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GADD34 activates p53 and may have utility as a marker of atherosclerosis
Front Med (Lausanne). 2023 May 9;10:1128921. doi: 10.3389/fmed.2023.1128921. eCollection 2023.ABSTRACTWe previously identified growth arrest and DNA-damage-inducible gene 34 (GADD34) as a marker of ischemic stroke. In the present study, serum levels of anti-GADD34 antibodies were found to be significantly higher in patients with acute ischemic stroke or chronic kidney disease compared to healthy donors. We then examined the biological function of GADD34 by transfection into U2OS human osteosarcoma and U87 human glioblastoma cells. Knockdown of GADD34 by siRNA resulted in enhanced cell proliferation, which was reversed by c...
Source: Atherosclerosis - May 25, 2023 Category: Cardiology Authors: Go Tomiyoshi Rika Nakamura Natsuko Shinmen Yoichi Yoshida Seiichiro Mine Toshio Machida Katsuro Iwase Yasuo Iwadate Takaki Hiwasa Hideyuki Kuroda Source Type: research

Fine-tuning of microglia polarization prevents diabetes-associated cerebral atherosclerosis
In this study, we showed that polarization of microglia, the resident macrophage in the central nervous system, appeared to play a critical role in the pathological progression of cerebral atherosclerosis. Microglia likely underwent an M2c-like polarization in an environment long exposed to high glucose. Experimental suppression of microglia M2c polarization was achieved through transduction of microglia with an adeno-associated virus (serotype AAV-PHP.B) carrying siRNA for interleukin-10 (IL-10) under the control of a microglia-specific TMEM119 promoter, which significantly attenuated diabetes-associated cerebral atherosc...
Source: Atherosclerosis - August 8, 2022 Category: Cardiology Authors: Xuan Zhu Pengfei Xing Ping Zhang Minmin Zhang Hongjian Shen Lei Chen Fang Shen Yi Jiang Hui Yuan Lei Zhang Jing Wang Xiongfeng Wu Yu Zhou Tao Wu Benqiang Deng Jianmin Liu Yongwei Zhang Pengfei Yang Source Type: research

The enigmatic role of VCAM-1 expressed by macrophages in mitochondrial metabolism and atherosclerosis
CONCLUSION: We conclude that macrophage-specific VCAM-1 augments mitochondrial biogenesis and DNA oxidation via Cmpk2. Oxidized mitochondrial DNA in plaque macrophages increases inflammation via Sting, resulting in exacerbation of atherosclerosis.PMID:35557156 | DOI:10.1096/fasebj.2022.36.S1.R6141
Source: Atherosclerosis - May 13, 2022 Category: Cardiology Authors: Niranjana Natarajan Jonathan Florentin Scott P O'Neil Lee L Ohayon Partha Dutta Source Type: research

A Transcriptional Regulation Bioinformatics Pipeline to Predict Co-Regulated Genes in Vascular Smooth Muscle Cell Phenotypic Transitions During Atherosclerosis
This study proposes a novel systems biology pipeline that integrates experimental and computational tools with large datasets measuring the transcriptomes and epigenomes of phenotypically transitioning VSMCs. Our pipeline allows users to identify candidate transcription factors that co-regulate mouse or human gene sets controlling specific VSMC phenotypic transitions during atherosclerosis. The computational algorithms developed in this workflow integrate an array of publicly available databases, such as the Ensembl genome database and the JASPAR transcription factor database. To demonstrate the translational potential of ...
Source: Atherosclerosis - May 13, 2022 Category: Cardiology Authors: Mahima S Reddy Vlad Serbulea Sohel Shamsuzzaman Anita Salamon Rupa Tripathi Clint Miller Giuseppe Mocci Johan Bj örkegren Gary Owens Source Type: research

DL-3-n-butylphthalide prevents oxidative stress and atherosclerosis by targeting Keap-1 and inhibiting Keap-1/Nrf-2 interaction
Eur J Pharm Sci. 2022 Mar 5:106164. doi: 10.1016/j.ejps.2022.106164. Online ahead of print.ABSTRACTAtherosclerosis is the common pathophysiological foundation of ischaemic stroke and myocardial ischaemia. Oxidative stress is intricately related to the progress of atherosclerosis. DL-3-n-butylphthalide (NBP) is a synthesized raceme of L-3-n-butylphthalide that is first isolated from celery. As a neuroprotective agent, NBP also exhibits potent antioxidative activity. Our research aimed to evaluate the effect of NBP on atherosclerosis and to explore the underlying antioxidative mechanisms and targets. Firstly, we detected the...
Source: Atherosclerosis - March 8, 2022 Category: Cardiology Authors: Jibo Han Xiaowen Shi Jiajun Xu Wante Lin Yanghao Chen Bingjiang Han Yi Wang Jianjiang Xu Source Type: research

Low-density Lipoprotein-Cholesterol Lowering Strategies for Prevention of Atherosclerotic Cardiovascular Disease: Focus on siRNA Treatment Targeting PCSK9 (Inclisiran)
AbstractPurpose of ReviewThe aim of low-density lipoprotein-cholesterol (LDL-C) lowering therapies is to safely achieve a consistent and long-term reduction in exposure of the vasculature to atherogenic lipoproteins in order to reduce the risk of atherosclerotic cardiovascular (CV) disease and the associated CV events, such as myocardial infarctions and ischemic strokes. This review summarizes the concept and clinical development of a novel molecular approach to efficiently lower LDL-C, a synthetic small interfering ribonucleic acid (siRNA) —inclisiran—directed against proprotein convertase subtilisin-kexin type 9 (PCS...
Source: Current Cardiology Reports - October 21, 2020 Category: Cardiology Source Type: research

Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction.
CONCLUSION: Adrenal βarrestin1 upregulation is one of the mechanisms by which tobacco compounds, like nicotine, promote cardio-toxic hyperaldosteronism in vitro and in vivo. Thus, adrenal βarrestin1 represents a novel therapeutic target for tobacco-related heart disease prevention or mitigation. PMID: 32547713 [PubMed]
Source: World Journal of Cardiology - May 25, 2020 Category: Cardiology Authors: Cora N, Ghandour J, Pollard CM, Desimine VL, Ferraino KE, Pereyra JM, Valiente R, Lymperopoulos A Tags: World J Cardiol Source Type: research

Future role of proprotein convertase subtilisin/kexin type 9 inhibitors in preventive cardiology
Purpose of review The use of therapeutic monoclonal antibodies to target proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a novel approach to the management of hypercholesteremia and prevention of atherosclerotic cardiovascular disease. We review the most recent literature relevant to PCSK9 inhibition with emphasis on how recent results and ongoing trials have and will continue to shape the use of this new therapeutic class in preventive cardiology. Recent findings PCSK9 inhibitors reduce plasma lipoprotein(a) concentrations but a mechanistic understanding remains elusive. Evaluation of evolocumab for ...
Source: Current Opinion in Cardiology - August 8, 2019 Category: Cardiology Tags: PREVENTION: Edited by Ron Blankstein Source Type: research

Xanthoangelol Prevents Ox-LDL–Induced Endothelial Cell Injury by Activating Nrf2/ARE Signaling
Conclusions: These data suggest that XAG cytoprotects against Ox-LDL–induced cell injury through activating Nrf2/ARE–mediated antioxidative stress. Cumulatively, these findings show that EX has the potential to prevent and treat AS.
Source: Journal of Cardiovascular Pharmacology - August 1, 2019 Category: Cardiology Tags: Original Article Source Type: research