AI Article Synopsis
- Elderly familial hypercholesterolemia (FH) patients usually face high risks of coronary heart disease (CHD), but a subset remains free of CHD, suggesting the existence of protective factors.
- A study analyzed gene expression in blood cells from elderly FH patients with and without CHD, aiming to uncover potential cardioprotective gene profiles.
- Results indicated that while no significant gene expression differences were found between the two FH groups after adjustments, certain genes related to lipid metabolism and immune response showed nominal differences, highlighting a less atherogenic profile in event-free individuals.
Article Abstract
Background And Aims: Elderly familial hypercholesterolemia (FH) patients are at high risk of coronary heart disease (CHD) due to high cholesterol burden and late onset of effective cholesterol-lowering therapies. A subset of these individuals remains free from any CHD event, indicating the potential presence of protective factors. Identifying possible cardioprotective gene expression profiles could contribute to our understanding of CHD prevention and future preventive treatment. Therefore, this study aimed to investigate gene expression profiles in elderly event-free FH patients.
Methods: Expression of 773 genes was analysed using the Nanostring Metabolic Pathways Panel, in peripheral blood mononuclear cells (PBMCs) from FH patients ≥65 years without CHD (FH event-free, n = 44) and with CHD (FH CHD, n = 39), and from healthy controls ≥70 years (n = 39).
Results: None of the genes were differentially expressed between FH patients with and without CHD after adjusting for multiple testing. However, at nominal p < 0.05, we found 36 (5%) differentially expressed genes (DEGs) between the two FH groups, mainly related to lipid metabolism (e.g. higher expression of ABCA1 and ABCG1 in FH event-free) and immune responses (e.g. lower expression of STAT1 and STAT3 in FH event-free). When comparing FH patients to controls, the event-free group had fewer DEGs than the CHD group; 147 (19%) and 219 (28%) DEGs, respectively.
Conclusions: Elderly event-free FH patients displayed a different PBMC gene expression profile compared to FH patients with CHD. Differences in gene expression compared to healthy controls were more pronounced in the CHD group, indicating a less atherogenic gene expression profile in event-free individuals. Overall, identification of cardioprotective factors could lead to future therapeutic targets.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.atherosclerosis.2024.117507 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Differential Expression of miR-26b-5p, EGR1, and STAT1 in Peripheral Blood of Schizophrenia Patients.
Psychiatry Clin Psychopharmacol
December 2024
The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Background: This study aimed to investigate miRNAs and upstream regulatory transcription factors involved in schizophrenia (SZ) pathogenesis.
Methods: Differential expression of miRNAs and genes in SZ patients was investigated utilizing the gene expression omnibus dataset, gene ontology annotations, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Real-time quantitative polymerase chain reaction experiments were conducted to validate the predictive screening of regulatory genes in peripheral blood samples from 20 SZ patients and 20 healthy controls.
Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA.
Viruses
December 2024
Department of Medicine & State Key Laboratory of Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China.
Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg- upon treatment and had greatly reduced cccDNA products) and four HBeAg- patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.
View Article and Find Full Text PDFPD1-Targeted Transgene Delivery to Treg Cells.
Viruses
December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated tumor-infiltrating T lymphocytes, including regulatory T cells that suppress immune responses via FOXP3 expression. We developed PD1-targeted LVs by incorporating the anti-PD1 nanobody nb102c3 into receptor-blinded measles virus H and VSV-G glycoproteins.
View Article and Find Full Text PDFPotyvirus-Based Vectors for Heterologous Gene Expression in Plants.
Viruses
December 2024
Department of Virus Ecology, Institute of Virology, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia.
Over the past two decades, plant viral vectors have emerged as a powerful tool for the production of recombinant proteins in plants. Among the different plant viruses engineered to carry foreign genes of interest in their genomes, potyviruses have gained attention due to their polyprotein expression strategy and broad host range. To date, at least eleven different species belonging to the genus have been used for heterologous gene expression in both their natural and experimental hosts.
View Article and Find Full Text PDFDHX15 and Rig-I Coordinate Apoptosis and Innate Immune Signaling by Antiviral RNase L.
Viruses
December 2024
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
During virus infection, the activation of the antiviral endoribonuclease, ribonuclease L (RNase L), by a unique ligand 2'-5'-oilgoadenylate (2-5A) causes the cleavage of single-stranded viral and cellular RNA targets, restricting protein synthesis, activating stress response pathways, and promoting cell death to establish broad antiviral effects. The immunostimulatory dsRNA cleavage products of RNase L activity (RL RNAs) recruit diverse dsRNA sensors to activate signaling pathways to amplify interferon (IFN) production and activate inflammasome, but the sensors that promote cell death are not known. In this study, we found that DEAH-box polypeptide 15 (DHX15) and retinoic acid-inducible gene I (Rig-I) are essential for apoptosis induced by RL RNAs and require mitochondrial antiviral signaling (MAVS), c-Jun amino terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) for caspase-3-mediated intrinsic apoptosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!