Role of long noncoding RNAs in pathological cardiac remodeling after myocardial infarction: An emerging insight into molecular mechanisms and therapeutic potential

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116248 - 116248

Published: Feb. 6, 2024

Myocardial infarction (MI) is the leading cause of heart failure (HF), accounting for high mortality and morbidity worldwide. As a consequence ischemia/reperfusion injury during MI, multiple cellular processes such as oxidative stress-induced damage, cardiomyocyte death, inflammatory responses occur. In next stage, proliferation activation cardiac fibroblasts results in myocardial fibrosis HF progression. Therefore, developing novel therapeutic strategy urgently warranted to restrict progression pathological remodeling. Recently, targeting long non-coding RNAs (lncRNAs) provided insight into treating several disorders. this regard, numerous investigations have indicated that lncRNAs could participate pathogenesis MI-induced remodeling, suggesting their potential applications. review, we summarized displayed pathophysiology remodeling after emphasizing molecular mechanisms. Also, highlighted possible translational role targets condition discussed exosomes delivering involved post-MI

Language: Английский

---

BMSCs-derived small extracellular vesicles antagonize cerebral endothelial Caveolin-1 driven autophagic degradation of tight-junction proteins to protect blood-brain barrier post-stroke

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(2), P. 842 - 859

Published: Jan. 1, 2025

Bone marrow mesenchymal stem cells (BMSCs) -derived extracellular vesicles (EVs), especially small EVs (sEVs), were vastly reported to enable multiple restorative effects on ischemic stroke, yet the protective mechanism of blood-brain barrier (BBB) has not been fully illustrated.In present study, we investigated therapeutic and BMSCs-derived sEVs BBB injury after stroke.In-vivo, administering transient middle cerebral artery occlusion (tMCAo) mice mitigated brain infarct volume, permeability neural apoptosis, improved blood flow perfusion neurological function.Simultaneously, vascular endothelial overexpressed Caveolin-1 (Cav-1) together with its strong co-localization autophagosome protein LC3B suppressed, ZO-1 Occludin expressions enhanced, whose results consistent those oxygen-glucose-deprivation/reperfusion (OGD/R)-insulted (BECs) in vitro.Furthermore, by employing Cav-1 siRNA pcDNA3.1 transfection, Co-immunoprecipitation, cycloheximide assay, molecular docking, it proved that was an essential upstream autophagy activation, contributing tight-junction proteins delegation via autophagy-lysosomal pathway.Altogether, our study demonstrates novel Cav-1-dependent autophagic disruption integrity BMSC-sEVs treatment can reverse such hazard cascades.

Language: Английский

---

Exosomes as Biomarkers and Therapeutic Agents in Neurodegenerative Diseases: Current Insights and Future Directions

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Abstract Neurodegenerative diseases (NDs) like Alzheimer’s, Parkinson’s, and ALS rank among the most challenging global health issues, marked by substantial obstacles in early diagnosis effective treatment. Current diagnostic techniques frequently demonstrate inadequate sensitivity specificity, whilst conventional treatment strategies encounter challenges related to restricted bioavailability insufficient blood–brain barrier (BBB) permeability. Recently, exosomes—nanoscale vesicles packed with proteins, RNAs, lipids—have emerged as promising agents potential reshape therapeutic approaches these diseases. Unlike drug carriers, they naturally traverse BBB can deliver bioactive molecules affected neural cells. Their molecular cargo influence cell signaling, reduce neuroinflammation, potentially slow neurodegenerative progression. Moreover, exosomes serve non-invasive biomarkers, enabling precise while allowing real-time disease monitoring. Additionally, engineered exosomes, loaded molecules, enhance this capability targeting diseased neurons overcoming barriers. By offering enhanced reduced immunogenicity, an ability bypass physiological limitations, exosome-based present a transformative advantage over existing approaches. This review examines multifaceted role of NDDs, emphasizing their capabilities, intrinsic functions, advanced vehicles.

Language: Английский

---

Circular RNA regulatory role in pathological cardiac remodelling

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Cardiac remodelling involves structural, cellular and molecular alterations in the heart after injury, resulting progressive loss of function ultimately leading to failure. Circular RNAs (circRNAs) are a recently rediscovered class non-coding that play regulatory roles pathogenesis cardiovascular diseases, including Thus, more comprehensive understanding role circRNAs processes governing cardiac may set ground for development circRNA-based diagnostic therapeutic strategies. In this review, current knowledge about circRNA origin, conservation, characteristics is summarized. Bioinformatics wet-lab methods used research discussed. The mechanisms such as cell death, cardiomyocyte hypertrophy, inflammation, fibrosis metabolism highlighted. Finally, key challenges opportunities discussed, orientations future work address pharmacological potential failure proposed.

Language: Английский

---

Erythrocyte-Derived microRNAs: Emerging Players in Cardiovascular and Metabolic Disease

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2023, Volume and Issue: 43(5), P. 628 - 636

Published: March 16, 2023

Recent studies have demonstrated a novel function of red blood cells (RBCs) beyond their classical role as gas transporters, that is, RBCs undergo functional alterations in cardiovascular and metabolic disease, RBC dysfunction is associated with hypertension the development injury type 2 diabetes, heart failure, preeclampsia, familial hypercholesterolemia/dyslipidemia, COVID-19. The underlying mechanisms include decreased nitric oxide bioavailability, increased arginase activity, reactive oxygen species formation. Of interest, contain diverse abundant micro (mi)RNAs. miRNA expression pattern reflects whole blood, serum, plasma. levels been found to be altered various diseases, which contributes complications. Evidence has shown RBC-derived miRNAs interact system via extracellular vesicles argonaute RISC catalytic component carriers. Alteration RBC-to-vascular communication may serve potential disease mechanism for vascular present review summarizes released mediators injury. We further focus on possible by regulate function. A better understanding will increase insights into targets treatment

Language: Английский

---

Both extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles are involved in gastric/extragastric diseases

European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)

Published: Nov. 6, 2023

Abstract Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role infectious diseases cancers. Among these Helicobacter pylori ( H. ) is particularly important bacterium implicated various gastrointestinal disorders, gastric cancers, systemic illnesses. achieves effects by stimulating host cells to secrete EVs generating internal outer membrane (OMVs). The derived from -infected modulate inflammatory signaling pathways, thereby affecting cell proliferation, apoptosis, cytokine release, immune modification, endothelial dysfunction, well disrupting cellular junctional structures inducing cytoskeletal reorganization. In addition, OMVs isolated play pivotal shaping subsequent immunopathological responses. These incite both immunosuppressive reactions within environment, facilitating pathogen evasion of defenses invasion cells. Despite this growing understanding, research involving -derived remains its early stages across different domains. comprehensive review, we present recent advancements elucidating contributions EV components, such non-coding RNAs (ncRNAs) proteins, pathogenesis extragastric diseases. Furthermore, highlight their potential utility biomarkers, therapeutic targets, vehicles for targeted delivery.

Language: Английский

---

Advances in Purification, Modification, and Application of Extracellular Vesicles for Novel Clinical Treatments

Membranes, Journal Year: 2022, Volume and Issue: 12(12), P. 1244 - 1244

Published: Dec. 8, 2022

Extracellular vesicles (EV) are membrane surrounded by a lipid bilayer and include microvesicles, apoptotic bodies, exosomes, exomeres. Exosome-encapsulated microRNAs (miRNAs) released from cancer cells involved in the proliferation metastasis of tumor via angiogenesis. On other hand, mesenchymal stem cell (MSC) therapy, which is being employed regenerative medicine owing to ability MSCs differentiate into various cells, due humoral factors, including messenger RNA (mRNA), miRNAs, proteins, lipids, encapsulated exosomes derived transplanted cells. New treatments that advocate cell-free therapy using MSC-derived will significantly improve clinical practice. Therefore, highly purified perform their original functions desirable. In this review, we summarized advances purification, modification, application EVs as novel strategies treat some diseases.

Language: Английский

---

Immunometabolism, extracellular vesicles and cardiac injury

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Recent evidence from our lab and others suggests that metabolic reprogramming of immune cells drives changes in cell phenotypes along the inflammatory-to-reparative spectrum plays a critical role mediating inflammatory responses to cardiac injury (e.g. hypertension, myocardial infarction). However, factors drive are not fully understood. Extracellular vesicles (EVs) recognized for their ability transfer cargo such as microRNAs remote sites influence remodeling. Furthermore, conditions obesity syndrome, which implicated majority cardiovascular disease (CVD) cases, can skew production EVs toward pro-inflammatory phenotypes. In this mini-review, we discuss mechanisms by may metabolism during associated with syndrome disrupt normal EV function. We also potential sources cardio-protective anti-inflammatory EVs, brown adipose tissue. Finally, implications future therapeutics.

Language: Английский

---

miR‐210 as a therapeutic target in diabetes‐associated endothelial dysfunction

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract Background and Purpose MicroRNA (miR)‐210 function in endothelial cells its role diabetes‐associated dysfunction are not fully understood. We aimed to characterize the miR‐210 study therapeutic potential diabetes. Experimental Approach Two different diabetic mouse models ( db/db Western diet‐induced), knockout transgenic mice, isolated vessels human were used. Key Results levels lower aortas from than control mice. Endothelium‐dependent relaxation (EDR) was impaired this restored by inhibiting downstream protein tyrosine phosphatase 1B (PTP1B), mitochondrial glycerol‐3‐phosphate dehydrogenase 2 (GPD2), oxidative stress. Inhibition of these pathways also improved EDR both models. High glucose reduced aortas, effects that reversed overexpressing miR‐210. However, plasma affected individuals with type diabetes (T2D) following glycaemic status. Of note, genetic overexpression using mice pharmacological mimic vivo ameliorated decreasing PTP1B, GPD2 Genetic altered aortic transcriptome, genes involved decreased nitric oxide production high cells. Conclusion Implications This unravels mechanisms which down‐regulated induces T2D demonstrates serves as a novel target.

Language: Английский

---

Chymase Activity in Plasma and Urine Extracellular Vesicles in Primary Hypertension

Kidney360, Journal Year: 2024, Volume and Issue: 5(11), P. 1613 - 1622

Published: Aug. 22, 2024

Key Points Blood and urine extracellular vesicles isolated from hypertensive patients possess high chymase enzymatic activity. Chymase activity was significantly higher in small obtained with suboptimal BP control. Background Circulating (EVs) carry protected cargoes of nucleic acids, proteins, metabolites. In this study, we identified validated the surface proteins chymase, angiotensin converting enzymes 1 (ACE) 2 (ACE2), neprilysin (NEP) EVs blood primary patients. Methods Peripheral venous spot 34 were processed to isolate plasma urinary EVs. Immunogold labeling transmission electron microscopy presence exosomal marker protein CD63 on Flow cytometry characterized for CD63, CD9, CD81 markers. addition, TSG101, Alix analyzed by western blotting. Urinary did not express endoplasmic reticulum calnexin Golgi GM130. Chymase, ACE, ACE2, NEP activities 125 I substrates—angiotensin-(1–12) (Ang-[1–12]) II—(1 nmol/L each) quantified HPLC. Data based whether patient's controlled (group 1: <140/80 mm Hg) or noncontrolled 2: ≥140/80 Hg). Results Ang-(1–12) than NEP. more three-fold increased retrieved group No comparable differences found between 2. Conclusions These studies reveal a differential renin system Demonstrating comparatively expands previously documented finding

Language: Английский

---