γ′ Fibrinogen: Evaluation of a New Assay for Study of Associations with Cardiovascular Disease

Lovely, Rehana Sultana; Kazmierczak, Steven C.; Massaro, Joseph M.; D’Agostino, Ralph B.; O’Donnell, Christopher J.; Farrell, David H.

doi:10.1373/clinchem.2009.138347

Cited by 53 publications

(59 citation statements)

References 23 publications

(29 reference statements)

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“…The association between g9 fibrinogen and these CVD risk factors remained significant after adjustment for total fibrinogen and is also accompanied by an increase in the g9/total fibrinogen ratio, suggesting that these associations are not merely reflecting the association of the CVD risk factors with total fibrinogen and that they are likely independent relationships. These results are in agreement with the study of Lovely et al 32 who also found significant associations between g9 fibrinogen and BMI, (decreased) HDL cholesterol, diabetes, blood glucose, and gender in whites. In two other studies, g9 fibrinogen did not, however, differ between genders, 7,33 and while we and others 7,33 found no association between g9 fibrinogen and age, a positive association was found by another group.…”

Section: 15supporting

confidence: 93%

“…In two other studies, g9 fibrinogen did not, however, differ between genders, 7,33 and while we and others 7,33 found no association between g9 fibrinogen and age, a positive association was found by another group. 32 In this study population, total fibrinogen increased over 10-year age categories and in individuals with increased total cholesterol (.5.2 mmol/L) while no increase was observed for g9 fibrinogen, resulting in a decreased g9/total fibrinogen ratio. In hyperhomocysteinemic individuals, on the other hand, decreased g9 fibrinogen was observed with no change in total fibrinogen consequently also decreasing the g9/total fibrinogen ratio.…”

Section: 15mentioning

confidence: 56%

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Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

Pieters¹,

Kotzé²,

Jerling³

et al. 2013

Blood

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Key Points• This paper describes the effect of fibrinogen g9 on clot structure in plasma (previously shown in purified systems).• This paper also describes the respective roles of total fibrinogen, fibrinogen g9 concentration, and ratio on clot structure and lysis rates.Fibrinogen g9 is known to influence fibrin clot structure in purified experimental models, but little is known regarding its influence on clot structure in plasma. Furthermore, the environmental and biological factors that affect its concentration are poorly described. We analyzed fibrinogen g9, total fibrinogen concentration, and fibrin clot structure in 2010 apparently healthy black South Africans and related them to traditional cardiovascular disease (CVD) risk factors. Fibrinogen g9 generally increased with increasing fibrinogen concentration, but a decreased g9/total fibrinogen ratio was found at the highest total fibrinogen concentrations. Clot maximum absorbance increased with total fibrinogen and fibrinogen g9, but decreased with g'/total fibrinogen ratio. Clot lysis time showed a stronger relationship with fibrinogen g9 than with total fibrinogen, whereby increased fibrinogen g9 delayed clot lysis. CVD risk factors (excluding fibrinogen) explained 20% and 3%, respectively, of the variance in fibrinogen g9 and the g9/total fibrinogen ratio, with Creactive protein making the biggest contribution. More than 50% of the variance in fibrinogen g9 and g9/total fibrinogen ratio is explained by factors other than total fibrinogen or other traditional CVD risk factors. Our data show that fibrinogen g9 modulates plasma clot structure and fibrinolysis and is also influenced by factors other than fibrinogen. (Blood. 2013;121(16):3254-3260)

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Section: 15supporting

confidence: 93%

Section: 15mentioning

confidence: 56%

Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

Pieters¹,

Kotzé²,

Jerling³

et al. 2013

Blood

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“…Many studies have related high levels of fibrinogen with cardiovascular disease (Danesh et al 2005). A recent study suggests that fibrinogen gamma chain precursor is an excellent marker of cardiovascular risk (Lovely et al 2010). Interestingly, in this work, we have shown that fibrinogen gamma chain was strongly decreased with the VOO diet compared with the SO diet at 6 and 24 months, reinforcing again the beneficial effects of this type of fat in the prevention of cardiovascular diseases.…”

Section: Effects Of Dietary Oils On Coagulation and Hemostatic Processessupporting

confidence: 78%

Dietary oil modifies the plasma proteome during aging in the rat

Santos‐González

Pérez‐Jiménez

Navas

et al. 2011

AGE

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“…Urinary fragments of Fg␤ (ROC of 0.85) and Fg␣ chains (ROC of 0.74) were found to distinguish patients with malignant versus benign ovarian cancer 38 and plasma levels of Fg␥Ј chain (a splice variant of Fg␥ chain) associated with several traditional cardiovascular risk factors in Framingham Offspring cohort. 39 The current assay is a sandwich ELISA-based Luminex assay using 2 polyclonal antibodies against Fg protein; therefore, it will be interesting to use a more targeted approach such as liquid chromatography-multiple reaction monitoring/mass spectrometry to identify whether there is a predominant excretion of Fg␤ chain polypeptides in the urine after kidney injury that would correlate with the highest Fg␤ chain mRNA levels in the kidney.…”

Section: Discussionmentioning

confidence: 99%

Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury

Krishnamoorthy

Ajay

Hoffmann

et al. 2011

Blood

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Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)␣, Fg␤, and Fg␥ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fg␣ and Fg␥ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fg␤ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n ‫؍‬ 25) from healthy volunteers (n ‫؍‬ 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate IntroductionKidney disease is a major public health concern receiving increased global attention owing to the significantly increased prevalence and high mortality rates. 1,2 Renal ischemia/reperfusion (I/R) accounts for a significant number of acute kidney injury (AKI) cases in humans. Studies suggest that damage to the renal microvascular architecture and deterioration of the angiogenic response constitutes the early steps in the complex multiple pathways involved in both early and chronic ischemic renal injury. 3 Restoration of blood flow to the site of injured tissue is crucial for developing a successful repair response that involves the surviving dedifferentiated cells spreading over the denuded basement membrane, undergoing mitogenesis and ultimately redifferentiating to re-establish and restore functional integrity of the nephron. 4,5 Although these processes are well described at the pathologic level, very little is known about the cellular and molecular mechanisms of action of blood proteins within the kidney and their contribution to pathogenesis of renal disease.Fibrinogen (Fg), a 340-kDa dimeric blood protein, is made up of 2 sets of 3 different polypeptide chains, Fg␣, Fg␤, and Fg␥, that span a length of 50 kb on chromosome 4 in region q28. 6 Although the primary site for Fg synthesis is shown to be liver, extrahepatic synthesis of Fg by epithelial cells of intestine, 7 cervix, 8 and lung 9,10 has been reported, suggesting that it may function in other structural and functional capacities. Furthermore, endogenous expression of Fg␣ and Fg␤ chain mRNA has been shown in the normal rat kidneys, levels of which significantly increase at 2 hours after the onset of brain death injury, 11,12 potentially restoring hemostasis by supporting extracellular matrix and wound repair processes after injury. 12 In addition to its major role in blood clotting and circulation via interaction with platelets, 13 Fg has been recognized as an important regulator of inflammation, 14 wound ...

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γ′ Fibrinogen: Evaluation of a New Assay for Study of Associations with Cardiovascular Disease

Abstract: BACKGROUND:Studies of disease associations with ␥Ј fibrinogen, a newly emerging risk factor for cardiovascular disease, have been hampered by the lack of a standardized and well-characterized assay.

Cited by 53 publications

References 23 publications

Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

Dietary oil modifies the plasma proteome during aging in the rat

Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury

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