Table 2.

Regulatory roles of the elabela/apelin-APJ axis in hypertension and related diseases.

Experimental model/population	Experimental intervention	Effects	References
Patients with essential hypertension	–	↓Circulating elabela levels	[12]
Ang II-induced hypertensive mice	Elabela	↓Blood pressure levels	[16]
		Improvement of cardiac dysfunction
High-salt diet-induced hypertensive rats	Elabela	↓Blood pressure levels	[17]
Anesthetized normotensive animals	Apelin	↓Blood pressure levels	[19]
Diabetic mice	Apelin	↓Intrarenal arteries constriction	24,25
Hypertensive rats	Elabela-32	↓Blood pressure levels	[28]
		↓RAS activity
Hypertensive rats	–	↓APJ mRNA and protein	32,33
Conscious sheep	Apelin	↑Blood pressure levels	[38]
		↑Peripheral vascular resistance
Conscious rats	Apelin	↑Blood pressure levels	[49]
Hypertensive rats with ADMA-damaged endothelial barrier	Apelin 13	↑Vasoconstriction	39,40
ICR mice	Apelin	↑Blood pressure levels	[41]
Normotensive rats	Apelin	↑Blood pressure levels	45,46
Rats’ aortic adventitial fibroblasts	Elabela	↓Apoptosis	[51]
		↓Autophagy
		↓Vascular remodeling
Rats with pulmonary hypertension	Elabela	↓Right ventricular systolic pressure levels	[52]
		↓Ventricular hypertrophy
		↓Pulmonary vascular remodeling
Elabela KO mice	Elabela	↓Blood pressure levels	[54]
		↓Proteinuria
Patients with essential hypertension	–	↓Circulating apelin levels	[55]
		Cardiac dysfunction
Patients with aortic valve stenosis	–	↓Apelin	[56]
		↑Pro-BNP
Patients with end-stage heart failure	Apelin-13	Improvement of cardiac dysfunction	[57]
VSMCs	Apelin-13	↑VSMC cell cycle	60,61
		↑VSMC proliferation
		↑PI3K/AKT/ERK
		↑Jagged-1/Notch3
PASMCs	Apelin	↓Cellular proliferation	[62]
		↓Cellular migration
		↑PI3K/AKT/mTOR
ApoE KO mice	Apelin	↑NO formation	[65]
		↓Ang II-induced atherosclerosis

ADMA: Asymmetric dimethylarginine; AKT: Protein kinase B; Ang II: Angiotensin II; APJ: Apelin receptor; ERK: Extracellular signal-regulated kinase; ICR: Institute of Cancer Research; KO: Knock out; mTOR: Mammalian target of rapamycin; NO: Nitric oxide; PASMCs: Pulmonary arterial smooth muscle cells; PI3K: Phosphatidylinositol 3-kinase; Pro-BNP: Pro-brain natriuretic peptide; RAS: Renin-angiotensin system; VSMCs: Vascular smooth muscle cells.