Regulation of Complement Protein Gene Expression

Colten, Harvey R.; Garnier, Gérard

doi:10.1201/b14212-11

Cited by 12 publications

(10 citation statements)

References 191 publications

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“…There are several possible explanations for our previous and current observations showing that an elevated C3 level is related to aortic stiffness. First, it may reflect an acute-phase response in which complement acts as an acute-phase reactant and is elevated during inflammation (27). This is unlikely, however, because the other acute-phase reactants we tested, fibrinogen and CRP, were not associated with aortic stiffness in these same patients.…”

Section: Discussionmentioning

confidence: 96%

Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus

Selzer¹,

Sutton-Tyrrell²,

Fitzgerald³

et al. 2004

Arthritis & Rheumatism

192

134

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Objective. To examine and compare risk factors for various stages of subclinical vascular disease in different vascular beds (carotid and aorta) in women with systemic lupus erythematosus (SLE) who have not yet developed clinical cardiovascular disease.Methods. This cross-sectional study was conducted in 214 women without clinical cardiovascular disease who were enrolled in the Pittsburgh Lupus Registry. B-mode ultrasound was used to measure carotid plaque and intima-media wall thickness (IMT). Doppler probes were used to collect pulse-wave velocity waveforms from the right carotid and femoral arteries as a measure of aortic stiffness. All risk factor data were collected on the day of the ultrasound examinations.Results. The mean ؎ SD age of the women was 45.2 ؎ 10.5 years and the median SLE disease duration was ϳ9 years. Sixty-eight (32%) of the women had at least 1 focal plaque. The mean ؎ SD IMT was 0.71 ؎ 0.1 mm, and the mean ؎ SD pulse-wave velocity was 5.96 ؎ 1.6 meters/second. Using logistic regression, we found that determinants of plaque included older age, higher systolic blood pressure, lower levels of high-density lipoprotein 3, and antidepressant use. Determinants of plaque severity were older age, higher systolic blood pressure, lower levels of albumin, and smoking. Independent determinants of the highest quartile of IMT were older age, higher pulse pressure, lower levels of albumin, elevated C-reactive protein levels, high cholesterol, and higher levels of glucose. Higher aortic stiffness was associated with older age, higher systolic blood pressure, higher C3 levels, lower white blood cell count, higher insulin levels, and renal disease.Conclusion. In women with SLE, the risk factors associated with carotid plaque and IMT are those typically associated with cardiovascular disease in the general population, whereas the risk factors associated with vascular stiffness include SLE-specific variables related to immune dysregulation and complement metabolism. The high prevalence of cardiovascular disease among lupus patients may result from both early adverse effects on vascular stiffening as well as later promotion of wall thickening and plaque through inflammatory-mediated processes. These observations provide clues for future mechanistic studies.Systemic lupus erythematosus (SLE) affects primarily women and causes chronic vascular inflammation. Women with SLE, particularly those under age 45 years, experience higher than expected rates of clinical cardiovascular disease, i.e., hypertension (1-3), myocardial infarction (1,4), and stroke (4). In addition to traditional cardiovascular risk factors, other factors specifically associated with SLE appear to be equally, if not more, important (5,6). It is likely that these factors are related to the underlying immune-mediated, inflammatory processes inherent in SLE.Although the pathogenesis of vascular disease in SLE is unknown, it is thought to be multifactorial and of atherosclerotic origin. Atherosclerosis involves both atherosis (fatty degeneration) an...

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Section: Discussionmentioning

confidence: 96%

Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus

Selzer¹,

Sutton-Tyrrell²,

Fitzgerald³

et al. 2004

Arthritis & Rheumatism

192

134

View full text Add to dashboard Cite

show abstract

“…Although complement activation and thus lower C3 levels are associated with increasing activity of SLE, complement can act as an acute-phase reactant, resulting in increasing levels in inflammatory states. 24 Furthermore, additional analyses found strong positive associations between C3 and C-reactive protein and fibrinogen, other inflammatory markers. It has been suggested that complement might be involved in the development of arterial wall lesions, and proposed modes of action include damage to the membrane or increased endothelium permeability, which could lead to the influx of plasma proteins into the arterial wall.…”

Section: Selzer Et Al Vascular Stiffness In Women With Slementioning

confidence: 97%

Vascular Stiffness in Women With Systemic Lupus Erythematosus

et al. 2001

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Abstract-Large-vessel manifestations of systemic lupus erythematosus (SLE), a multisystem disease characterized by disturbances in the immune system, include higher than expected rates of hypertension and cardiovascular disease. Reductions in the elasticity of central arteries may act as a marker of early changes that predispose to the development of major vascular disease. This study evaluated risk factors associated with aortic stiffness measured by pulse wave velocity (PWV) in women with SLE. We expected SLE-specific factors, especially variables indicative of inflammation and active disease, to be associated with increasing PWV. The study population included 220 women currently enrolled in the Pittsburgh Lupus Registry. All risk factor data were collected on the day of the ultrasound examinations. PWV waveforms were collected from the right carotid and femoral arteries by Doppler probes. The mean age of the women was 45.5Ϯ10.8 years, the median SLE disease duration approximated 9 years, and the mean PWV was 6.1Ϯ1.7 m/s. Multiple regression models were stratified by menopausal status. Among postmenopausal women, PWV risk factors were primarily traditional factors and included age, systolic blood pressure, family history of vascular disease, carotid plaque, creatinine, obesity, glucose, white cell count, and cumulative SLE organ damage. Among premenopausal women, PWV risk factors consisted of a mix of SLE-related and traditional variables and included higher C3 levels, presence of ds-DNA antibodies, nonuse of hydroxychloroquine, lower leukocyte count, higher mean arterial pressure, and carotid plaque. SLE-specific variables appeared to be associated with increases in aortic PWV, indicating central artery stiffening. This was seen most clearly among premenopausal women. This finding may partially explain the higher rates of cardiovascular disease and hypertension observed in young women with SLE. (Hypertension. 2001;37:1075-1082.)

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“…9), and tissue-specific complement synthesis may be important for supporting an immediate, local immune response. For example, human and rat lung epithelial cells and alveolar macrophages have been shown to synthesize complement proteins in vitro (1,8,41).…”

mentioning

confidence: 99%

Complement levels and activity in the normal and LPS-injured lung

Bolger

Ross

Jiang

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Complement, a complex protein system, plays an essential role in host defense through bacterial lysis, stimulation of phagocytosis, recruitment of immune cells to infected tissue, and promotion of the inflammatory response. Although complement is most well-characterized in serum, complement activity is also present in the lung. Here we further characterize the complement system in the normal and inflamed lung. By Western blot, C5, C6, and factor I were detected in bronchoalveolar lavage (BAL) at lower levels than in serum, whereas C2 was detected at similar levels in BAL and serum. C4 binding protein (C4BP) was not detectable in BAL. Exposure to lipopolysaccharide (LPS) elevated levels of C1q, factor B, C2, C4, C5, C6, and C3 in human BAL and C3, C5, and factor B in mouse and rat BAL. Message for C1q-B, C1r, C1s, C2, C4, C3, C5, C6, factor B, and factor H, but not C9 or C4BP, was readily detectable by RT-PCR in normal mouse lung. Exposure to LPS enhanced factor B expression, decreased C5 expression, and did not affect C1q-B expression in mouse and rat lung. BAL from rats exposed to LPS had a greater ability to deposit C3b onto bacteria through complement activation than did BAL from control rats. In summary, these data demonstrate that complement levels, expression, and function are altered in acute lung injury and suggest that complement within the lung is regulated to promote opsonization of pathogens and limit potentially harmful inflammation.

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Regulation of Complement Protein Gene Expression

Cited by 12 publications

References 191 publications

Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus

Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus

Vascular Stiffness in Women With Systemic Lupus Erythematosus

Complement levels and activity in the normal and LPS-injured lung

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