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16 December 2022: Review Articles

A Review of the Roles of Apelin and ELABELA Peptide Ligands in Cardiovascular Disease, Including Heart Failure and Hypertension

Jan Rozwadowski ABCDEF , Sonia Borodzicz-Jażdżyk ACDEF , Katarzyna Czarzasta CDE , Agnieszka Cudnoch-Jędrzejewska ACDE*

DOI: 10.12659/MSM.938112

Med Sci Monit 2022; 28:e938112

Table 1 The role of apelinergic system in physiological conditions and cardiovascular diseases.

System/state concernedLigandMechanism of action and examined cellsResult of actionReference
Apelin-13Binding to the isolated single APJ cardiomyocytes from C57BL/6 mice↑ contractility↓ hypertrophy↓ calcium transientParikh et al []21
Apelin-13, apelin-13, and apelin-16Phosphorylation of the sarcolemmal NHEPositive inotropic effectSzokodi et al []22
ELASprague-Dawley rats↑ contractility augmentation of the left ventricle developed pressurecoronary vasodilationWang et al []Perjés et al []23
Apelin-13, apelin-13, and apelin-36Isolated human mammary artery cellsConcentration-dependent vasodilationMaguire et al []8
apelin-13Intracerebral infusion into Sprague-Dawley rats↑ arterial blood pressure↑ heart rateCzarzasta et al []Cudnoch-Jędrzejewska et al []28
Apelin-13Mouse kidney cortical collecting duct mpkCCD14 cellsWater excretion without electrolyte lossBoulkeroua et al []33
Apelin’s active fragments, K17F and pE13FSupraoptic nucleus’ vasopressinergic neurons of normotensive Wistar-Kyoto rats↓ antidiuretic hormone↓ dehydration-caused water intakeReaux et al []29
Apelin-17Female lactating Sprague-Dawley rats↑ diuresis (vasorelaxation of glomerular afferent arterioles)Hus-Citharel et al []34
Apelin-13Inhibition of the MAPK/ERK pathway in 3T3-L1 mice cells↓ lipolysis↑ expression of perilipin↓ free fatty acids releaseThan et al []35
Apelin-13C57BL/6J mice primary hepatocytes and isolated human HepG2 cells↑ glycogen formation in hepatocytesChu et al []36
ApelinNuclear translocation of the NF-κB in the isolated human umbilical vein↑ of molecules leading to vascular inflammatory states predisposing to atherosclerosisZhou et al []40
Apelin-12Wistar rats subjected to a myocardial infarction caused by left anterior descending artery ligation↓ lactate accumulation↓ tissue damage↓ creatine kinasePisarenko et al [] Halestrap et al [] Brancaccio et al []42
ELAPlasma concentration of ELA in patients on their first day of ST-Elevation myocardial infarctionSignificantly higher plasma concentrations in both inferior and anterior myocardial infarction; assessed to negatively correlate with left ventricle ejection fractionDönmez et al []48
Apelin-13C57BL/6J mice↓ Ang II-induced hypertension↓ cardiovascular fibrosisSiddiquee et al []50
ApelinApelin-Apolipoprotein E double-knockout mice whose mutation results in reduced cardiac contractility and increased total plasma cholesterol levelsSignificant increase in net NO bioavailabilityChun et al []39
Apelin-17Wistar rats↓ arterial blood pressure NO-dependent mechanismTatemoto et al []51
Apelin-12 structural analogueIsolated Wistar rat hearts previously subjected to global ischemia and subsequently reperfused↑ endothelial NO synthase and NO production – vasodilation and reduction of the infarct areaPisarenko et al []54
Apelin-13Isolated human preadipocytes↓ production of antioxidants↓ reactive oxygen speciesThan et al []57
Apelin-13C57BL/6J mice↑ progenitor cells↑ angiogenesis↑ density of the myocardial capillaries↑ arteriole formation↓ myocardial apoptosisLi et al []58
Apelin-13Sprague-Dawley rats subjected to left coronary artery occlusion with subsequent reperfusion↓ apoptosis via PI3K and MEK1/2protection against ischemia/reperfusion injuryTao et al []60
apelin-13Isolated Sprague Dawley rat hearts after 35 minutes of ischemia and 120 minutes of reperfusion↓ infarct sizeKleinz et al []61
Apelin-13Naïve mouse cardiac fibroblasts with apelin↓ collagen production↓ endothelial proliferationPchejetski et al []62
Apelin-12Isolated cardiac fibroblasts of C57BL/6J mice↓ fibrotic responses in cardiac fibroblasts↓ transformation into myofibroblastsFalcão-Pires et al []7
Apelin-13Male C57BL/6J mice↓ left ventricular end diastolic area↑ heart rate↑ ventricular elastance↑ preload↑ velocity of circumferential shortening↑ cardiac outputAshley et al []63
Apelin-16Activation of the of the sarcolemmal NHE in cultured neonatal rat cardiac myocytes↑ conduction velocity – antiarrhythmic actionFarkasfalvi et al []67
Apelin-12Patients with atrial fibrillationLower plasma concentration in patients suffering from atrial fibrillation than in the control groupGurger et al []68
NHE – sarcolemmal Na+–H+ exchanger; MAPK/ERK – mitogen-activated protein kinases/extracellular signal-regulated kinases; NF-κB – nuclear Factor Kappa-light-chain-enhancer of activated B cells; Ang II – angiotensin II; NO – nitric oxide; PI3K – phosphoinositide 3-kinase; MEK 1/2 – mitogen-activated protein kinases/extracellular signal-regulated kinase 1/2.

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750