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Elevation in cAMP triggers intracellular signalling events and regulates a wide variety of cellular activities. Thus, we evaluated the effects of Iloprost on platelet function and apoptosis and in\u00a0vivo haemostasis and thrombosis, as well as the underlying mechanisms. Firstly, we showed that Iloprost concentration\u2010dependently inhibited agonist\u2010induced P\u2010selectin exposure, integrin \u03b1IIb\u03b23 activation, platelet aggregation, ATP release, platelet spreading, and clot retraction. Moreover, Iloprost dose\u2010dependently inhibited FeCl<jats:sub>3<\/jats:sub>\u2010induced mouse mesenteric arteriole thrombosis and markedly prolonged the tail bleeding time. Iloprost also concentration\u2010dependently inhibited mitochondrial membrane potential (\u0394\u03a8m) depolarisation and phosphatidylserine (PS) externalisation in platelets, thereby inhibiting platelet apoptosis, and Iloprost at concentrations lower than 2\u2009nM inhibited only platelet apoptosis but not platelet function. Importantly, Iloprost at low doses markedly elevated peripheral platelet counts in GPIb\u03b1 antibody\u2010induced immune thrombocytopenia (ITP). Mechanistic studies showed that Iloprost concentration\u2010dependently antagonised agonist\u2010induced decline of protein kinase A (PKA) activity and elevation of cytoplasmic Ca<jats:sup>2+<\/jats:sup> in platelets, thereby attenuating platelet activation and aggregation. Elevation in PKA activity inhibited dephosphorylation of proapoptotic protein BAD and reduced caspase\u20103 activity, thus retarding platelet apoptosis. These data demonstrate that Iloprost dose\u2010dependently inhibits platelet function and apoptosis by elevating PKA activity. Moderate\u2010dose Iloprost impairs haemostasis and thrombosis via suppression of platelet function, and low\u2010dose Iloprost elevates peripheral platelet levels by inhibiting platelet apoptosis while having no effects on platelet function.<\/jats:p>","DOI":"10.1111\/jcmm.70403","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T07:31:44Z","timestamp":1739259104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Iloprost Concentration\u2010Dependently Attenuates Platelet Function and Apoptosis by Elevating PKA Activity"],"prefix":"10.1111","volume":"29","author":[{"given":"Xuexiang","family":"Wang","sequence":"first","affiliation":[{"name":"Cyrus Tang Medical Institute, Suzhou Medical College, Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Key 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