Nicotinic acid (NA) regresses atherosclerosis in human imaging studies and reduces atherosclerosis in mice, mediated by myeloid cells, independent of lipoproteins. Since GPR109A is expressed by human monocytes, we hypothesized that NA may drive cholesterol efflux from foam cells. In THP-1 cells NA suppressed LPS-induced mRNA transcription of MCP-1 by 76.6±12.2% (P<0.01) and TNFα by 56.1±11.5% (P<0.01), yet restored LPS-induced suppression of PPARγ transcription by 536.5±46.4% (P<0.001) and its downstream effector CD36 by 116.8±19.8% (P<0.01). Whilst direct PPARγ-agonism promoted cholesterol efflux from THP-1 derived foam cells by 37.7±3.1% (P<0.01) and stimulated transcription of LXRα by 87.9±9.5% (P<0.001) and ABCG1 by 101.2±15.5% (P<0.01), NA showed no effect in foam cells on either cholesterol efflux or key RCT genes transcription. Upon foam cell induction, NA lost its effect on PPARγ and cAMP pathways, since its receptor, GPR109A, was down-regulated by foam cell transformation. This observation was confirmed in explanted human carotid plaques. In conclusion, despite NA's anti-inflammatory effect on human macrophages, it has no effect on foam cells in reverse cholesterol transport; due to GPR109A down-regulation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642175 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062934 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Comparison of the Inhibitory Effects of Flunixin Meglumine and Meloxicam on the Smooth Muscles Motility of the Gastrointestinal Tract of Cattle.
Vet Med Sci
January 2025
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ondokuz Mayis University, Samsun, Türkiye.
This study aimed to compare the inhibitory effect of flunixin meglumine and meloxicam on the smooth muscles of the gastrointestinal tract in male cattle. Tissue samples, including the abomasum, ileum, proximal loop and centripetal gyri of the ascending colon, were collected from routinely slaughtered male cattle. These samples were sectioned into strips and mounted in an isolated tissue bath system.
View Article and Find Full Text PDFEffect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.
J Neurochem
January 2025
The Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.
View Article and Find Full Text PDFThe positive feedback loop between SP1 and MAP2K2 significantly drives resistance to VEGFR inhibitors in clear cell renal cell carcinoma.
Int J Biol Sci
January 2025
Department of Urology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
Clear cell renal cell carcinoma (ccRCC) is one of the most common and aggressive malignancies of the urinary system. Despite being the first-line treatment for advanced ccRCC, vascular endothelial growth factor receptor inhibitors (VEGFRis) face significant limitations due to both initial and acquired resistance, which impede complete tumor eradication. Using a CRISPR/Cas9 library screening approach, was identified as a resistance-associated gene for three prevalent VEGFRis (Sunitinib, Axitinib, and Sorafenib).
View Article and Find Full Text PDFCold atmospheric plasma potentiates ferroptosis via EGFR(Y1068)-mediated dual axes on GPX4 among triple negative breast cancer cells.
Int J Biol Sci
January 2025
Tianjin Key Laboratory of Acute Abdomen Disease-Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, 8 Changjiang Avenue, Tianjin 300100, China.
Cold atmospheric plasma (CAP) has been proposed as an emerging onco-therapeutics that can specifically kill cancer cells without harming healthy cells. Here we explore its potency in triggering ferroptosis in transformed cells using triple negative breast cancer as the disease model. Through the whole transcriptome sequencing, mass spectrometry analysis, point mutation, and a series of and molecular assays, we identified two signaling axes centered at EGFR(Y1068), i.
View Article and Find Full Text PDFInclusion Complex of Nimodipine with Sulfobutylether-β-cyclodextrin: Preparation, Characterization, In Vitro and In Vivo Evaluation.
AAPS PharmSciTech
January 2025
Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, China.
Nimodipine (NIMO) is used to treat ischemic nerve injury from subarachnoid hemorrhage (SAH), but its low aqueous solubility limits clinical safety and bioavailability. This study aims to improve NIMO's solubility by preparing inclusion complexes with sulfobutylether-β-cyclodextrin (SBE-β-CD), reducing the limitations of Nimotop injection, including vascular irritation, toxicity, and poor dilution stability. The NIMO-SBE-β-CD inclusion complex (NIMO-CD) was characterized in both liquid and solid states through phase solubility studies and methods including DSC, FT-IR, XRD, and SEM.
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!