MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration DOI Open Access
Jason Colasanti, Joseph B. Lin, Ryo Terao

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 15, 2025

Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute loss, but high treatment burden and efficacy with chronic therapy highlight need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as key regulator aging age-related diseases, its role neovascular AMD unclear. In an injury-induced murine CNV model, we discovered miR-34a promoted pathological angiogenesis, without altering expression Vegfa or receptor Kdr, canonical regulators CNV. Mechanistically, directly targets inhibits transcription KLF2 thereby upregulating pro-angiogenic factors CXCR4 CXCL12. Finally, show exacerbates aged mice expressed lesions excised from wet patients. These findings establish causal link between AMD. Identification molecular mechanism involved pathogenesis prevalent debilitating ocular disease.

Язык: Английский

Associations between systemic immune-inflammation index and abdominal aortic calcification: Results of a nationwide survey DOI
Ruijie Xie, Xiaozhu Liu,

Haiyang Wu

и другие.

Nutrition Metabolism and Cardiovascular Diseases, Год журнала: 2023, Номер 33(7), С. 1437 - 1443

Опубликована: Апрель 23, 2023

Язык: Английский

Процитировано

56

The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities DOI Creative Commons
Yu Sun, Xia Wang, Tianwei Liu

и другие.

Cell & Bioscience, Год журнала: 2022, Номер 12(1)

Опубликована: Май 31, 2022

Abstract Background The global population of older individuals is growing, and ageing a key risk factor for atherosclerotic cardiovascular diseases. Abnormal accumulation senescent cells can cause potentially deleterious effects on the organism with age. As vital marker cellular senescence, senescence-associated secretory phenotype (SASP) novel mechanism to link senescence atherosclerosis. Main body In this review, we concretely describe characteristics SASP its regulation mechanisms. Importantly, provide perspectives how promote from different types have roles in atherosclerosis progression. significant mediator harmful cells, it play pro-atherogenic role by producing inflammation immune dysfunction. Furthermore, deliver signals surrounding vascular gradually contributing development Finally, focus variety therapeutic strategies aimed reduce burden elderly targeting inhibiting regulatory mechanisms SASP. Conclusion This review systematically summarizes multiple contribute exploration new opportunities.

Язык: Английский

Процитировано

61

Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases DOI Creative Commons

Cuncun Hua,

Xinming Liu, Lirong Liang

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 8

Опубликована: Янв. 27, 2022

Cardiovascular diseases (CVDs) are still the main cause of morbidity and mortality worldwide include a group disorders varying from vasculature, myocardium, arrhythmias cardiac development. MicroRNAs (miRs) endogenous non-coding RNAs with 18-23 nucleotides that regulate gene expression. The miR-34 family, including miR-34a/b/c, plays vital role in regulation myocardial physiology pathophysiological processes. Recently, miR-34a has been implicated cardiovascular fibrosis, dysfunction related as an essential regulator. Interestingly, there is pivotal link among miR-34a, Smad4/TGF-β1 signaling. Notably, both loss-of-function gain-of-function approaches identified critical roles apoptosis, autophagy, inflammation, senescence remodeling by modulating multifunctional signaling pathways. In this article, we focus on current understanding biogenesis, its biological effects implications for pathologies infarction, heart failure, ischaemia reperfusion injury, cardiomyopathy, atherosclerosis, hypertension atrial fibrillation. Thus, further will aid development effective interventions. Targeting emerged potential therapeutic target diseases.

Язык: Английский

Процитировано

58

More than Just a Monolayer: the Multifaceted Role of Endothelial Cells in the Pathophysiology of Atherosclerosis DOI Creative Commons
Marion Mußbacher, Klaudia Schossleitner, Julia B. Kral‐Pointner

и другие.

Current Atherosclerosis Reports, Год журнала: 2022, Номер 24(6), С. 483 - 492

Опубликована: Апрель 11, 2022

Abstract Purpose of the Review In this review, we summarize current insights into versatile roles endothelial cells in atherogenesis. Recent Findings The vascular endothelium represents first barrier that prevents entry lipoproteins and leukocytes vessel wall, thereby controlling two key events pathogenesis atherosclerosis. Disturbance homeostasis increases permeability, inflammation, cellular trans-differentiation, which not only promotes build-up atherosclerotic plaques but is also involved life-threatening thromboembolic complications such as plaque rupture erosion. focus on recent findings lipoprotein transport, transitions, function. Summary By using cutting-edge technologies single-cell sequencing, epigenetics, cell fate mapping, novel regulatory mechanisms phenotypes have been discovered, challenged established concepts activation, led to a different view disease.

Язык: Английский

Процитировано

55

A framework of biomarkers for vascular aging: a consensus statement by the Aging Biomarker Consortium DOI Creative Commons
Le Zhang, Jun Guo, Yuehong Liu

и другие.

Life Medicine, Год журнала: 2023, Номер 2(4)

Опубликована: Авг. 30, 2023

Aging of the vasculature, which is integral to functioning literally all human organs, serves as a fundamental physiological basis for age-related alterations well shared etiological mechanism various chronic diseases prevalent in elderly population. China, home world's largest aging population, faces an escalating challenge addressing prevention and management these conditions. To meet this challenge, Biomarker Consortium China has developed expert consensus on biomarkers vascular (VA) by synthesizing literature insights from scientists clinicians. This provides comprehensive assessment associated with VA presents systemic framework classify them into three dimensions: functional, structural, humoral. Within each dimension, panel recommends most clinically relevant biomarkers. For functional domain, reflecting stiffness endothelial function are highlighted. The structural dimension encompasses metrics structure, microvascular distribution. Additionally, proinflammatory factors emphasized humoral dimension. aim establish foundation assessing extent conducting research related VA, ultimate goal improving health globally.

Язык: Английский

Процитировано

27

Senescent cardiac fibroblasts: A key role in cardiac fibrosis DOI Creative Commons
José Miguel Osorio,

Claudio Espinoza-Pérez,

Constanza Rimassa-Taré

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(4), С. 166642 - 166642

Опубликована: Янв. 18, 2023

Язык: Английский

Процитировано

25

Therapeutic applications of miRNA in the management of obesity and osteoporosis DOI Creative Commons
Sakhavat Abolhasani, Yasin Ahmadi,

Yavar Rostami

и другие.

Journal of Diabetes & Metabolic Disorders, Год журнала: 2025, Номер 24(1)

Опубликована: Март 3, 2025

Obesity and osteoporosis are interrelated global health challenges, both characterized by dysregulated bone metabolism adipose tissue dynamics, contributing to increased fracture risk systemic complications. Emerging evidence underscores the pivotal role of microRNAs (miRNAs) as regulatory molecules governing intricate balance between adipogenesis osteogenesis, thereby providing a molecular link these two conditions. Both disorders alterations in which increase fractures Recent advancements biology have identified miRNAs crucial regulators disorders, influencing differentiation marrow mesenchymal stem cells (BMSCs) into osteoblasts (bone-forming cells) adipocytes (fat-storing cells). This review provides comprehensive analysis dual modulating osteogenesis adipogenesis, with particular focus on their implications disease progression therapeutic strategies. It first explores how specific regulate critical energy metabolism, inflammation, remodeling pathways. By integrating insights from biology, endocrinology, clinical practice, highlights potential miRNA-based interventions. Targeting could restore offering innovative approaches simultaneously address obesity osteoporosis. These proposed strategies hold promise for improving patient outcomes mitigating risk, enhancing density, addressing metabolic dysfunctions associated obesity. Ultimately, future research should translating applications develop effective therapies that tackle complex interplay prevalent

Язык: Английский

Процитировано

1

Metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway in osteoarthritis DOI Creative Commons

Shiju Yan,

Wenjing Dong,

Zhirui Li

и другие.

Journal of Orthopaedic Surgery and Research, Год журнала: 2023, Номер 18(1)

Опубликована: Март 13, 2023

Osteoarthritis (OA) is the most common degenerative disease in joints among elderly patients. Senescence deeply involved pathogenesis of osteoarthritis. Metformin widely used as first-line drug for Type 2 diabetes mellitus (T2DM), and has great potential treatment other aging-related disorders, including OA. However, role metformin OA not fully elucidated. Therefore, our aim here was to investigate effects on human chondrocytes.After treatment, expression level microRNA-34a SIRT1 chondrocyte were detected with quantitative real-time PCR immunofluorescence staining. Then, mimic small interfering RNA (siRNA) against (siRNA-SIRT1) transfected into chondrocyte. Senescence-associated β-galactosidase (SA-β-gal) staining performed assess senescence. Chondrocyte viability illustrated MTT colony formation assays. Western blot conducted detect P16, IL-6, matrix metalloproteinase-13 (MMP-13), Collagen type II (COL2A1) Aggrecan (ACAN).We found that (1 mM) inhibited while promoted chondrocytes. Both miR-34a mimics siRNA SA-β-gal assay confirmed reduced SA-β-gal-positive rate chondrocytes, transfection or siRNA-SIRT1 reversed it. showed accelerated proliferation, weakened this effect. Furthermore, results from western demonstrated suppressed senescence-associated protein proinflammatory cytokine IL-6 catabolic gene MMP-13 elevated anabolic proteins such Aggrecan, which could be attenuated by mimics.Overall, data suggest regulates senescence proliferation through microRNA-34a/SIRT1 pathway, indicating it a novel strategy treatment.

Язык: Английский

Процитировано

19

miR-34a/TAN1/CREB Axis Engages in Alleviating Oligodendrocyte Trophic Factor-Induced Myelin Repair Function and Astrocyte-Dependent Neuroinflammation in the Early Stages of Alzheimer's Disease: The Anti-Neurodegenerative Effect of Treadmill Exercise DOI
Yang Liu,

Xiao-Kang Meng,

Wen-zhen Shao

и другие.

Neurochemical Research, Год журнала: 2024, Номер 49(4), С. 1105 - 1120

Опубликована: Янв. 30, 2024

Язык: Английский

Процитировано

9

Small extracellular vesicle-mediated CRISPR-Cas9 RNP delivery for cardiac-specific genome editing DOI
Dasom Mun, Jiyoung Kang, Hyoeun Kim

и другие.

Journal of Controlled Release, Год журнала: 2024, Номер 370, С. 798 - 810

Опубликована: Май 18, 2024

Язык: Английский

Процитировано

8