PMID- 36203611
OWN - NLM
STAT- MEDLINE
DCOM- 20221010
LR  - 20221012
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - IL-10 partly mediates the ability of MSC-derived extracellular vesicles to 
      attenuate myocardial damage in experimental metabolic renovascular hypertension.
PG  - 940093
LID - 10.3389/fimmu.2022.940093 [doi]
LID - 940093
AB  - Extracellular vesicles (EVs) obtain properties of immunomodulation and tissue 
      repair from their parental mesenchymal stem cells (MSCs), and upon delivery may 
      be associated with fewer adverse events. EVs derived from adipose-tissue MSCs 
      restored kidney function by attenuating kidney inflammation in a swine model of 
      metabolic syndrome (MetS) and renal artery stenosis via anti-inflammatory 
      pathways. EVs also ameliorated myocardial injury in renovascular hypertension 
      (RVH) secondary to inflammation in cardiorenal disease, but the mechanisms 
      regulating this effect are unknown. We hypothesize that the anti-inflammatory 
      cytokine interleukin (IL)-10 mediates the reparative effects of EVs on 
      cardiovascular complications in a preclinical swine model with coexisting MetS 
      and RVH. Twenty-three pigs established as Lean controls or RVH models were 
      observed for 16 weeks. At 12 weeks RVH subgroups received an intrarenal delivery 
      of 10(11) either wildtype (WT) EVs or EVs after IL-10 knockdown (KD) (RVH+WT-EVs 
      or RVH+IL-10-KD-EVs, respectively). Cardiac and renal function were studied 
      in-vivo and myocardial tissue injury in-vitro 4 weeks later. RVH pigs showed 
      myocardial inflammation, fibrosis, and left ventricular diastolic dysfunction. 
      WT-EVs attenuated these impairments, increased capillary density, and decreased 
      myocardial inflammation in-vivo. In-vitro, co-incubation with IL-10-containing 
      WT-EVs decreased activated T-cells proliferation and endothelial cells 
      inflammation and promoted their migration. Contrarily, these cardioprotective 
      effects were largely blunted using IL-10-KD-EVs. Thus, the anti-inflammatory and 
      pro-angiogenic effects of EVs in RVH may be partly attributed to their cargo of 
      anti-inflammatory IL-10. Early intervention of IL-10-containing EVs may be 
      helpful to prevent cardiovascular complications of MetS concurrent with RVH.
CI  - Copyright (c) 2022 Jiang, Hong, Zhu, Zhang, Tang, Jordan, Saadiq, Huang, Lerman, 
      Eirin and Lerman.
FAU - Jiang, Yamei
AU  - Jiang Y
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Hong, Siting
AU  - Hong S
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Zhu, Xiangyang
AU  - Zhu X
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Tang, Hui
AU  - Tang H
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Jordan, Kyra L
AU  - Jordan KL
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Saadiq, Ishran M
AU  - Saadiq IM
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Huang, Weijun
AU  - Huang W
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Lerman, Amir
AU  - Lerman A
AD  - Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States.
FAU - Eirin, Alfonso
AU  - Eirin A
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
FAU - Lerman, Lilach O
AU  - Lerman LO
AD  - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United 
      States.
LA  - eng
GR  - R01 HL158691/HL/NHLBI NIH HHS/United States
GR  - R21 AG062104/AG/NIA NIH HHS/United States
GR  - R01 DK122734/DK/NIDDK NIH HHS/United States
GR  - R01 DK120292/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220920
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/metabolism
MH  - Cytokines/metabolism
MH  - Endothelial Cells/metabolism
MH  - *Extracellular Vesicles/metabolism
MH  - *Heart Diseases/metabolism
MH  - *Hypertension, Renovascular/complications/metabolism/therapy
MH  - Inflammation/metabolism
MH  - Interleukin-10/metabolism
MH  - *Metabolic Syndrome/metabolism/therapy
MH  - Swine
PMC - PMC9530748
OTO - NOTNLM
OT  - extracellular vesicles
OT  - interleukin-10
OT  - mesenchymal stem cell
OT  - metabolic syndrome
OT  - myocardial damage
OT  - renovascular hypertension
COIS- LL is an advisor to AstraZeneca, CureSpec, Butterfly Biosciences, Beren 
      Therapeutics and Ribocure Pharmaceuticals. The remaining authors declare that the 
      research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2022/10/08 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/01/01
CRDT- 2022/10/07 02:37
PHST- 2022/05/09 00:00 [received]
PHST- 2022/08/31 00:00 [accepted]
PHST- 2022/10/07 02:37 [entrez]
PHST- 2022/10/08 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.940093 [doi]
PST - epublish
SO  - Front Immunol. 2022 Sep 20;13:940093. doi: 10.3389/fimmu.2022.940093. eCollection 
      2022.