PMID- 27903222
OWN - NLM
STAT- MEDLINE
DCOM- 20180712
LR  - 20180905
IS  - 1875-5631 (Electronic)
IS  - 1566-5232 (Linking)
VI  - 16
IP  - 5
DP  - 2017
TI  - Sustained ELABELA Gene Therapy in High-salt Diet-induced Hypertensive Rats.
PG  - 349-360
LID - 10.2174/1566523217666161121111906 [doi]
AB  - BACKGROUND: Elabela (ELA) is a recently identified apelin receptor agonist 
      essential for cardiac development, but its biology and therapeutic potential are 
      unclear. In humans, ELA transcripts are detected in embryonic stem cells, induced 
      pluripotent stem cells, kidney, heart and blood vessels. ELA through the apelin 
      (APJ) receptor promotes angiogenesis in vitro, relaxes murine aortic blood 
      vessels and attenuates high blood pressure in vivo. The APJ receptor when bound 
      to its original ligand, apelin, exerts peripheral vasodilatory and positive 
      inotropic effects, conferring cardioprotection in vivo. METHODS: This study 
      initially assessed endogenous ELA expression in normal and diseased rats and then 
      characterized the effects of long-term ELA gene delivery by adeno-associated 
      virus serotype 9 (AAV9) vectors on cardiorenal function in Dahl salt-sensitive 
      rats (DS) on a high-salt diet over 3 months. RESULTS: Endogenous ELA was 
      predominantly expressed in the kidneys, especially in the renal collecting duct 
      cells and was not affected by disease. Rat ELA was overexpressed in the heart via 
      AAV9 vector by a single intravenous injection. ELA-treated animals showed delayed 
      onset of blood pressure elevation. Prior to high-salt diet, a reduction in the 
      fractional sodium and chloride excretion was observed in rats given the AAV9-ELA 
      vector. After three months on a high-salt diet, ELA preserved glomerular 
      architecture, decreased renal fibrosis and suppressed expression of 
      fibrosis-associated genes in the kidneys. CONCLUSION: ELA is constitutively 
      expressed in renal collecting ducts in rats. Sustained AAV-ELA expression may 
      offer a potential long-term therapy for hypertension and renal remodeling.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Schreiber, Claire A
AU  - Schreiber CA
FAU - Holditch, Sara J
AU  - Holditch SJ
FAU - Generous, Alex
AU  - Generous A
FAU - Ikeda, Yasuhiro
AU  - Ikeda Y
AD  - Molecular Medicine, Mayo Clinic, 200 First St. SW, Rochester MN 55905, United 
      States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Gene Ther
JT  - Current gene therapy
JID - 101125446
RN  - 0 (Apelin Receptors)
RN  - 0 (Carrier Proteins)
RN  - 0 (Sodium Chloride, Dietary)
SB  - IM
MH  - Animals
MH  - Apelin Receptors/*agonists
MH  - Blood Pressure/genetics
MH  - Carrier Proteins/*genetics/metabolism
MH  - Dependovirus/genetics
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - Hypertension/etiology/genetics/*therapy
MH  - Kidney Tubules, Collecting/metabolism
MH  - Male
MH  - Rats, Inbred Dahl
MH  - Rats, Wistar
MH  - Sodium Chloride, Dietary/*adverse effects
OTO - NOTNLM
OT  - AAV
OT  - APJ
OT  - DS
OT  - Elabela
OT  - hypertension
OT  - renal fibrosis
EDAT- 2016/12/03 06:00
MHDA- 2018/07/13 06:00
CRDT- 2016/12/02 06:00
PHST- 2016/05/20 00:00 [received]
PHST- 2016/11/02 00:00 [revised]
PHST- 2016/11/18 00:00 [accepted]
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2018/07/13 06:00 [medline]
PHST- 2016/12/02 06:00 [entrez]
AID - CGT-EPUB-79834 [pii]
AID - 10.2174/1566523217666161121111906 [doi]
PST - ppublish
SO  - Curr Gene Ther. 2017;16(5):349-360. doi: 10.2174/1566523217666161121111906.