The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(22), P. 4825 - 4829
Published: Oct. 27, 2023
This special issue of The Journal Physiology entitled ‘Extracellular vesicles in organ and systems function health disease’ originated from a focused symposium held at Experimental Biology April 2021 sponsored by Physiological Society the American Society. original on extracellular (EVs) as targets for cardiovascular (CV) health, examining role EVs couriers cellular information well their therapeutic potential. Contributors provided range perspectives benefits limitations using biomedical applications. has widened scope to move beyond CV focus cover translational potential across multiple body systems. Articles include two Symposium Reviews, eight Topical six research papers along with Club article Perspective article. combination these contributions leading experts field EV provides valuable insight into our current understanding EVs, importantly, appraises future clinical application. opening review this succinct evaluation knowledge that play physiological pathophysiological processes systems, organs cell types (Alqurashi et al., 2023). There is useful summary classification according biological origin, most commonly known being exosomes (derived endosomal pathway), ectosomes via budding plasma membrane) apoptotic cells). Current recommendations also suggest classifying size if origin unclear. What clear overview sheer diversity subtypes existence, likelihood more subpopulations emerging future. growing carriers material, drugs, evident, critically challenges underlying application Importantly, authors highlight need improved fate vivo, protocols production monitoring Given technical surrounding use applications highlighted Alqurashi al. (2023), it timely one Reviews focuses adapting bioengineering approaches enhance features specifically (Malekian highlights some properties that, upon modification, could enable drug delivery. These modification donor cells transfection express specific surface proteins, exosome–liposome hybridisation alter lipid profile exosomes, ligand improve targeted detailed numerous recent used exosome raises possibility techniques advanced targeting. As such, resource investigators field. Four articles system. Two reviews are symposium. not only disease, but biomarkers pathologies tools provide complexity EV-mediated communication system impact cargo can have function. consideration strengths strategies therapeutics outlined reader an awareness key focus. between different essential maintain healthy lead pathological consequences. Martins-Marques Girao (2023) how released populations influence neighbouring cardiomyocytes, cardiac fibroblasts, endothelial macrophages among considered, fascinating reflect cardioprotection. consider evidence mediating remodelling including myocardial infarction, hypertrophy fibrosis, atrial fibrillation. Aligned pathology, predictors risk. builds previous Osteikoetxea (2016) who importance source quantity system, suggesting numbers may ultimately be cardioprotective or pathogenic. In complementary Review, Neves emphasise correlation circulating risk severity disease. micro (mi)RNAs cardioprotection pathology disease biomarkers. attractive (low immunogenicity toxicity strong ability cross membranes) lend themselves raise delivery since loading desired (drugs, miRs, proteins) interfere structure therefore target host. They area development order design effective exosome-based methods Delving further mediate function, there Review included non-coding (nc)RNAs (Collado ncRNAs long (lnc)RNAs, miRNAs circular (circ)RNAs. contains very diagrams outlining many varied effects EV-derived both atherosclerosis progression coronary artery ischaemic heart fibrosis. accompanying text wide references covering complex cell–cell communication. previously reiterates characterise size, morphology concentration. present advantages disadvantages classical isolation, differential centrifugation, density gradient ultracentrifugation, size-exclusion chromatography, precipitation immunocapture. new approaches, atomic force microscopy, Raman spectroscopy, latter enabling characterisation content all one. theme characterise, image monitor comprises second (Ranjan associated designing therapeutics, short half-life adverse off-target effects. Efficient targeting challenge context Connexin 43, widely expressed gap junction protein (prevalent cardiomyocytes), exosomal contents and, when protein, protection against cardiotoxic drugs. reinforces connexin 43 (2023). Ranjan report studies cardiosphere-derived stem cell-derived shown repair, they stress delivering number required purposes demanding still uncertainty around actual content/cargo. track vivo another researchers covers currently used, such covalent binding tagged molecules surface, genetic modulation, metabolic labelling real-time imaging radiolabelling. methodology does tracking sub-populations carrying secreted same EV-based rely advances where lie. treatment acute stroke covered (Fullerton derived mesenchymal restoring neurological following stroke. similar vein relating details individual (including miRNA-124, miRNA-126, miRNA-98, miRNA-146 miRNA-181a) recovery. It significant alterations occur miRNA people experienced stroke, discuss those diagnostic prognostic emphasised methodological analytical isolation characterisation, example differences timing sampling, storage procedures accounting physiology. That said, even taking account, do appear common signatures changes indicates neuroregenerative therapy over cells. Since delivered systemically (they blood–brain barrier), favourable preclinical models look promising. liver (Srinivas show promise conditions viral hepatitis, fatty cancer. mainly stems large prospective trials pilot studies. hepatic laboratory modulation reduce certain pathologies. For example, GW4869, which pharmacological inhibitor release, increase transmission uninfected SHP099 (a SHP2 inhibitor) release pro-fibrogenic thus potentially reducing though lie fact inhibitors selective diseased vehicles treating seen nucleic acid-loaded siRNA gene silencing artificial exosome-mimetic nanovesicles, overcome low yields often isolated under conditions. paper, Chen investigate macrophage microvesicles (MMVs) intercellular lung MMVs carry transfer variety acids, proteins lipids study examines circRNAs chronic injury, injury induced methamphetamine (MA) abuse. paper first examine lncRNAs circ_YTHDF2 MMV-mediated alveolar uses primary material mouse model MA, bronchoalveolar lavage fluid MMVs) Results predominant form extracted culture. Following long-term MA (6 weeks mice up 24 h culture), increased apparent interestingly, uptake A heatmap circRNA microarray identifies significantly altered treatment. Knockdown control results levels tumour necrosis factor α, interleukin 6 adhesion molecule 1, indicating regulates immunoreactivity MMVs. By exploring cells, demonstrate si-circ_YTHDF2 exacerbate MA-induced inflammatory transition aortic Overexpression reverses injury. effectively demonstrates within supports Collado emphasising processes. terms other involved process. exponentially. One remains limited, yet hold tremendous potential, pregnancy. Farrelly literature investigating placental maternal pregnancy complications, pre-eclampsia, preterm birth, fetal growth restriction complications arising gestational diabetes. serves important gaps exist. During pregnancy, placenta enables bidirectional trafficking, enter vice versa. predict and/or diagnose Reported diabetes pre-eclampsia predictive diagnosis. possible alleviate dysfunction observed pre-eclampsia. normal induction labour term mechanisms birth. cause perinatal morbidity mortality, urgent intervention. administration pro-inflammatory pregnant day 15 resulted premature Studies humans found number, distribution during trimesters vary pregnancies go preterm. real lack treatment, basic clinicians obstetrics. roles exercise age physiology health. ageing five papers. explore pathophysiology, aged young individuals, separation identification individuals undergoing training. reports recovering muscle after disuse. Taken together, physiologists older McIlvenna Whitman small (sEVs), microparticles, process, this. Cellular senescence, occurring part ageing, involves factors senescence-associated secretory phenotype (SASP). contribution sEVs make SASP process clear, particularly suggests sEV reflected host senescent contributing human pluripotent (iPSCs) reverse anti-oxidant capacity iPSCs property, properly define ensure standardised. recurring message throughout 2023; Fullerton Srinivas promote remain elusive. cargos TMSB4X (important generation), glutathione peroxidase superoxide dismutase (both antioxidants) upregulated exercise. value proteomic datasets gather data deposited, will grow, guiding area. Five implications Together, give what vast intriguing high intensity intermittent training (HIIT) platelet-poor platelet-free plasma. Echoing views issue, standardised technique interpretation. particular, contaminating remnant platelets have. incorporated assessment single particle analysis, circumvents sample purification, platelet poor free HIIT alters expression tetraspanin proteins. Interestingly, depletion influences tetraspanins before analysis isolation. Another resting differ histories affect interpretation data. Darragh three groups (all male) were recreationally active, endurance trained strength trained. various identification, nanoparticle flow cytometry immunoblotting markers metabolomics performed each participant. blood samples comparable. work should males females thorough nonetheless, physiologists, inform confirming rest. Several type 2 ageing. reviewed recently Vechetti (2021) highlighting skeletal must communicate distal tissues through endocrine functions. prospect communicators route. Heiston aerobic decrease concentration fasting insulin-stimulated medium obese individuals. Previous suggested obesity indicate parallel lowered decreases AIx75 marker arterial stiffness) increases insulin sensitivity. EV–insulin interaction. paves way exercise-induced states. Indeed, (such miR-15a, miR22, miR-92a, miR122 miR-192) been positively correlate (Brandao 2023) would impacted addition beneficial conditions, mounting positive Xhuti examined resistance (12 weeks) (exosome-like (ELVs) ectosomes) ELV cargo. shows Circulating CD81+ CD9+ ELVs reduced (myomiRs) lower (miR-23a miR-27a). true circulation biopsies taken vitro myotube model. normalise back consistent young, subjects. article, Hamrick stresses findings reported notes rigor enabled detail subpopulation miR-23a 27a downregulation reversed result since, notes, Dicer (which plays biogenesis) group so global effect. effect miRs serve frailty intervention Wang analysed commended. echoes points made emphasises exclusion subsequent ultracentrifugation α-sarcoglycan identify muscle. have, elderly unable regularly effectively. Both note approach aid recovery disuse, explored Wu resident perivascular stromal (pericytes) produce antioxidant anti-inflammatory factors, acting natural defence damage. Using unilateral hindlimb immobilisation, RNA sequencing combined functional confirm response pericytes immobilised impaired. strategy priming H2O2, injection primed collagen myofibre immobilisation. unprimed pericytes. While proteome, determine exact responsible lies considerably research. reference sub-disciplines shed light perspective avenues lie, available EVs. Going forward, collection constructive basis direction Lastly, we pleased acknowledge published prior vesicles, microparticles 2015 Cardiff, UK 2015. (Krohn 2016; Morrison Ruiz 2016) additional related topics. Please note: publisher functionality any supporting supplied authors. Any queries (other than missing content) directed corresponding author No competing interests declared. S.C. H.S.: conception drafting revising intellectual content. read approved final version manuscript agree accountable aspects ensuring questions accuracy integrity appropriately investigated resolved. All persons designated qualify authorship, authorship listed. funding was received work.
Language: Английский