Macrophage-Derived Exosomal Mir-155 Regulating Cardiomyocyte Pyroptosis and Hypertrophy in Uremic Cardiomyopathy

Wang, Bin; Wang, Ze‐Mu; Ji, Jialing; Gan, Weihua; Zhang, Aiqing; Shi, Haojie; Wang, Hao; Lv, Lin‐Li; Li, Zuo‐Lin; Tang, Tao-Tao; Du, Jie; Wang, Xiaonan H.; Liu, Bi-Cheng

doi:10.1016/j.jacbts.2019.10.011

Cited by 67 publications

(49 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, BMDMs lacking miR-155 were more susceptible to apoptosis during infection, suggesting that miR-155 has an antiapoptotic function (62). Notably, miR-155 regulates multiple cell death pathways, as macrophage derived miR-155 containing exosomes enhanced pyroptosis in cardiomyocytes through the direct targeting of FoxO3a (63). Human monocyte derived foam cells, obtained after prolonged exposure to oxidized LDL [a known inducer of miR-155 expression (46,64)], respond to inflammasome activation preferentially with pyroptosis combined with other types of necrotic death (65).…”

Section: Discussionmentioning

confidence: 99%

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

et al. 2020

View full text Add to dashboard Cite

BackgroundAtherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD).MethodsmiR-155 expression was quantified in aortae from ApoE−/− mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD.ResultsHere, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs.ConclusionmiR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Also, miR-155 in macrophage EVs has shown to favor a profibrotic cardiac environment in several studies. For example, following MI in mice, miR-155 was upregulated in cardiac macrophages from which it was released in EVs that mediated its transfer into cardiac fibroblasts where it inhibited proliferation and promoted inflammation by suppressing expression of, respectively, Son of Sevenless 1 and SOCS1 [ 181 ] while, in a model of uremic cardiomyopathy in mice, miR-155 in macrophage EVs targeted Foxo3a in cardiomyocytes, resulting in pyroptosis (pro-inflammatory programmed cell death) and downstream cardiac hypertrophy and fibrosis [ 182 ].…”

Section: Cardiac Fibrosismentioning

confidence: 99%

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Brigstock

2021

Cells

View full text Add to dashboard Cite

Fibrosis is the unrelenting deposition of excessively large amounts of insoluble interstitial collagen due to profound matrigenic activities of wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It is a highly debilitating pathology that affects millions of people globally and leads to decreased function of vital organs and increased risk of cancer and end-stage organ disease. Extracellular vesicles (EVs) produced within the chronic wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many of the cell types involved in driving the fibrotic response. On the other hand, EVs from sources such as stem cells, uninjured parenchymal cells, and circulation have in vitro and in vivo anti-fibrotic activities that have provided novel and much-needed therapeutic options. Finally, EVs in body fluids of fibrotic individuals contain cargo components that may have utility as fibrosis biomarkers, which could circumvent current obstacles to fibrosis measurement in the clinic, allowing fibrosis stage, progression, or regression to be determined in a manner that is accurate, safe, minimally-invasive, and conducive to repetitive testing. This review highlights the rapid and recent progress in our understanding of EV-mediated fibrotic pathogenesis, anti-fibrotic therapy, and fibrosis staging in the lung, kidney, heart, liver, pancreas, and skin.

show abstract

“…Although the rat is an extremely useful model for studying cardiomyopathy of renal failure ( 6 , 7 ), there are currently many genetic manipulations in mice, and it is easier to perform additional genetic manipulations in the mouse system. The 5/6 nephrectomy (5/6Nx) ( 8 – 10 ), uninephrectomy plus contralateral ischemia followed by reperfusion (IR) ( 11 ), pole ligation ( 12 ) and adenine diet models ( 13 ) of uraemic cardiomyopathy in mice have been reported in recent years. However, mice are small, and surgery is more difficult than surgery in rats.…”

Section: Introductionmentioning

confidence: 99%

Uraemic Cardiomyopathy in Different Mouse Models

Chen

Xie

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Uraemic cardiomyopathy (UCM) is one of the most common complications in chronic kidney disease (CKD). Our aim was to compare characteristics of various UCM mouse models. Mice were assigned to the following groups: the pole ligation group, 5/6 nephrectomy group (5/6Nx), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR), adenine group, and sham group. Mice were sacrificed at 4, 8, and 16 weeks after surgery in the pole ligation, 5/6Nx, and IR groups, respectively. In the adenine group, mice were sacrificed at 16 weeks after the adenine diet. The structure and function of the heart and the expression of fibroblast growth factor 23 (FGF-23) and growth differentiation factor 15 (GDF-15) in hearts were assessed. The mortality in the 5/6 Nx group was significantly higher than that in the pole ligation, IR, and adenine groups. Echocardiogram and histological examination showed cardiac hypertrophy in the adenine,5/6Nx, ligation group, and IR group. In addition, cardiac fibrosis occurred in all CKD modeling groups. Interestingly, cardiac fibrosis was more serious in the IR and adenine groups. FGF-23 expression in sham mice was similar to that in modeling groups; however, the GDF-15 level was decreased in modeling groups. Our results suggest that the four models of UCM show different phenotypical features, molding time and mortality. GDF-15 expression in the hearts of UCM mice was downregulated compared with sham group mice.

show abstract

Macrophage-Derived Exosomal Mir-155 Regulating Cardiomyocyte Pyroptosis and Hypertrophy in Uremic Cardiomyopathy

Cited by 67 publications

References 58 publications

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Uraemic Cardiomyopathy in Different Mouse Models

Contact Info

Product

Resources

About