Apelin: an antithrombotic factor that inhibits platelet function

Abstract

Key Points• Apelin plays a key role in maintaining hemostasis through the regulation of platelet function.• Treatment of platelets with apelin inhibits aggregation and thrombus formation.Apelin peptide and its receptor APJ are directly implicated in various physiological processes ranging from cardiovascular homeostasis to immune signaling. Here, we show that apelin is a key player in hemostasis with an ability to inhibit thrombin-and collagenmediated platelet activation. Mice lacking apelin displayed a shorter bleeding time and a prothrombotic profile. Their platelets exhibited increased adhesion and a reduced occlusion time in venules, and displayed a higher aggregation rate after their activation by thrombin compared with wild-type platelets. Consequently, human and mouse platelets express apelin and its receptor APJ. Apelin directly interferes with thrombin-mediated signaling pathways and platelet activation, secretion, and aggregation, but not with ADP and thromboxane A 2 -mediated pathways. IV apelin administration induced excessive bleeding and prevented thrombosis in mice. Taken together, these findings suggest that apelin and/or APJ agonists could potentially be useful adducts in antiplatelet therapies and may provide a promising perspective for patients who continue to display adverse thrombotic events with current antiplatelet therapies. (Blood. 2016;127(7):908-920)

Apelin/APJ system: A novel potential therapy target for kidney disease

“…In the cardiovascular system, apelin/APJ system can reduce blood pressure, promote the formation of new blood vessels, reduce arterial tension, and the heart preload (Yu et al, ). In addition, apelin/APJ system can regulate gastrointestinal function and insulin sensitivity, promote cell proliferation and migration, induce angiogenesis, and regulate immune function (Adam et al, ; Castan‐Laurell et al, ; Lv et al, ; Tiani et al, ; Wang et al, ; Zhou, Cao, & Chen, ). Various researches show that apelin may play a role in body fluid homeostasis (Najafipour, Soltani Hekmat, Nekooian, & Esmaeili‐Mahani, ).…”

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

“…In the cardiovascular system, apelin/ APJ can strengthen cardiac contractility, relax blood vessels and lower blood pressure (10,11). In addition, apelin/APJ can regulate gastrointestinal function and insulin sensitivity, and can promote cell proliferation, migration and angiogenesis, thus regulating immune function (12)(13)(14)(15)(16).…”

Apelin/APJ system: a novel promising therapy target for thrombotic diseases

“…Adam et al [4] recently reported that apelin/APJ receptor is expressed in human and mouse platelets. Apelin-13 inhibits a low concentration of thrombin-or collagen-induced platelet aggregation in human and mouse.…”

“…These data indicated that apelin-13 is directly involved in the regulation of platelet activation. Furthermore, Adam et al [4] also explored the antiplatelet mechanism of apelin-13 in detail. First, platelets stimulated with agonists were found to result in transient activation of integrins.…”

“…This can be explained by the existence of multiple pathways contributing to platelet activation and aggregation that are not inhibited by aspirin or P2Y12 antagonists, as in the case of thrombin-mediated pathways. Adam et al [4] demonstrated that apelin/APJ receptor inhibits thrombin-and collagen-induced platelet activation and aggregation, which reveals the new biological function of the apelin/APJ system. Apelin-13 plays antiplatelet roles mainly under the influence of integrin αIIbβ3, calcium mobilization, cGMP production, and TXA2 synthesis.…”