scholarly journals Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long H. Ngo ◽  
M. Austin Argentieri ◽  
Simon T. Dillon ◽  
Blake Victor Kent ◽  
Alka M. Kanaya ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Plasma Protein ◽  
Expression Profiles ◽  
South Asians ◽  
Predictive Biomarkers ◽  
Information Criteria ◽  
Blood Protein ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

AbstractBlood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.

Abstract 13047: Plasma Protein Expression and Incident Cvd, and the Role of Resilience: Results From the Mediators of Atherosclerosis in South Asians Living in America (masala) Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Long Ngo ◽  
Austin Argentieri ◽  
Simon Dillon ◽  
Alka M Kanaya ◽  
Alexandra Shields ◽  
...  
Keyword(s):  
Religious Coping ◽  
Immune Cell ◽  
South Asians ◽  
Information Criteria ◽  
Complement Factor ◽  
Plasma Samples ◽  
Factor B ◽  
Complement Factor B ◽  
Increased Risk ◽  
Negative Religious Coping

Introduction: Few proteomics studies have included non-white individuals, and none have explored the influence of resiliency resources on the association between proteins and cardiovascular disease (CVD). Religious and spiritual beliefs and practices are understudied resiliency resources that may attenuate the influence of proteins associated with increased risk of CVD. Methods: We conducted a nested case-control study using data from the MASALA Study. We used baseline plasma samples from 50 South Asian participants with incident CVD and 50 sex- and age-matched controls. We analyzed plasma samples by SOMAscan, an aptamer-based proteomics platform, for 1305 unique proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates. We assessed the influence of measures of spiritual practices on the association between proteins and incident CVD events. Results: We identified 36 proteins that were significantly dysregulated among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5, Low affinity immunoglobulin gamma Fc region receptor II-a, Complement factor B) associated with CVD after adjustment for diabetes (c-statistic=0.82). Negative religious coping significantly modified the effect of Contactin-5 and Complement factor B for risk of CVD. ( Table ) Conclusions: Three novel plasma proteins were associated with incident CVD, and negative religious coping significantly modified the effect, in this pilot study of South Asians. Further investigation is needed to understand proteomic profiles across diverse communities, and the role that resiliency resources in modifying the putative effect of proteomic signatures.

scholarly journals The effects of metal ions and temperature on the interaction of cobra venom factor and human complement factor B.

1986 ◽  
Vol 261 (24) ◽  
pp. 11038-11044 ◽  
Author(s):  
P Hensley ◽  
M C O'Keefe ◽  
C J Spangler ◽  
J C Osborne ◽  
C W Vogel
Keyword(s):  
Metal Ions ◽  
Cobra Venom ◽  
Complement Factor ◽  
Human Complement ◽  
Cobra Venom Factor ◽  
Factor B ◽  
Complement Factor B

C3 Glomerulonephritis Associated With Complement Factor B Mutation

2015 ◽  
Vol 65 (3) ◽  
pp. 520-521 ◽  
Author(s):  
Sanjeev Sethi ◽  
Richard J.H. Smith ◽  
John J. Dillon ◽  
Fernando C. Fervenza
Keyword(s):  
Complement Factor ◽  
C3 Glomerulonephritis ◽  
Factor B ◽  
Complement Factor B

scholarly journals The Association Between Complement Component 2/Complement Factor B Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

2012 ◽  
Vol 176 (5) ◽  
pp. 361-372 ◽  
Author(s):  
Ammarin Thakkinstian ◽  
Mark McEvoy ◽  
Usha Chakravarthy ◽  
Subhabrata Chakrabarti ◽  
Gareth J. McKay ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Meta Analysis ◽  
Complement Component ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B ◽  
Age Related

scholarly journals Interplay between complement factor B and Toll‐like receptors and its role in septic cardiomyopathy

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Lin Zou ◽  
Yan Li ◽  
Yan Feng ◽  
Ming Zhang ◽  
Chan Chen ◽  
...  
Keyword(s):  
Septic Cardiomyopathy ◽  
Complement Factor ◽  
Toll Like Receptors ◽  
Factor B ◽  
Complement Factor B

scholarly journals Isolation of Carp Complement Factor B and Formation of the C3-Convertase

10.5109/4570 ◽  
2004 ◽  
Vol 49 (1) ◽  
pp. 101-110
Author(s):  
Miki Nakao ◽  
Makiko Nakahara ◽  
Tomoki Yano
Keyword(s):  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

scholarly journals P0531CONTINUOUS HEMODIAFILTRATION WITH PMMA HEMOFILTER MODULATED COMPLEMENT ACTIVATION AND RENAL DYSFUNCTION IN A SWINE MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alessandra Stasi ◽  
ROSSANA FRANZIN ◽  
Fabio Sallustio ◽  
Chiara Divella ◽  
Claudia Curci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Complement Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Kidney Injury ◽  
Swine Model ◽  
Complement Factor ◽  
Factor B ◽  
Renal Biopsies

Abstract Background and Aims Sepsis-induced acute kidney injury (AKI) is a growing health care problem, refractory to conventional treatments. This disease is characterized by an overwhelmed immune response against a primary insult that become responsible for renal dysfunction and poor outcome. Therapeutic strategies based on blood purification have been developed for the treatment of this disease. The use of polymethyl methacrylate (PMMA) membrane hemofilter in continuous hemodiafiltration (CHDF) modality showed better hemodynamic stability and efficient renal support in chronic dialysis maintenance. Here we investigated the efficacy of Hemofeel PMMA membrane (TORAY, Japan) in interfering with Complement activation and renal damage in a swine model of sepsis-induced AKI. Method After 3 hours from LPS infusion, 7 hours of PMMA-CVVH treatment or 7 hours of polysulfone (PSF)-CVVH were performed. Animals were sacrificed after 24h from LPS infusion. Histologic and renal function parameters were analyzed in all pigs. Pentraxin-3 (PTX3) and C5b-9 deposits were assessed on renal biopsies. Systemic Complement activation was evaluated by Wieslab kit. Gene expression profile was obtained from isolated PBMCs by Agilent SurePrint G3 Porcine Gene Expression Microarrays. Genespring and R software were used for the analysis. Results were validated by Real-time PCR. Results Analysis of renal biopsies from septic pigs presented increased interstitial leucocyte infiltrate, extensive collagen deposition and diffuse glomerular thrombi compared to healthy pigs (p<0.05). Confocal analysis showed extensive PTX-3 and C5-b9 deposits at tubulo-interstitial level associated with significant activation of systemic complement classical and alternative pathways (p<0.05). Interestingly, PMMA-CVVH treatment significantly reduced local and systemic complement activation, leucocyte infiltrate and tubule-interstitial fibrosis (p<0.05). On the contrary, no significant improvement was observed by PSF-CVVH treatment. Then, we compared the whole-genome gene expression profiles of swine PBMC. We identified 711 differentially expressed genes comparing PBMC before LPS infusion (LPS T0) and after 24 hours from LPS infusion (LPS T24) and 913 genes comparing gene expression profiles of LPS T24 group with that of septic pigs treated with PMMA-CVVH (PMMA T24 group) (fold change >2 ; false discovery rate <0.05). The most modulated genes were Granzime B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, SERPINB-1 and TIMP-2 that were closely related to sepsis-induced immunological process. Finally, quantitative PCR confirmed the microarray data indicating that Granzime B and Complement Factor B upregulation in PBMC was significantly hampered by PMMA treatment. Conclusion Our data suggest that LPS induced AKI is characterized by activation of Classical and alternative Complement pathways resulting in significant renal tissue damage. By interfering with complement activation and inflammatory response, PMMA membrane might prevent dysfunctional activation of resident renal cells with prevention of sepsis-induced AKI.

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