Background: Homocysteine, a risk factor for atherosclerosis, increases intimal hyperplasia after carotid endarterectomy with associated smooth muscle cell proliferation and modulation of cytokines. The N-methyl-D-aspartate receptor (NMDAr), a glutamate-gated ion channel receptor, is associated with homocysteine-induced cerebrovascular injury; however, the receptor has not been identified in peripheral vascular cells, nor has any interaction with homocysteine been clarified. Our objectives were first, to identify NMDAr in rat carotid artery and rat aorta endothelial cells (RAEC); and second, to determine whether homocysteine activates NMDAr in the endothelium.
Methods: NR1 and NR2A, two NMDAr subunits, were probed in rat carotid arteries by immunohistochemistry. RNA was isolated from RAECs, and expression of all NMDAr subunits (NR1, 2A, 2B, 2C, and 2D) were examined by RT-PCR and sequencing. For receptor protein expression, RAEC were incubated with different homocysteine concentrations and incubation times and also were treated with 50 microM homocysteine and/or preincubated with 50 microM dizocilpine MK-801, an NMDAr inhibitor.
Results: Both NR1 and NR2A were expressed in rat carotid arteries. All NMDAr subunits were expressed in the RAECs, and there was 92% to 100% similarity compared with rat NMDAr from the National Center for Biotechnology Information (NCBI) GenBank. Homocysteine upregulated NR1 expression and increased cell proliferation. RAEC pretreatment with MK-801 reduced homocysteine-mediated cell proliferation.
Conclusion: This study is the first to show that NMDAr exists in the peripheral vasculature, and that homocysteine may act via NMDAr to increase intimal hyperplasia.
Clinical Relevance: Our objectives included the identification of a homocysteine receptor in the peripheral vasculature. The possible inhibition of a homocysteine receptor to prevent intimal hyperplasia rather than treat established stenosis would make a significant clinical impact. This will open further avenues of study in determining the role of homocysteine in the pathogenesis of intimal hyperplasia.
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http://dx.doi.org/10.1016/j.jvs.2005.02.021 | DOI Listing |
Biol Direct
December 2024
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Peroxisome proliferator-activated receptor-γ (PPARγ) is a critical regulator of adipogenesis and bone metabolism, playing complex roles in osteoporosis. This study investigates the effects of taurine and homocysteine on PPARγ, focusing on their roles in osteoclastogenesis and bone health. In-silico analyses, including molecular docking and molecular dynamic simulations, revealed that both taurine and homocysteine bind competitively to the PPARγ ligand-binding domain, exhibiting distinctive antagonistic modes, including destabilization of PPARγ's key helices H3, H4/5, H11, and H12.
View Article and Find Full Text PDFEpigenomics
January 2025
Mother and Child Health, ICMR - Collaborating Centre of Excellence (CCoE), Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.
Aim: This study aims to examine the gene expression and DNA methylation patterns of angiogenic factors in the placentae of Indian women who underwent assisted reproductive technology (ART) procedures and their association with maternal one-carbon metabolites and birth outcome.
Methods: Placental gene expression and DNA methylation of angiogenic factors (, , , ) in Indian women who underwent ART procedures ( = 64) and women who conceived naturally (Non-ART) ( = 93) was investigated using RT-qPCR and Epitect Methyl-II PCR assay kits. Maternal plasma one-carbon metabolites were assessed by CMIA technology.
Epigenetics
December 2024
Department of Medical Laboratory Technique, Kunming Medical University Haiyuan College, Kunming, Yunnan, P.R. China.
Atherosclerosis is a chronic inflammatory disease characterized by fatty plaque deposits on artery walls. Elevated plasma homocysteine (Hcy) levels are an independent risk factor for atherosclerosis. Research on the mechanism by which Hcy promotes atherosclerosis has gradually turned to epigenetic inheritance, but the correlation between Hcy and m6A (N6-methyladenosine) modification has not been reported.
View Article and Find Full Text PDFMol Psychiatry
November 2024
Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Medical Sciences, Toyoake, Aichi, Japan.
Negative experiences during adolescence, such as social isolation (SI), bullying, and abuse, increase the risk of psychiatric diseases in adulthood. However, the pathogenesis of psychiatric diseases induced by these factors remain poorly understood. In adolescents, stress affects the intestinal homeostasis in the gut-brain axis.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2024
Department Clinical Sciences, Faculty of Veterinary Sciences, Utrecht University, 3584 CM Utrecht, The Netherlands.
The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein.
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