Background: Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality.
Methods: A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL and HDL that were also utilized to measure cholesterol efflux from macrophages.
Results: Among 45 quantified proteins, 13 in HDL and 33 in HDL were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL and HDL, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use.
Conclusion: HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.
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http://dx.doi.org/10.1186/s13098-023-01007-y | DOI Listing |
Free Radic Res
January 2025
Department of Biochemistry, Faculty of Medicine, Marmara University, 34854, Istanbul, Turkiye.
Naturally occurring vitamin E is a lipophilic plant-derived molecule corresponding to the 2R forms of alpha-tocopherol. A series of natural analogs or tocochromanols are present in nature, including β-, γ- and δ-tocopherol (βT, γT, δT), the corresponding tocotrienols (αTE, βTE, γTE, δTE) and tocomonoenols. Differences between these analogs as lipophilic antioxidants and modulators of molecular processes suggest specific therapeutic properties against various disorders associated with acute and chronic inflammation.
View Article and Find Full Text PDFGenet Epidemiol
January 2025
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).
View Article and Find Full Text PDFFront Microbiol
December 2024
Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia.
Introduction: Lactic acid bacteria are prized for their probiotic benefits and gut health improvements. This study assessed five LAB isolates from Neera, with RAMULAB51 (, GenBank ON171686.1) standing out for its high hydrophobicity, auto-aggregation, antimicrobial activity, and enzyme inhibition.
View Article and Find Full Text PDFBackground: The activation of brown adipose tissue (BAT) is associated with improved metabolic health in humans. We previously identified the mitochondrial protein 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) as a novel regulatory factor that integrates with lipid metabolism and is critical to sustain the long-term activation of BAT, but the precise mechanism and function of Nipsnap1 is unknown.
Objectives: Define how the regulatory factor Nipsnap1 integrates with lipid metabolism.
B7-H3 (CD276), a member of the B7-family of immune checkpoint proteins, has been shown to have immunological and non-immunological effects promoting tumorigenesis [1, 2] and expression correlates with poor prognosis for many solid tumors, including cervical, ovarian and breast cancers [3-6]. We recently identified a tumor-cell autochthonous tumorigenic role for dimerization of the 4Ig isoform of B7-H3 (4Ig-B7-H3) [7], where 4Ig-B7-H3 dimerization activated tumor-intrinsic cellular proliferation and tumorigenesis pathways, providing a novel opportunity for therapeutic intervention. Herein, a live cell split-luciferase complementation strategy was used to visualize 4Ig-B7-H3 homodimerization in a high-throughput small molecule screen (HTS) to identify modulators of this protein-protein interaction (PPI).
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