Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Backgruound: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation.
Methods: VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice.
Results: DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice.
Conclusion: Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633220 | PMC |
| http://dx.doi.org/10.3803/EnM.2022.1462 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure.
JACC Basic Transl Sci
September 2025
BHF Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, the Netherlands. Electronic address: andy.bak
Coronary artery bypass graft (CABG) surgery remains the gold standard of care to prevent myocardial ischemia in patients with advanced atherosclerosis; however, poor long-term graft patency remains a considerable and long-standing problem. Excessive vascular smooth muscle cell (SMC) proliferation in the grafted tissue is recognized as central to late CABG failure. We previously identified SMILR, a human-specific SMC-enriched long noncoding RNA that drives SMC proliferation, suggesting that targeting SMILR expression could be a novel way to prevent neointima formation, and thus CABG failure.
View Article and Find Full Text PDFFPR2 Agonism Attenuates Restenosis by Mitigating Neointimal Hyperplasia via ELOVL6.
FASEB J
September 2025
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Restenosis following endovascular intervention in lower extremity arterial disease contributes to significant morbidity and mortality. This study investigates the role of formylpeptide receptor 2 (FPR2) in neointimal hyperplasia and evaluates the therapeutic potential of the selective FPR2 agonist BMS-986235 in mitigating restenosis. FPR2 expression was significantly reduced in the popliteal and anterior tibial arteries of male amputees with restenosis compared to healthy controls.
View Article and Find Full Text PDFSCAP Interacts with Trim27 to Promote Vascular Neointimal Hyperplasia by Regulating the Stability and Ubiquitination of IκBα.
Aging Dis
August 2025
Centre for Lipid Research & Chongqing Key Laboratory of Metabolism on Lipid and Glucose, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University
Pathological vascular remodeling and intimal hyperplasia after vascular injury are representative pathological processes in age-associated vascular diseases. Previous data from our laboratory have indicated that sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) contributes to physiological angiogenesis during embryonic development. However, the role of SCAP in neointima formation is not fully understood.
View Article and Find Full Text PDFBACE2-Induced Aberrant Lymphatic Network Aggravates the Local Inflammation in Arteriovenous Fistulas With Hyperphosphatemia.
Adv Sci (Weinh)
August 2025
Department of Cardiovascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
As a widely used vascular access for hemodialysis patients, arteriovenous fistula (AVF) still faces high failure rates, in which local inflammatory response is an essential factor. In animal studies, chronic kidney disease (CKD) has been reported to aggravate local inflammation in AVFs, but the mechanisms are controversial. Here, spatial transcriptomics and single-cell RNA sequencing are used to explore the cellular changes during AVF remodeling in human and mouse.
View Article and Find Full Text PDFMicrovascular Endothelial Cells License APS Vasculopathy Through YAP1- and CCN2-Mediated Signaling.
Circulation
August 2025
Department of Internal Medicine, University of Michigan, Ann Arbor, MI. (H.S., W.L., C.K.H., Y. Shen, C.S., S.Y., P.K., L.H., C.E.V., A.T., J.A.M., Y.Z., P.-S.T., J.S.K.).
Background: Whereas antiphospholipid syndrome (APS) is best known for increasing the risk of macrovascular thrombosis, APS vasculopathy is characterized by the abnormal proliferation of endothelial and smooth muscle cells, leading to occlusion of small blood vessels in the skin, kidneys, and heart, among other organs. The underlying mechanisms remain unclear, and targeted treatment options for patients with APS are lacking.
Methods: To identify and analyze APS microvascular endothelial cells (MVECs), skin biopsies of patients with APS complicated by livedo racemosa were characterized using single-cell RNA sequencing.