Key result
AAV9-mediated Elabela gene therapy delays hypertension and reduces renal fibrosis in salt-sensitive rats.
Why the study?
The biology and therapeutic potential of Elabela (ELA), an apelin receptor agonist essential for cardiac development, remain unclear.
Does Elabela gene therapy delay blood pressure elevation and prevent renal remodeling in Dahl salt-sensitive rats on a high-salt diet?
Does Elabela gene therapy delay blood pressure elevation and prevent renal remodeling in Dahl salt-sensitive rats on a high-salt diet?
Sustained Elabela gene therapy via AAV9 vector delays blood pressure elevation and protects against renal remodeling in a rat model of salt-induced hypertension.
Should not yet inform clinical practice; hypothesis-generating for Elabela gene therapy in salt-sensitive hypertension.
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.
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Schreiber et al. (2017) studied Hypertension and renal remodeling. Elabela (ELA) gene delivery by AAV9 vectors was evaluated on Blood pressure elevation and renal fibrosis. AAV9-mediated Elabela gene therapy delayed blood pressure elevation, preserved glomerular architecture, and decreased renal fibrosis in salt-sensitive rats on a high-salt diet.
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