Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway DOI Creative Commons
Bing Yan, Yu Zhang, Chun Liang

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(15), P. 6728 - 6742

Published: Jan. 1, 2020

Rational: Ischemic injury of the skeletal muscle remains a serious clinical problem and currently there is no effective therapy. The aim present study to determine whether human umbilical cord mesenchymal stem cells- derived exosomes (UMSC-Exo) could repair ischemic by releasing circular RNA. Methods Results: To create hindlimb ischemia, we surgically ligated left femoral artery in C57BL/6 mice. Using circRNA-seq analyses total RNA from control muscles, found reduced expression circHIPK3 muscle. explore role injury, mice were randomly assigned into three groups after surgery: 1) vehicle; 2) UMSC-Exo; 3) UMSC-Exo siRNA targeting (UMSC-Exo /si-circHIPK3). treatment significantly increased improved blood perfusion, running distance force, which reversed injection /si-circHIPK3, suggesting that improve function circHIPK3. also inhibited ischemia induced pyroptosis - cell death caused inflammasome as evidenced activation NLRP3, cleaved caspase-1, subsequent increase IL-1β IL-18, effects /si-circHIPK3. Bioinformatic analysis identified miR-421/FOXO3a potential target for circHIPK3, was confirmed luciferase reporter assay. Knockdown C2C12 cells resulted miR-421. We established an vitro model stimulating with LPS ATP. ATP miR-421, prevented UMSC-Exo. Western blot showed levels NLRP3 caspase-1 when treated FOXO3a presence miR-421 inhibitor, Importantly, upregulated but si-circHIPK3 present. Conclusions: loss/gain-of method, demonstrated direct prevent turn down regulate resulting FOXO3a, leading inhibition release IL-18.

Language: Английский

The role of cellular senescence in cardiac disease: basic biology and clinical relevance DOI

Mozhdeh Mehdizadeh,

Martín Aguilar, Éric Thorin

et al.

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 19(4), P. 250 - 264

Published: Oct. 19, 2021

Language: Английский

Citations

186
Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload DOI Creative Commons
Junyan Wang, Bo Deng, Qing Liu

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(7)

Published: July 24, 2020

Abstract Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and a severe health issue faced by elderly population. Mixed lineage kinase 3 (MLK3), member MAP3K family, associated with aging, inflammation, oxidative stress, related such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function myocardial fibrosis unknown. To investigate fibrosis, we inhibited expression MLK3, examined cardiac remodeling TAC mice. In addition, assessed protein ventricular cells downstream protein. We found that mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation pyroptosis causes early stages Similarly, JNK/p53 stress ferroptosis advanced promoting miR-351 can inhibit significantly improve mice subjected TAC. These results suggest induced cardiomyocytes are essential for adverse response pressure overload. Furthermore, miR-351, which protective effect on caused overload, may be key target regulation MLK3.

Language: Английский

Citations

174
Interleukin-1 blockade in cardiovascular diseases: a clinical update DOI Open Access
Leo F. Buckley, Antonio Abbate

European Heart Journal, Journal Year: 2018, Volume and Issue: 39(22), P. 2063 - 2069

Published: Feb. 23, 2018

Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical clinical research has defined important roles for atherosclerosis, acute myocardial infarction (AMI), heart failure (HF). promotes formation of atherosclerotic plaque facilitates its progression complication. In large phase III trial stable patients with prior AMI, blocking activity using monoclonal antibody prevented recurrent atherothrombotic cardiovascular events. also contributes to adverse remodelling left ventricular dysfunction after II studies, blockade quenched inflammatory response associated ST-segment elevation AMI HF. established HF, thought impair beta-adrenergic receptor signalling intracellular calcium handling. Phase studies HF show improved exercise capacity blockade. Thus, poised enter arena an additional strategy reduce residual risk and/or address conditions refractory standard treatments. There are several blockers available use, which differ mechanism action, potentially efficacy safety. While not immunosuppressive opportunistic infections or increased cancer, fatal may occur more frequently while on treatment likely due blunting signs infection leading delayed presentation diagnosis. We discuss practical use blockade, including considerations patient selection safety monitoring.

Language: Английский

Citations

168
COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches DOI Creative Commons
Francesco Moccia, Andrea Gerbino, Vincenzo Lionetti

et al.

GeroScience, Journal Year: 2020, Volume and Issue: 42(4), P. 1021 - 1049

Published: May 20, 2020

Language: Английский

Citations

159
Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway DOI Creative Commons
Bing Yan, Yu Zhang, Chun Liang

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(15), P. 6728 - 6742

Published: Jan. 1, 2020

Rational: Ischemic injury of the skeletal muscle remains a serious clinical problem and currently there is no effective therapy. The aim present study to determine whether human umbilical cord mesenchymal stem cells- derived exosomes (UMSC-Exo) could repair ischemic by releasing circular RNA. Methods Results: To create hindlimb ischemia, we surgically ligated left femoral artery in C57BL/6 mice. Using circRNA-seq analyses total RNA from control muscles, found reduced expression circHIPK3 muscle. explore role injury, mice were randomly assigned into three groups after surgery: 1) vehicle; 2) UMSC-Exo; 3) UMSC-Exo siRNA targeting (UMSC-Exo /si-circHIPK3). treatment significantly increased improved blood perfusion, running distance force, which reversed injection /si-circHIPK3, suggesting that improve function circHIPK3. also inhibited ischemia induced pyroptosis - cell death caused inflammasome as evidenced activation NLRP3, cleaved caspase-1, subsequent increase IL-1β IL-18, effects /si-circHIPK3. Bioinformatic analysis identified miR-421/FOXO3a potential target for circHIPK3, was confirmed luciferase reporter assay. Knockdown C2C12 cells resulted miR-421. We established an vitro model stimulating with LPS ATP. ATP miR-421, prevented UMSC-Exo. Western blot showed levels NLRP3 caspase-1 when treated FOXO3a presence miR-421 inhibitor, Importantly, upregulated but si-circHIPK3 present. Conclusions: loss/gain-of method, demonstrated direct prevent turn down regulate resulting FOXO3a, leading inhibition release IL-18.

Language: Английский

Citations

153