Contribution of Apelin-17 to Collateral Circulation Following Cerebral Ischemic Stroke

Abstract

Apelin, an essential mediator of homeostasis, is crucially involved in cardiovascular diseases, including ischemic stroke. However, the functional roles of apelin-17 in cerebral collateral circulation and ischemic stroke protection are unknown. Here, we investigated the association between plasma apelin-17 levels and collateral circulation in patients with ischemic stroke and examined the mechanism undergirding the effects of apelin-17 on cerebral artery contraction and ischemic stroke protection in an animal model. Plasma nitric oxide (NO), apelin-17, and apelin-36 levels were assessed by enzyme-linked immunosorbent assays in ischemic stroke patients with good or poor collateral circulation and in healthy participants. Additionally, the effects of apelin-17 on rat basilar artery contractions (in vitro) and cerebral ischemia (in vivo) were determined using vessel tension measurements and nuclear magnetic resonance, respectively. Patients with good collateral circulation had significantly higher plasma apelin-17 and apelin-36 levels than both patients with poor collateral circulation and healthy participants and plasma NO levels significantly higher than those in healthy participants. In vitro, apelin-17 pretreatment markedly attenuated U46619-induced rat basilar artery contractions in an endothelium-dependent manner. Additionally, NO production or guanylyl cyclase inhibitors abolished the apelin-17 effect on U46619-induced vascular contraction. Intravenous pretreatment of rats with apelin-17 markedly reduced cerebral infarct volume at 24 h after middle cerebral artery occlusion. Plasma apelin-17 levels in ischemic stroke patients were positively associated with enhanced collateral circulation, which our animal study data suggested may have resulted from an apelin-17-induced cerebral artery dilation mediated through the NO-cGMP pathway.

Levels of Serum and Urine Catecholaminergic and Apelinergic System Members in Acute Ischemic Stroke Patients

“…NO levels in eyes with good collateral circulation were found to be higher than healthy controls, but similar to those with poor collateral circulation. 48 Elabela is involved in regulating blood pressure, fluid hemostasis, cardiac contraction and vasodilatation. Elabela performs vascular relaxation independently of NO.…”

Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke

“…This discrepancy could be due to the difference in collateral scoring technique, samples size, or blood collection time. In addition, Apelin‐17, an endogenous apelin receptor agonist which plays a role in vascular health and immune modulation (Y. Yang, Lv, et al, 2015), was positively associated with human ischemic stroke patients that had good collateral circulation (Jiang et al, 2019). Apelin can be secreted by many cell types, including endothelial cells and peripheral immune cells, and the main apelin receptor is most highly expressed on endothelial cells (Helker et al, 2020).…”

Advanced Functional Materials and Cell‐Based Therapies for the Treatment of Ischemic Stroke and Postischemic Stroke Effects

“…The presented peptide‐based nanotherapeutics can act as antioxidants,45c as inhibitors of specific ion channels and as inhibitors for chemokine heterodimer's formation . In addition, peptides can lead to functional recovery through improved circulation, enhanced angiogenesis, and finally through endogenous neural stem cells' mobilization and remyelination 44d. Peptides have also been combined with tPA,44f,g achieving the reduction of the tPA‐induced hemorrhage.…”