First trimester circulating miR-208b-3p and miR-26a-1-3p are relevant to the prediction of gestational hypertension DOI Creative Commons
Andrée‐Anne Clément, Cécilia Légaré,

Véronique Desgagné

et al.

BMC Pregnancy and Childbirth, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 8, 2025

Abstract Background Gestational hypertension (GH) is linked to an increased risk of cardiometabolic diseases for both mother and child, but we lack reliable biomarkers identify high-risk women early in pregnancy. MicroRNAs (miRNAs) are small non-coding RNA that have emerged as promising pregnancy complications. We thus aimed first trimester circulating miRNAs associated with GH build a miRNA-based algorithm predict incidence. Methods quantified using next-generation sequencing plasma samples collected at Gen3G ( N = 413, including 28 cases) 3D 281, 21 prospective birth cohorts. MiRNAs (identified DESeq2, p -value < 0.05) replicated were included stepwise logistic regression model estimate the probability developing based on (normalized z-score counts) maternal characteristics contribute most model. Results identified onset later cohort. Among these, three cohort (similar fold change 0.1) models GH-related factors. When combined mean arterial pressure (MAP), miR-208b-3p miR-26a-1-3p achieve AUC 0.803 (95%CI: 0.512–0.895) 0.709 0.588–0.829) 3D. The addition miR-208b-3p, significantly improves prediction performance over MAP alone 0.03). then proposed low thresholds, which could help very those who benefit from prevention monitoring throughout their Conclusion combination offers good predictors GH. Interestingly, these target pathways related cardiovascular system be relevant pathophysiology These provide novel avenue lead even more adequate obstetrical care reduce complications

Language: Английский

Cuproptosis: p53-regulated metabolic cell death? DOI Creative Commons
Xiong Chen, Hong Ling, Qian Hao

et al.

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(4), P. 876 - 884

Published: Feb. 8, 2023

Abstract Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with lipoylated proteins tricarboxylic acid cycle, leading disulfide-bond-dependent aggregation these proteins, destabilization iron-sulfur cluster and consequent proteotoxic stress. Cancer prefer glycolysis (Warburg effect) for producing intermediate metabolites energy, thereby achieving resistance cuproptosis. Interestingly, tumor suppressor p53 crucial regulator inhibits drives switch towards cancer cells. Additionally, regulates biogenesis clusters copper chelator glutathione, which are two critical components cuproptotic pathway, suggesting this might play role Furthermore, possible roles mutant regulating cuproptosis discussed. In essay, we review recent progress understanding mechanism underlying cuproptosis, revisit regulation glutathione biosynthesis, propose several potential mechanisms wild-type p53-mediated regulation.

Language: Английский

Citations

147
Understanding the complexity of p53 in a new era of tumor suppression DOI
Yanqing Liu, Zhenyi Su, Omid Tavana

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(6), P. 946 - 967

Published: May 9, 2024

Language: Английский

Citations

116
The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension DOI Creative Commons

Yeshun Wu,

Hongqing Xu,

Xiaoming Tu

et al.

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 28, 2021

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases, its development involves multiple mechanisms. Gut microbiota has been reported to be closely linked hypertension. Short-chain fatty acids (SCFAs)—the metabolites of gut microbiota—participate in hypertension through various pathways, including specific receptors, immune system, autonomic nervous metabolic regulation gene transcription. This article reviews the possible mechanisms SCFAs regulating blood pressure prospects as target prevent treat

Language: Английский

Citations

72
It’s Getting Complicated—A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy DOI Creative Commons
Che-Pei Kung, Jason D. Weber

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Jan. 26, 2022

Anti-tumorigenic mechanisms mediated by the tumor suppressor p53, upon oncogenic stresses, are our bodies’ greatest weapons to battle against cancer onset and development. Consequently, factors that possess significant p53-regulating activities have been subjects of serious interest from research community. Among them, MDM2 ARF considered most influential p53 regulators due their abilities inhibit activate functions, respectively. inhibits promoting ubiquitination proteasome-mediated degradation while activates physically interacting with block its access p53. This conventional understanding p53-MDM2-ARF functional triangle guided direction research, as well development p53-based therapeutic strategies for last 30 years. Our increasing knowledge this during time, especially through identification p53-independent functions ARF, uncovered many under-appreciated molecular connecting these three proteins. Through recognizing both antagonizing synergizing relationships among consideration harnessing develop effective therapies needs an update accordingly. In review, we will re-visit wisdom regarding tumor-regulating mechanisms, highlight impactful studies contributing modern look relationships, summarize ongoing efforts target pathway treatments. A refreshed appreciation network can bring innovative approaches new generations genetically-informed clinically-effective therapies.

Language: Английский

Citations

49
The role of p53 in the alternation of vascular functions DOI Creative Commons
Gabriel Hoi Huen Chan, Enoch Chan, Carsten Tsun‐Ka Kwok

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 6, 2022

Ageing is a risk factor for many degenerative diseases. Cardiovascular diseases (CVDs) are usually big burdens elderly, caregivers and the health system. During aging process, normal functions of vascular cells tissue progressively lost eventually develop Endothelial dysfunction, reduced bioavailability endothelium-derived nitric oxide usual phenomena observed in patients with cardiovascular Myriad studies have been done to investigate delay dysfunction or improve function prolong process. Tumor suppressor gene p53, also transcription factor, act as gatekeeper regulate number genes maintain cell including but not limited proliferation, apoptosis. p53 crosstalk other key factors like hypoxia-inducible 1 alpha that contribute progression Therefore, recent three decades, has drawn scientists’ attention on its effects function. Though role tumor still clear function, it found play regulatory roles may involve remodeling, atherosclerosis pulmonary hypertension. divergent endothelial muscle those conditions. In this review, we describe different physiology. Further cell-specific deficiency atherosclerotic plaque formation common animal models required before therapeutic potential can be realized.

Language: Английский

Citations

40
The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets DOI Creative Commons

Bing Jiang,

Xuan Zhou, Tao Yang

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 29, 2023

Autophagy is a conserved lysosomal pathway for the degradation of cytoplasmic proteins and organelles, which realizes metabolic needs cells renewal organelles. Autophagy-related genes (ATGs) are main molecular mechanisms controlling autophagy, their functions can coordinate whole autophagic process. also play role in cardiovascular disease through several key signaling pathways, including PI3K/Akt/mTOR, IGF/EGF, AMPK/mTOR, MAPKs, p53, Nrf2/p62, Wnt/β-catenin NF-κB pathways. In this paper, we reviewed cross-interference between autophagy diseases, analyzed development status novel treatment by targeting core mechanism as well critical pathway. Induction or inhibition pathways provide therapeutic benefits patients. Meanwhile, hope to unique insight into strategies understanding crosstalk diseases.

Language: Английский

Citations

36
SIRT3 Deficiency Enhances Ferroptosis and Promotes Cardiac Fibrosis via p53 Acetylation DOI Creative Commons
Han Su, Aubrey C. Cantrell, Jian‐Xiong Chen

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1428 - 1428

Published: May 19, 2023

Cardiac fibrosis plays an essential role in the development of diastolic dysfunction and contributes to heart failure with preserved ejection fraction (HFpEF). Our previous studies suggested Sirtuin 3 (SIRT3) as a potential target for cardiac failure. In present study, we explored SIRT3 ferroptosis its contribution fibrosis. data showed that knockout resulted significant increase ferroptosis, increased levels 4-hydroxynonenal (4-HNE) downregulation glutathione peroxidase 4 (GPX-4) mouse hearts. Overexpression significantly blunted response erastin, known inducer, H9c2 myofibroblasts. Knockout p53 acetylation. Inhibition acetylation by C646 alleviated To further explore involvement SIRT3-mediated crossed acetylated mutant (p534KR) mice, which cannot activate SIRT3KO mice. SIRT3KO/p534KR mice exhibited reduction less compared Furthermore, cardiomyocyte-specific (SIRT3-cKO) Treatment SIRT3-cKO inhibitor ferrostatin-1 (Fer-1) led We concluded was partly through mechanism involving acetylation-induced

Language: Английский

Citations

34
Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism DOI Creative Commons

Dandan Xiao,

Wenguang Chang, Xiang Ao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: 15(3), P. 1589 - 1607

Published: Jan. 2, 2025

Iron overload is strongly associated with heart disease. Ferroptosis a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism myocardial injury caused by iron still unclear, and involvement ferroptosis overload-induced not fully understood. In this study, we observed that participated developing I/R-induced cardiomyopathy. Mechanistically, discovered Parkin inhibited cardiomyocytes promoting ubiquitination long-chain acyl-CoA synthetase 4 (ACSL4), crucial protein involved ferroptosis-related lipid metabolism pathways. Additionally, identified p53 as transcription factor transcriptionally suppressed expression iron-overloaded cardiomyocytes, thereby regulating ferroptosis. animal studies, cardiac-specific knockout mice (Myh6-CreER T2 /Parkin fl/fl ) fed high-iron diet presented more severe damage, high levels exacerbated I/R inhibitor Fer-1 significantly Moreover, effectively protected against impaired mitochondrial function prevented peroxidation. These findings unveil novel regulatory pathway involving p53-Parkin-ACSL4 disease inhibiting

Language: Английский

Citations

1
Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies DOI Creative Commons
Joseph Adu‐Amankwaah,

Qiang You,

Xinying Liu

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Pulmonary hypertension (PH) stands as a tumor paradigm cardiovascular disease marked by hyperproliferation of cells and vascular remodeling, culminating in heart failure. Complex genetic epigenetic mechanisms collectively contribute to the disruption pulmonary homeostasis. In recent years, advancements research technology have identified numerous gene deletions mutations, addition bone morphogenetic protein receptor type 2, that are closely associated with remodeling process PH. Additionally, modifications such RNA methylation, DNA histone modification, noncoding RNAs been shown precisely regulate PH molecular networks cell-type-specific manner, emerging potential biomarkers therapeutic targets. This review summarizes analyzes roles currently genes factors PH, emphasizing pivotal role long ncRNAs its regulation. it examines current clinical preclinical therapies for targeting these explores new treatment strategies.

Language: Английский

Citations

1
Targeting DNA damage response in cardiovascular diseases: from pathophysiology to therapeutic implications DOI
Lin Wu, James R. Sowers, Yingmei Zhang

et al.

Cardiovascular Research, Journal Year: 2022, Volume and Issue: 119(3), P. 691 - 709

Published: May 9, 2022

Cardiovascular diseases (CVDs) arise from a complex interplay among genomic, proteomic, and metabolomic abnormalities. Emerging evidence has recently consolidated the presence of robust DNA damage in variety cardiovascular disorders. triggers series cellular responses termed response (DDR) including detection lesions, cell cycle arrest, repair, senescence, apoptosis, all organ systems hearts vasculature. Although transient DDR to temporary can be beneficial for function, persistent activation promotes onset development CVDs. Moreover, therapeutic interventions that target have potential attenuate dysfunction improve disease outcome. In this review, we will discuss molecular mechanisms repair CVDs, explore how specific cardiac types contributes highlight latest advances regarding strategies targeting signalling

Language: Английский

Citations

34