Complement C3 and cleavage products in cardiometabolic risk

Onat, Altan; Can, Günay; Rezvani, Reza; Cianflone, Katherine

doi:10.1016/j.cca.2011.03.005

Cited by 106 publications

(81 citation statements)

References 91 publications

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“…In support of this hypothesis, studies have demonstrated that the localization/deposition of complement components (such as C1q, C3, C4 and C5) occurs in hypoxic myocardium (10)(11)(12)(13). Furthermore, mice deficient in C3, C5 or C6 have less severe I/R-induced myocardial injury compared with those of the wild-type (11).…”

Section: Discussionmentioning

confidence: 93%

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

Guo

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The optimal treatment for chronic intermittent hypoxia (CIH)-induced cardiovascular injuries has yet to be determined. The aim of the current study was to explore the potential protective effect and mechanism of a C1 inhibitor in CIH in the myocardium. The present study used a rat model of CIH in which complement regulatory protein, known as C1 inhibitor (C1INH), was administered to the rats in the intervention groups. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of proteins associated with the apoptotic pathway, such as B-cell lymphoma 2 (Bcl-2), Bax and caspase-3 were detected by western blot analysis. The expression of complement C3 protein and RNA were also analyzed. C1INH was observed to improve the cardiac function in rats with CIH. Myocardial myeloperoxidase activity, a marker of neutrophil infiltration, was significantly decreased in the C1INH intervention group compared with the CIH control group, and cardiomyocyte apoptosis was significantly attenuated (P<0.05). Western blotting and reverse transcription-polymerase chain reaction analysis indicated that the protein expression levels of Bcl-2 were decreased and those of Bax were increased in the CIH group compared with the normal control group, but the protein expression levels of Bcl-2 were increased and those of Bax were decreased in the C1INH intervention group, as compared with the CIH group. Furthermore, the CIH-induced expression and synthesis of complement C3 in the myocardium were also reduced in the C1INH intervention group. C1INH, in addition to inhibiting complement activation and inflammation, preserved cardiac function in CIH-mediated myocardial cell injury through an anti-apoptotic mechanism.

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Section: Discussionmentioning

confidence: 93%

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

Guo

Chen

et al. 2016

Experimental and Therapeutic Medicine

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“…The interplay across gender, hypertriglyceridemia, elevated CRP and HDL dysfunction in the development of cardiometabolic risk is illustrated in the Figure 2. Sex differences involve the joint role of the pro-inflammatory state, represented by elevated circulating Trg, CRP and HDL dysfunction, as well as a greater role of complement C3 in women (25,26). The Other elements of enhanced low-grade inflammation/oxidative stress such as increased cellular adhesion molecules and elevated serum 8-isoprostanes (27), shown to exist in cardiometabolic disorders, may well be involved.…”

Section: Sex Difference In Hdl Dysfunctionmentioning

confidence: 99%

Clinical biomarkers of high-density lipoprotein dysfunction among middle-aged Turks

Onat¹,

Can²,

Murat³

et al. 2012

Anadolu Kardiyol Derg

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Objective: Impaired function of high-density lipoprotein (HDL) particles generates cardiometabolic disorders in people prone to impaired glucose tolerance for which clinical biomarkers need delineation. Study design: Prospective population-based study. Methods: Totally, data of 2725 adults followed-up over 7.3±3.0 years were analyzed by Cox regression analysis. C-reactive protein (CRP), complement C3 (C3), triglycerides (Trg) and HDL-cholesterol were tested to predict risk for incident diabetes or coronary heart disease (CHD). Results: Beyond atherogenic dyslipidemia, high-Trg/normal HDL-cholesterol category was associated with elevated CRP and diabetes risk in women. Normotriglyceridemic men with normal HDL-cholesterol showed higher apolipoprotein A-I levels and higher diabetes risk than men having low HDL-cholesterol. Diabetes risk doubled in hypertriglyceridemic women regardless of HDL-cholesterol. Trg/HDL-C>2 in men and Trg>1.7 mmol/L in women were best predictors of diabetes. C3>1.3 g/L served additively in women alone. Regarding CHD risk, not CRP, but C3 contributed independently to Trg/HDL>2 in men [RR 2.46 (95% CI 1.33; 4.53)]; a high ratio was merely additive to elevated CRP in women. Among five cut-off values, predictive values for diabetes were highest for CRP >2.5 mg/L in men, Trg>1.7 mmol/L and C3>1.3 g/dL in women. Conclusion: Trg/HDL-C ratio >2 and/or CRP >2.5 mg/L in men and Trg>1.7 mmol/L+C3>1.3 g/dL in women are most appropriate markers regarding impaired antiinflammatory or atheroprotective HDL function. In normotriglyceridemic men with normal HDL-cholesterol levels, diabetes risk may be elevated due to presumably dysfunctional apolipoprotein A-I. (Anadolu Kardiyol Derg 2012; 12: 628-36) Key words: Coronary heart disease, Cox proportional regression analysis, C-reactive protein, diabetes type-2, HDL dysfunction, triglycerides, sensitivity, specificity Original Investigation Özgün Araşt›rma 628ÖZET Amaç: Yüksek yoğunluklu lipoprotein (HDL) parçacıklarının fonksiyon bozukluğu, glikoz tolerans bozukluğuna yatkın kişilerde kardiyometabolik hastalık üretebildiğinden, klinik belirteçlerinin belirlenmesi gerekir. Çalışma dizaynı: Öne dönük popülasyona dayalı. Yöntem: Toplam 2725 yetişkin 7.3±3.0 yıllık takipte Cox regresyon analiziyle değerlendirildi. Başlangıçta ilgili olguların dışlanmasından sonra, ileride diyabet ve koroner kalp hastalığının gelişmesi bakımından, C-reaktif protein (CRP), kompleman C3 (C3), trigliseridler (Trg) ve HDL-kolesterolün öngörü değerleri incelendi. Bulgular: Diyabet riski açısından kadınlarda, aterojen dislipidemi dışında, artmış CRP ile bağıntılı yüksek-Trg/normal HDL-kolesterol kategorisi ilişki gösterdi. Normal trigliserid ve HDL-kolesterol seviyesine sahip erkekler, düşük HDL-kolesterollü erkeklere kıyasla, daha yüksek apolipoprotein A-I düzeyiyle birlikte yüksek diyabet riski sergiledi. Hipertrigliseridemili kadınlarda diyabet riski, HDL-kolesterol düzeylerine bakılmaksızın, ikiye katlandı. CRP >2.5 mg/L ölçütü her iki cinsiyette diyabeti anlamlı öngördü; am...

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“…Logistic regression analysis for prediction of incident stroke by sex-and age-adjusted body height age-adjusted body height taller women. C3 activation leads to production of chemoattractants and C3 and its cleavage products link lipoprotein metabolism to immunity (27). Genetic predisposition is a major determinant of height, yet rising stature across successive birth cohorts suggests that early life environment (in terms of nutrition, illness, socioeconomic status and psychosocial stress) also has an important impact (10).…”

Section: Gender Differencementioning

confidence: 99%

Short stature is an independent risk marker for mortality and incident coronary heart disease only in women: a structural relationship?

Onat¹,

Örnek²,

Can³

et al. 2012

Anadolu Kardiyol Derg

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Short stature is an independent risk marker for mortality and incident coronary heart disease only in women: a structural relationship?Kısa boy mortalite ve insidan koroner kalp hastalığı riskinin yalnızca kadınlarda bağımsız bir belirtecidir: Yapısal ilişki mi?Original Investigation Özgün Araşt›rma ABSTRACTObjective: We evaluated the associations of short stature with coronary heart disease (CHD) risk or overall mortality, which vary with sex and ethnicity/race. Methods: Such associations were studied prospectively at a mean 13.5-years' follow-up in a population-based sample of 3394 Turkish adults (mean age 44±11 years) using Cox proportional hazards models. Covariates of height were sought in sex-specific tertiles.Results: Height averaged 162.7±6.5 cm. Age-adjusted estimated marginal means for serum triglycerides, C-reactive protein and complement C3 in women (but not men) were significantly higher with decreasing height tertiles. In sex-and age-adjusted models, height was associated in men with neither incident CHD, nor death. In women, 1-SD increment (6.5 cm) in height only tended to marginal inverse association with CHD, but predicted significantly all-cause death (HR 0.83, 95% CI 0.59-0.98); HR attenuated only marginally after further adjustment for family income bracket, smoking status, alcohol usage, systolic blood pressure, serum high-density lipoprotein (HDL)-and non HDL-cholesterol. A threshold below 160 cm of female height doubled the adjusted risk of death compared to taller women. Conclusion: In contrast to men, short stature in Turkish women tends to be an independent risk marker for CHD, and height below 160 cm is a strong marker of death. Gender-specific early-life influences enhancing pro-inflammatory state may affect death and future CHD.

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Complement C3 and cleavage products in cardiometabolic risk

Cited by 106 publications

References 91 publications

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

Clinical biomarkers of high-density lipoprotein dysfunction among middle-aged Turks

Short stature is an independent risk marker for mortality and incident coronary heart disease only in women: a structural relationship?

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