| 1. |
- Khan, Noman, et al.
(författare)
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Dysregulation of metalloproteins in ischemic heart disease patients with systolic dysfunction
- 2023
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 232
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Metalloproteins have been linked to human health and diseases. The molecular functions of metalloproteins in IHD is not well understood and require further exploration. The objective of this study was to find out the role of metalloproteins in the pericardial fluid of IHD patients having normal (EF > 45) and impaired (EF < 45) left ventricular ejection fraction (LVEF). IHD patients were grouped into two categories: LVEF<45 (n = 12) and LVEF >45 (n = 33). Pooled samples of pericardial fluid were fractionated by using ZOOM-isoelectric focusing (IEF) followed by further processing using one-dimensional gel electrophoresis (1D SDS-PAGE) and filter-aided sample preparation (FASP). Tryptic peptides of each fraction and differential bands were then analyzed by nano-LC-ESI-MS/MS. Protein identification was performed through a Mascot search engine using NCBI-Prot and SwissProt databases. A total of 1082 proteins including 154 metalloproteins were identified. In the differential bands, 60 metalloproteins were identified, while 115 metalloproteins were identified in all ZOOM-IEF fractions. Twelve differentially expressed metalloproteins were selected in the intense bands according to their molecular weight (MW) and isoelectric point (pI). The 12 differentially expressed metalloprotein includes ceruloplasmin, Prothrombin, Vitamin K-dependent protein, Fibulin-1, Ribosomal protein S6 kinase alpha-6, nidogen, partial, Serum albumin, Hemopexin, C-reactive protein, Serum amyloid P-component, and Intelectin-1 protein which were all up-regulated while serotransferrin is the only metalloprotein that was down-regulated in impaired (LVEF<45) group. Among the metalloproteins, Zn-binding proteins are 36.5 % followed by Ca-binging 32.2 %, and Fe-binging 12.2 %. KEGG, pathway analysis revealed the association of ceruloplasmin and serotransferrin with the ferroptosis pathway. In conclusion, 154 metalloproteins were identified of them the Zn-binding protein followed by Ca-binding and Fe-binding proteins were the most abundant metalloproteins. The two metalloproteins, the Cu-binding protein ceruloplasmin, and Fe-binding protein serotransferrin are involved in the ferroptosis pathway, an iron-dependent form of regulated cell death that has been linked to cardiac pathology, especially in IHD patients having impaired systolic (LVEF<45) dysfunction. However, further research is required to validate these findings.
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| 2. |
- Khan, Noman, et al.
(författare)
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Understanding of metals dysregulation in patients with systolic and diastolic dysfunction in ischemic heart disease
- 2020
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic heart disease (IHD) is the leading cause of death and chronic disability in the world. IHD affects both the systolic and diastolic function of the heart which progressively leads to heart failure; a structural and functional impairment of filling or ejection of blood from the heart. In this study, the progression of systolic and diastolic dysfunction characterized according to their echocardiographic parameters including left ventricular ejection fraction (EF), grades of diastolic dysfunction and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), were correlated with differential regulation of various metals in patients sera samples (n = 62) using inductive coupled plasma-mass spectrometry (ICP-MS). Chromium, nickel and selenium were found significant (p < 0.05) in patients having EF < 45% compared with EF > 45%. In patients with systolic dysfunction (EF < 45%), the level of selenium was decreased while the level of chromium and nickel was increased compared to patients with EF > 45%. Selenium level was also decreased significantly (p < 0.05) in grade 1A and 2 patients that are considered as higher grades of diastole dysfunction in comparison to grade 0-1. Overall, selenium deficiency was identified in both systolic and diastolic dysfunctions of IHD patients corresponding to the progression of disease that could be related to many metabolic and translational pathways specifically which involve selenoproteins.
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| 3. |
- Ullah, Junaid, et al.
(författare)
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Pericardial fluid proteomic label-free quantification of differentially expressed proteins in ischemic heart disease patients with systolic dysfunction by nano-LC-ESI-MS/MS analysis
- 2021
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:1, s. 320-327
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Tidskriftsartikel (refereegranskat)abstract
- Left ventricular systolic dysfunction (LVSD) is common in patients with pre-existing ischemic heart disease (IHD) and myocardial infarction. An untargeted proteomic approach is used to improve the understanding of the molecular mechanisms associated with LVSD and to find out potential proteomic signatures in pericardial fluid. The pericardial fluid of IHD (n = 45) patients was grouped into two categories according to the left ventricular ejection fraction, LVEF ≥45 (n = 33) and LVEF <45 (n = 12), and analyzed by using nano-liquid chromatography–mass spectrometry (nano-LC-MS/MS) technique. The nano-LC-MS/MS analysis resulted in the identification of 709 pericardial fluid (PF) proteins in both normal and impaired systolic functional groups (LVEF ≥45 vs. LVEF <45). Sixteen proteins were found to be differentially expressed (p < 0.05, fold change >2) including 12 down-regulated and 4 up-regulated in the impaired systolic functional group (LVEF <45) compared to the normal group (LVEF ≥45). Among the differentially expressed proteins the inflammatory marker albumin, atherosclerosis marker apolipoprotein A-IV and hedgehog-interacting protein marker of angiogenesis were predominantly associated with the impaired LVEF <45 group. KEGG pathway analysis revealed that the hedgehog (Hh) signalling pathway is up-regulated in LVSD reflecting the underlying molecular and pathophysiological processes.
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