and established risk factors for cardiovascular diseases (Nilsson et al, 2014).…”

Section: Evidence For Complement Activation In Coronary Heart Diseasementioning

confidence: 99%

A vital role for complement in heart disease

Lappegård

Garred

Jonasson

et al. 2014

Molecular Immunology

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Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

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“…C3 and C4 proteins are strongly associated with abdominal adiposity and visceral adipose tissue in human related studies (10). In mouse models, increased C3 and C4 deposition have been found connected to the adventitial and medial fibers including collagen and elastin at early time points prior to luminal lesion development (8).…”

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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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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C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors

Abstract: Background In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals.

Cited by 71 publications

References 32 publications

The role of complement factor C3 in lipid metabolism

The role of complement factor C3 in lipid metabolism

A vital role for complement in heart disease

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

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