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 concerned | Ligand | Mechanism of action and examined cells | Result of action | Reference |
|---|---|---|---|---|
| Apelin-13 | Binding to the isolated single APJ cardiomyocytes from C57BL/6 mice | ↑ contractility↓ hypertrophy↓ calcium transient | Parikh et al []21 | |
| Apelin-13, apelin-13, and apelin-16 | Phosphorylation of the sarcolemmal NHE | Positive inotropic effect | Szokodi et al []22 | |
| ELA | Sprague-Dawley rats | ↑ contractility augmentation of the left ventricle developed pressurecoronary vasodilation | Wang et al []Perjés et al []23 | |
| Apelin-13, apelin-13, and apelin-36 | Isolated human mammary artery cells | Concentration-dependent vasodilation | Maguire et al []8 | |
| apelin-13 | Intracerebral infusion into Sprague-Dawley rats | ↑ arterial blood pressure↑ heart rate | Czarzasta et al []Cudnoch-Jędrzejewska et al []28 | |
| Apelin-13 | Mouse kidney cortical collecting duct mpkCCD14 cells | Water excretion without electrolyte loss | Boulkeroua et al []33 | |
| Apelin’s active fragments, K17F and pE13F | Supraoptic nucleus’ vasopressinergic neurons of normotensive Wistar-Kyoto rats | ↓ antidiuretic hormone↓ dehydration-caused water intake | Reaux et al []29 | |
| Apelin-17 | Female lactating Sprague-Dawley rats | ↑ diuresis (vasorelaxation of glomerular afferent arterioles) | Hus-Citharel et al []34 | |
| Apelin-13 | Inhibition of the MAPK/ERK pathway in 3T3-L1 mice cells | ↓ lipolysis↑ expression of perilipin↓ free fatty acids release | Than et al []35 | |
| Apelin-13 | C57BL/6J mice primary hepatocytes and isolated human HepG2 cells | ↑ glycogen formation in hepatocytes | Chu et al []36 | |
| Apelin | Nuclear translocation of the NF-κB in the isolated human umbilical vein | ↑ of molecules leading to vascular inflammatory states predisposing to atherosclerosis | Zhou et al []40 | |
| Apelin-12 | Wistar rats subjected to a myocardial infarction caused by left anterior descending artery ligation | ↓ lactate accumulation↓ tissue damage↓ creatine kinase | Pisarenko et al [] Halestrap et al [] Brancaccio et al []42 | |
| ELA | Plasma concentration of ELA in patients on their first day of ST-Elevation myocardial infarction | Significantly higher plasma concentrations in both inferior and anterior myocardial infarction; assessed to negatively correlate with left ventricle ejection fraction | Dönmez et al []48 | |
| Apelin-13 | C57BL/6J mice | ↓ Ang II-induced hypertension↓ cardiovascular fibrosis | Siddiquee et al []50 | |
| Apelin | Apelin-Apolipoprotein E double-knockout mice whose mutation results in reduced cardiac contractility and increased total plasma cholesterol levels | Significant increase in net NO bioavailability | Chun et al []39 | |
| Apelin-17 | Wistar rats | ↓ arterial blood pressure NO-dependent mechanism | Tatemoto et al []51 | |
| Apelin-12 structural analogue | Isolated Wistar rat hearts previously subjected to global ischemia and subsequently reperfused | ↑ endothelial NO synthase and NO production – vasodilation and reduction of the infarct area | Pisarenko et al []54 | |
| Apelin-13 | Isolated human preadipocytes | ↓ production of antioxidants↓ reactive oxygen species | Than et al []57 | |
| Apelin-13 | C57BL/6J mice | ↑ progenitor cells↑ angiogenesis↑ density of the myocardial capillaries↑ arteriole formation↓ myocardial apoptosis | Li et al []58 | |
| Apelin-13 | Sprague-Dawley rats subjected to left coronary artery occlusion with subsequent reperfusion | ↓ apoptosis via PI3K and MEK1/2protection against ischemia/reperfusion injury | Tao et al []60 | |
| apelin-13 | Isolated Sprague Dawley rat hearts after 35 minutes of ischemia and 120 minutes of reperfusion | ↓ infarct size | Kleinz et al []61 | |
| Apelin-13 | Naïve mouse cardiac fibroblasts with apelin | ↓ collagen production↓ endothelial proliferation | Pchejetski et al []62 | |
| Apelin-12 | Isolated cardiac fibroblasts of C57BL/6J mice | ↓ fibrotic responses in cardiac fibroblasts↓ transformation into myofibroblasts | Falcão-Pires et al []7 | |
| Apelin-13 | Male C57BL/6J mice | ↓ left ventricular end diastolic area↑ heart rate↑ ventricular elastance↑ preload↑ velocity of circumferential shortening↑ cardiac output | Ashley et al []63 | |
| Apelin-16 | Activation of the of the sarcolemmal NHE in cultured neonatal rat cardiac myocytes | ↑ conduction velocity – antiarrhythmic action | Farkasfalvi et al []67 | |
| Apelin-12 | Patients with atrial fibrillation | Lower plasma concentration in patients suffering from atrial fibrillation than in the control group | Gurger 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. | ||||