PPBP gene as a biomarker for coronary heart disease risk in postmenopausal Thai women

Abstract

Background Estrogen is an important ovarian hormone with anti-atherogenic and cardioprotective effects. Postmenopausal women have lower estrogen levels, associated with significantly higher risks of coronary heart disease (CHD) and CHD-related death. Effective biomarkers for the diagnosis, prediction, and treatment of CHD are needed to address this problem and thus reduce the mortality due to CHD in postmenopausal women. We recently reported that the PPBP and DEFA1/DEFA3 genes may be feasible synergistic biomarkers for CHD risk in Thai men with hyperlipidemia. The PPBP gene encodes pro-platelet basic protein (PPBP) from activated platelets, and DEFA1/DEFA3 encodes human neutrophil peptides (HNP) 1–3, mainly produced by activated neutrophils. Both platelets and neutrophils are involved in chronic inflammation during the development of atherogenesis and CHD. This study investigated the potential roles of PPBP and DEFA1/DEFA3 and their proteins as biomarkers for CHD risk in postmenopausal Thai women. Methods This cross-sectional study enrolled 90 postmenopausal Thai women, including 12 healthy controls (N), 18 patients with hyperlipidemia (H), and 21 patients diagnosed with CHD. The remaining 39 women were receiving cholesterol-lowering drugs for hyperlipidemia (HD) were excluded from the study. All CHD patients underwent coronary bypass grafting or coronary angioplasty. PPBP and DEFA1/DEFA3 mRNA expression levels in peripheral blood mononuclear cells isolated from heparinized blood were determined by quantitative reverse-transcription polymerase chain reaction. Levels of PPBP and HNP-1–3 proteins in corresponding plasma samples were assessed by enzyme-linked immunosorbent assay. Differences in parameters were compared among groups and correlations between parameters and clinical manifestations were analyzed. Results PPBP mRNA and protein levels were significantly increased in the CHD group compared with the N and H groups. In contrast, DEFA1/DEFA3 mRNA and HNP-1–3 protein levels did not differ significantly among the groups. None of the levels were associated with any of the clinical parameters analyzed in this study. Conclusion The results indicate that gene and protein expression levels of PPBP, but not DEFA1/DEFA3, and HNP-1–3, may be feasible biomarkers for assessing CHD risk in postmenopausal Thai women with hyperlipidemia.

The expression levels of chemotaxis-related molecules CXC chemokine receptor 1, interleukin-8, and pro-platelet basic protein in gingival tissues

“…The results showed that both the mRNA and protein of PPBP were significantly higher in inflammatory gingival tissues in comparison to healthy controls. High expression of PPBP was found in the plasma or serum of various inflammatory, allergy, and cardiovascular disorders, 15 , 16 , 17 , 19 which raises the possibility that PPBP contributes to the host immune response. However, the relationship between PPBP and periodontitis is still unclear.…”

“…They reported that PPBP is specifically elevated in the serum of Porphyromonas gingivalis -infected mice compared with sham-infected mice. 25 PPBP has been found in the plasma of people with diabetes mellitus, 15 coronary artery disease, 19 and the serum of people with rheumatoid arthriti. 17 It is believed to be a possible biomarker for these diseases.…”

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…Recent studies have shown that altered expression of DDX58 [413], STAT1 [414], TLR4 [415], CYP2D6 [416], JAK2 [417], TLR2 [418], DUSP6 [419], HDAC9 [420], LATS2 [421], CA2 [150], HIPK3 [422], CCR2 [423], GAB1 [120], UFL1 [424], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [425], PRKAR1A [265], SIRT1 [426], FGL2 [427], TET2 [428], ASCC2 [429], BIN1 [430], HSPB1 [431], IGFBP4 [432], TRPM4 [433] and LGALS3 [434] might be associated with the progression of heart failure. STAT1 [435], TLR4 [436], ABCA1 [437], PTGS2 [68], CYP2D6 [438], CR1 [439], PDK4 [440], RNF213 [441], ZDHHC17 [70], TLR8 [442], PDGFC (platelet derived growth factor C) [443], TLR2 [444], CYP1B1 [445], HDAC9 [446], IL1RN [447], GCH1 [448], EGR1 [449], ZEB2 [450], PLA2G7 [451], CCR2 [452], GCLC (glutamate-cysteine ligase catalytic subunit) [258], VEGFA (vascular endothelial growth factor A) [453], CD46 [454], NFKBIZ (NFKB inhibitor zeta) [455], LDLR (low density lipoprotein receptor) [456], TLR6 [457], SIRT1 [458], NOD2 [459], FGL2 [460], IDH1 [461], TET2 [462], PFKFB2 [463], KDM6A [464], IKZF2 [465], ZNF606 [466], PF4 [467], CCR7 [468], RUNX3 [469], TCF7 [470], PPBP (pro-platelet basic protein) [471], IGFBP4 [280], HSPG2 [472] and LGALS3 [236] expression might be regarded as an indicator of susceptibility to CAD. STAT1 [473], TLR4 [367], JAK2 [474], PDGFC (platelet derived growth factor C) […”

Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19

“…CCC analysis further indicated the presence of a representative CXCL signaling pathway (i.e., the L–R pair of PPBP and CXCR2) in the C4_DEFA1/1B/3 population. The PPBP ligand, one of the signatures of the C4_DEFA1/1B/3 subtype in this study, is involved in various conditions; PPBP was detected in activated platelets that are involved in chronic inflammation during the development of atherogenesis and coronary heart disease (CHD), and thus could be used as a biomarker for CHD risk in postmenopausal Thai women [51]. Combined with PADI4 expression, PPBP expression may be considered a non-invasive multi-marker approach offering diagnostic and clinical value in patients with suspected lung cancer [51].…”

“…The PPBP ligand, one of the signatures of the C4_DEFA1/1B/3 subtype in this study, is involved in various conditions; PPBP was detected in activated platelets that are involved in chronic inflammation during the development of atherogenesis and coronary heart disease (CHD), and thus could be used as a biomarker for CHD risk in postmenopausal Thai women [51]. Combined with PADI4 expression, PPBP expression may be considered a non-invasive multi-marker approach offering diagnostic and clinical value in patients with suspected lung cancer [51]. Another study demonstrated that PPBP is a major repressive target of glucocorticoids that promote gluconeogenesis [52,53].…”