PMID- 31260338
OWN - NLM
STAT- MEDLINE
DCOM- 20200908
LR  - 20200908
IS  - 1557-8682 (Electronic)
IS  - 1527-0297 (Linking)
VI  - 20
IP  - 3
DP  - 2019 Sep
TI  - Age-Dependent Systemic Effects of a Systemic Intermittent Hypoxic Therapy In 
      Vivo.
PG  - 221-230
LID - 10.1089/ham.2018.0113 [doi]
AB  - Introduction: The adaptive response to systemic intermittent hypoxic therapy 
      (SIHT) may be used for therapeutic advances due to the activation of multiple 
      pathways involved in angiogenesis, immunomodulation, and tissue homeostasis. The 
      aim of this study was to investigate the early age-dependent systemic response of 
      different exposures of SIHT in mice. Materials and Methods: Sixty-four C57BL/6NRj 
      female mice in three different age groups, young (4-5 weeks), adolescent (8-10 
      weeks), and adults (23-32 weeks), were exposed to SIHT. Different algorithms for 
      equal hypoxic challenges (oxygen-decrease*time) were investigated to allow 
      examination of the role of absolute hypoxia (oxygen-decrease) compared with 
      relative hypoxia (total oxygen depletion over time). The systemic effects of 
      angiogenetic regulation were investigated using blood samples analyzed by ELISA, 
      proteome profiles, and proximity extension immunoassay. One-way analysis of 
      variance with post hoc Bonferroni analyses was performed. Results: The early 
      systemic response to SIHT was dependent on the absolute hypoxia rather than 
      relative hypoxia over time. Serum erythropoietin (EPO) levels were increased 
      significantly in young mice receiving low-oxygen SIHT treatments (10% and 15% 
      oxygen). The expression of angiogenic proteins differed between the different age 
      groups indicating an age-dependent response to SIHT. Focusing on 
      hypoxia-inducible factor-1 (HIF-1) signaling, there was a trend toward 
      upregulated angiogenetic response with younger age. Furthermore, clustering of 
      protein expression in low-oxygen SIHT algorithms were found between young and 
      adolescent mice. In adult mice, the majority of the proteins were downregulated 
      as a response to SIHT. The systemic response of metabolites expressions was most 
      pronounced in young mice. Systemic levels of cardiac troponin I (Tnni3) was 
      unaffected by SIHT independent of age groups. Conclusions: The systemic response 
      to SIHT is dependent on the absolute hypoxic exposure rather than the relative 
      hypoxic depletion over time. Age-dependent effects of a short-term SIHT were 
      associated with an increase in EPO, upregulation of angiogenetic pathways, and 
      select metabolic and cell-surface proteins.
FAU - Bergholt, Natasja Leth
AU  - Bergholt NL
AD  - Orthopaedic Research Laboratory, Department of Clinical Medicine, Aarhus 
      University Hospital, Aarhus, Denmark.
AD  - Comparative Medicine Lab, Department of Clinical Medicine, Aarhus University 
      Hospital, Aarhus, Denmark.
FAU - Olesen, Morten Lykke
AU  - Olesen ML
AD  - Orthopaedic Research Laboratory, Department of Clinical Medicine, Aarhus 
      University Hospital, Aarhus, Denmark.
FAU - Foldager, Casper Bindzus
AU  - Foldager CB
AD  - Orthopaedic Research Laboratory, Department of Clinical Medicine, Aarhus 
      University Hospital, Aarhus, Denmark.
AD  - Comparative Medicine Lab, Department of Clinical Medicine, Aarhus University 
      Hospital, Aarhus, Denmark.
AD  - Department of Orthopaedics, Aarhus University Hospital, Aarhus, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190701
PL  - United States
TA  - High Alt Med Biol
JT  - High altitude medicine & biology
JID - 100901183
RN  - 0 (Cytokines)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (TNNI3 protein, human)
RN  - 0 (Troponin I)
RN  - 11096-26-7 (Erythropoietin)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Erythropoietin/blood
MH  - Female
MH  - Hypoxia/*physiopathology/*therapy
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Leukocyte Count
MH  - Mice, Inbred C57BL
MH  - Oxygen/*administration & dosage
MH  - Proteomics
MH  - Troponin I/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - angiogenesis
OT  - inflammation
OT  - intermittent systemic hypoxia
OT  - mice
OT  - proteomics
EDAT- 2019/07/02 06:00
MHDA- 2020/09/09 06:00
CRDT- 2019/07/02 06:00
PHST- 2019/07/02 06:00 [pubmed]
PHST- 2020/09/09 06:00 [medline]
PHST- 2019/07/02 06:00 [entrez]
AID - 10.1089/ham.2018.0113 [doi]
PST - ppublish
SO  - High Alt Med Biol. 2019 Sep;20(3):221-230. doi: 10.1089/ham.2018.0113. Epub 2019 
      Jul 1.