scholarly journals NFkB Inhibition Mitigates Serum Amyloid A-Induced Pro-Atherogenic Responses in Endothelial Cells and Leukocyte Adhesion and Adverse Changes to Endothelium Function in Isolated Aorta

2018 ◽  
Author(s):  
Abigail Vallejo ◽  
Belal Chami ◽  
Joanne M. Dennis ◽  
Martin Simone ◽  
Gulfam Ahmad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Vascular Function ◽  
Serum Amyloid A ◽  
Ex Vivo ◽  
Early Stage ◽  
Leukocyte Adhesion ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Isolated Aorta

The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFkB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFkB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 µM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and TNF increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and IL-6 protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cGMP content. Together these data suggest that inhibition of NFkB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.

scholarly journals NFκB Inhibition Mitigates Serum Amyloid A-Induced Pro-Atherogenic Responses in Endothelial Cells and Leukocyte Adhesion and Adverse Changes to Endothelium Function in Isolated Aorta

2018 ◽  
Vol 20 (1) ◽  
pp. 105
Author(s):  
Abigail Vallejo ◽  
Belal Chami ◽  
Joanne Dennis ◽  
Martin Simone ◽  
Gulfam Ahmad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Vascular Function ◽  
Serum Amyloid A ◽  
Ex Vivo ◽  
Early Stage ◽  
Leukocyte Adhesion ◽  
Serum Amyloid ◽  
Guanosine Monophosphate ◽  
Amyloid A

The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFκB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFκB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 μM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and Tumor Necrosis Factor (TNF) increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and interleukin 6 (IL-6) protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cyclic guanosine monophosphate (cGMP) content. Together these data suggest that inhibition of NFκB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.

Serum amyloid A activation of human coronary artery endothelial cells exhibits a neutrophil promoting molecular profile

2013 ◽  
Vol 90 ◽  
pp. 55-63 ◽  
Author(s):  
Katja Lakota ◽  
Katjusa Mrak-Poljsak ◽  
Borut Bozic ◽  
Matija Tomsic ◽  
Snezna Sodin-Semrl
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Molecular Profile ◽  
Human Coronary Artery ◽  
Amyloid A

scholarly journals Serum concentrations and expressions of serum amyloid A and leptin in adipose tissue are interrelated: the Genobin Study

2008 ◽  
Vol 158 (3) ◽  
pp. 333-341 ◽  
Author(s):  
T Lappalainen ◽  
M Kolehmainen ◽  
U Schwab ◽  
L Pulkkinen ◽  
D E Laaksonen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Weight Reduction ◽  
Serum Amyloid A ◽  
Normal Weight ◽  
Serum Amyloid ◽  
Serum Concentrations ◽  
Amyloid A ◽  
Obese Subjects

ObjectiveSerum amyloid A (SAA) is a novel link between increased adipose tissue mass and low-grade inflammation in obesity. Little is known about the factors regulating its serum concentration and mRNA levels. We investigated the association between SAA and leptin in obese and normal weight subjects and analyzed the effect of weight reduction on serum SAA concentration and gene expression in adipose tissue of the obese subjects.MethodsSeventy-five obese subjects (60±7 years, body mass index (BMI) 32.9±2.8 kg/m2, mean±s.d.) with impaired fasting plasma glucose or impaired glucose tolerance and other features of metabolic syndrome, and 11 normal weight control subjects (48±9 years, BMI 23.7±1.9 kg/m2) were studied at the baseline. Twenty-eight obese subjects underwent a 12-week intensive weight reduction program followed by 5 months of weight maintenance. Blood samples and abdominal s.c. adipose tissue biopsies were taken at the baseline and after the follow-up. Gene expression was studied using real-time quantitative PCR.ResultsThe gene expressions in women and serum concentrations of leptin and SAA were interrelated independently of body fat mass in the obese subjects (r=0.54, P=0.001; r=0.24, P=0.039 respectively). In multiple linear regression analyses, leptin mRNA explained 38% of the variance in SAA mRNA (P=0.002) in the obese women. Weight loss of at least 5% increased SAA mRNA expression by 48 and 36% in men and women, but serum SAA concentrations did not change.ConclusionsThe association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome.

scholarly journals Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells

2008 ◽  
Vol 295 (6) ◽  
pp. H2399-H2408 ◽  
Author(s):  
Xinwen Wang ◽  
Hong Chai ◽  
Zehao Wang ◽  
Peter H. Lin ◽  
Qizhi Yao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Coronary Arteries ◽  
Molecular Mechanisms ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Dependent Manner ◽  
Amyloid A ◽  
Enos Mrna

The objective of this study was to determine the effects and mechanisms of serum amyloid A (SAA) on coronary endothelial function. Porcine coronary arteries and human coronary arterial endothelial cells (HCAECs) were treated with SAA (0, 1, 10, or 25 μg/ml). Vasomotor reactivity was studied using a myograph tension system. SAA significantly reduced endothelium-dependent vasorelaxation of porcine coronary arteries in response to bradykinin in a concentration-dependent manner. SAA significantly decreased endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein levels as well as NO bioavailability, whereas it increased ROS in both artery rings and HCAECs. In addition, the activities of internal antioxidant enzymes catalase and SOD were decreased in SAA-treated HCAECs. Bio-plex immunoassay analysis showed the activation of JNK, ERK2, and IκB-α after SAA treatment. Consequently, the antioxidants seleno-l-methionine and Mn(III) tetrakis-(4-benzoic acid)porphyrin and specific inhibitors for JNK and ERK1/2 effectively blocked the SAA-induced eNOS mRNA decrease and SAA-induced decrease in endothelium-dependent vasorelaxation in porcine coronary arteries. Thus, SAA at clinically relevant concentrations causes endothelial dysfunction in both porcine coronary arteries and HCAECs through molecular mechanisms involving eNOS downregulation, oxidative stress, and activation of JNK and ERK1/2 as well as NF-κB. These findings suggest that SAA may contribute to the progress of coronary artery disease.

scholarly journals Ex Vivo and In Vitro Effect of Serum Amyloid A in the Induction of Macrophage M2 Markers and Efferocytosis of Apoptotic Neutrophils

2015 ◽  
Vol 194 (10) ◽  
pp. 4891-4900 ◽  
Author(s):  
Lei Sun ◽  
Huibin Zhou ◽  
Ziyan Zhu ◽  
Qian Yan ◽  
Lili Wang ◽  
...  
Keyword(s):  
Serum Amyloid A ◽  
Ex Vivo ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Vitro Effect

scholarly journals Colocalization of Serum Amyloid A with Microtubules in Human Coronary Artery Endothelial Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Katja Lakota ◽  
Nataša Resnik ◽  
Katjuša Mrak-Poljšak ◽  
Snežna Sodin-Šemrl ◽  
Peter Veranič
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Actin Filaments ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Mrna Levels ◽  
Human Coronary Artery ◽  
Double Labeling ◽  
Amyloid A ◽  
Cytoskeletal Elements

Serum amyloid A (SAA) acts as a major acute phase protein and represents a sensitive and accurate marker of inflammation. Besides its hepatic origin, as the main source of serum SAA, this protein is also produced extrahepatically. The mRNA levels of SAA become significantly elevated following proinflammatory stimuli, as well as, are induced through their own positive feedback in human primary coronary artery endothelial cells. However, the intracellular functions of SAA are so far unknown. Colocalization of SAA with cytoskeletal filaments has previously been proposed, so we analyzed the colocalization of SAA with all three cytoskeletal elements: actin filaments, vimentin filaments, and microtubules. Immunofluorescent double-labeling analyses confirmed by PLA method revealed a strict colocalization of SAA with microtubules and a very infrequent attachment to vimentin while the distribution of actin filaments appeared clearly separated from SAA staining. Also, no significant colocalization was found between SAA and endomembranes labeled with the fluorescent lipid stain DiO6. However, SAA appears to be located also unbound in the cytosol, as well as inside the nucleus and within nanotubes extending from the cells or bridging neighboring cells. These different locations of SAA in endothelial cells strongly indicate multiple potential functions of this protein.

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