PR3 levels are impaired in plasma and PBMCs from Arabs with cardiovascular diseases


Autoři: Abdelkrim Khadir aff001;  Dhanya Madhu aff001;  Sina Kavalakatt aff001;  Preethi Cherian aff001;  Monira Alarouj aff002;  Abdullah Bennakhi aff002;  Jehad Abubaker aff001;  Ali Tiss aff001;  Naser Elkum aff003
Působiště autorů: Biochemistry and Molecular Biology Department, Research Division, Dasman Diabetes Institute, Kuwait City, Kuwait aff001;  Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait aff002;  Sidra Medicine, Doha, Qatar aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227606

Souhrn

Cardiovascular disease (CVD) risks persist in patients despite treatment. CVD susceptibility also varies with sex and ethnicity and is not entirely explained by conventional CVD risk factors. The aim of the present study was to identify novel CVD candidate markers in circulating Peripheral blood mononuclear cells (PBMCs) and plasma from Arab obese subjects with and without CVD using proteomic approaches. Human adults with confirmed CVD (n = 208) and matched non-CVD controls (n = 152) living in Kuwait were examined in the present cross-sectional study. Anthropometric and classical biochemical parameters were determined. We employed a shotgun proteomic profiling approach on PBMCs isolated from a subset of the groups (n = 4, each), and differentially expressed proteins selected between the two groups were validated at the mRNA level using RT-PCR (n = 6, each). Plasma levels of selected proteins from the proteomics profiling: Proteinase-3 (PR3), Annexin-A3 (ANX3), Defensin (DEFA1), and Matrix Metalloproteinase-9 (MMP9), were measured in the entire cohort using human enzyme-linked immunosorbent assay kits and were subsequently correlated with various clinical parameters. Out of the 1407 we identified and quantified from the proteomics profiling, 47 proteins were dysregulated with at least twofold change between the two subject groups. Among the differentially expressed proteins, 11 were confirmed at the mRNA levels. CVD influenced the levels of the shortlisted proteins (MMP9, PR3, ANX3, and DEFA1) in the PBMCs and plasma differentially. Despite the decreased levels of both protein and mRNA in PBMCs, PR3 circulating levels increased significantly in patients with CVD and were influenced by neither diabetes nor statin treatment. No significant changes were; however, observed in the DEFA1, MMP9, and ANX3 levels in plasma. Multivariate logistic regression analysis revealed that only PR3 was independently associated with CVD. Our results suggest that the dysregulation of PR3 levels in plasma and PBMCs reflects underlying residual CVD risks even in the treated population. More prospective and larger studies are required to establish the role of PR3 in CVD progression.

Klíčová slova:

Biomarkers – Blood plasma – Cardiovascular diseases – Diabetes mellitus – Gene expression – Protein expression – Statins – Defensins


Zdroje

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