Abstract 5542: Role of Scavenger Receptor BI in Sepsis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ling Guo ◽  
Eric Smart ◽  
Xiangan Li
Keyword(s):  
Animal Model ◽  
American Heart Association ◽  
American Heart ◽  
Scavenger Receptor ◽  
Cecal Ligation ◽  
Heart Association ◽  
Wild Type ◽  
Scavenger Receptor Bi ◽  
Lps Challenge

Scavenger receptor BI (SR-BI) is a well-established HDL receptor that regulates plasma HDL cholesterol levels by selectively uptake cholesterol ester from HDL. We recently reported a novel function of SR-BI namely protection against endotoxin-induced animal death. Using a lipopolysaccharides (LPS) induced endotoxic animal model, we found that LPS challenge induced 90% fatality of SR-BI null mice while all the wild type littermates survived, indicating that SR-BI plays a pivotal role in protection against LPS toxicity in vivo. In the current studies, we determined whether SR-BI plays a protective role in sepsis using an established septic animal model (cecal ligation and puncture, CLP). We demonstrate that CLP treatment induced 100% fatality of SR-BI null mice (n=20) whereas only 21% fatality of wild type littermates (n=27) and 36% fatality of heterozygous littermates (n=30). Moreover, SR-BI null mice exhibited exaggerated and prolonged inflammatory response as shown by elevated proinflammatory cytokine levels in serum upon CLP treatment compared to wild type littermates. Further studies revealed that the plasma LPS levels were significantly higher in SR-BI null mice compared to wild type control mice, indicating that SR-BI is required for LPS clearance in sepsis. Our findings clearly demonstrate that SR-BI is a critical protective modulator in sepsis in mice, which may reveal a novel target for the intervention of sepsis. (Supported by grant from American Heart Association 0530241N) This research has received full or partial funding support from the American Heart Association, AHA National Center.

Abstract 3729: Scavenger Receptor Bi (sr-bi)-mediated Selective Uptake Is Required For The Remodelling Of Hdl By Endothelial Lipase

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Niels Nijstad ◽  
Harmen Wiersma ◽  
Thomas Gautier ◽  
Markus van der Giet ◽  
Cyrille Maugeais ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Plasma Levels ◽  
Scavenger Receptor ◽  
Negative Regulator ◽  
Whole Body ◽  
Endothelial Lipase ◽  
Wild Type ◽  
Selective Uptake ◽  
Scavenger Receptor Bi

Objectives Endothelial lipase (EL) is a negative regulator of HDL cholesterol plasma levels, and scavenger receptor BI (SR-BI) is involved in remodelling of HDL. The present study investigates the requirement of SR-BI for the effects of EL-mediated phospholipid hydrolysis on HDL metabolism in vivo . Methods and Results In vitro , selective uptake from EL-modified HDL was 129 % higher than selective uptake from control HDL in SR-BI overexpressing cells (p=0.01). In vivo overexpression of human EL by means of recombinant adenovirus decreased HDL plasma levels significantly (p<0.01). FPLC analysis and non-denaturing gel electrophoresis revealed that EL expression resulted in the generation of small HDL particles in wild-type mice, while in SR-BI −/− mice small HDL were preferentially removed. In kinetic experiments the fractional catabolic rate (FCR) of HDL cholesteryl ester (CE) increased by 110% (p<0.001) and the FCR of HDL apolipoproteins by 64% (p<0.001) in response to EL overexpression in wild-type mice. In SR-BI −/− mice a similar increase in the HDL apolipoprotein FCR occurred (p<0.001), however, no further increase in HDL CE catabolism. The apparent whole body selective uptake was increased 3-fold by EL in wild-type mice (p<0.001), while there was no selective uptake in SR-BI ko mice. EL overexpression increased hepatic selective uptake as well as holoparticle uptake (each p<0.01) in wild-type mice, while in SR-BI ko mice only holoparticle uptake increased (p<0.01). Conclusions Our results indicate that SR-BI-mediated selective uptake of HDL cholesteryl ester is essential for the remodelling of large alpha-migrating HDL particles by EL.

scholarly journals Diagnosis and Management of Myocarditis in Children: A Scientific Statement From the American Heart Association

Circulation ◽  
2021 ◽  
Author(s):  
Yuk M. Law ◽  
Ashwin K. Lal ◽  
Sharon Chen ◽  
Daniela Čiháková ◽  
Leslie T. Cooper ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Endomyocardial Biopsy ◽  
American Heart Association ◽  
American Heart ◽  
Current Knowledge ◽  
Heart Association ◽  
Circulatory Support

Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.

Evidenzbasierte Indikationen zur chirurgischen Therapie extrakranieller Karotisstenosen

2003 ◽  
Vol 22 (05) ◽  
pp. 222-232
Author(s):  
H.-H. Eckstein
Keyword(s):  
American Heart Association ◽  
American Heart ◽  
Heart Association ◽  
Amaurosis Fugax

ZusammenfassungNach Durchführung prospektiv-randomisierter Studien liegen für die Karotis-Thrombendarteriektomie (KarotisTEA) höhergradiger Karotisstenosen gesicherte Indikationen auf dem Evidenzlevel Ia mit dem Empfehlungsgrad A vor. Dies betrifft sowohl >50%ige symptomatische als auch >60%ige asymptomatische Stenosen (NASCET-Kriterien). In Subgruppen-Analysen aus NASCET konnten klinische und morphologische Variablen identifiziert werden, die auf ein besonders hohes Risiko eines karotisbedingten Schlaganfalls im natürlichen Verlauf hinweisen. Patienten mit folgenden Variablen profitieren daher besonders von der Karotis-TEA: Stenosegrad >90%, schlechter Kollateralkreislauf, kontralateraler Karotisverschluss, Plaque-Ulzerationen, Tandemstenosen, intraluminale Thromben, nicht-lakunärer Hirninfarkt, Lebensalter >75 Jahre, komplexes klinisches Risikoprofil, Hemisphären-TIA (vs. Amaurosis fugax), männliches Geschlecht. Der präventive Effekt der Karotis-TEA kann jedoch nur unter Beachtung eines niedrigen perioperativen Schlaganfallbzw. Letalitätrisikos realisiert werden. Nach Empfehlungen der American Heart Association (AHA) darf das perioperative Risiko 3% bei asymptomatischen Stenosen ohne kontralaterale Stenose, 5% bei asymptomatischen Stenosen mit hochgradiger kontralateraler Stenose oder Verschluss und 6% bei symptomatischen >50%ige Stenosen (NASCET-Kriterien) nicht überschreiten. Die Ergebnisse der Qualitätssicherung Karotis-TEA der Deutschen Gesellschaft für Gefäßchirurgie (DGG) zeigen, dass diese maximal akzeptablen Obergrenzen zum Teil deutlich unterschritten werden. Vor diesem Hintergrund stellt das Stenting von Karotisstenosen einen klinischen Heilversuch dar, der nur nach interdisziplinärem Konsil und/oder i. R. randomisierter Studien zulässig ist.

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