Tangeretin regulates platelet function through inhibition of phosphoinositide 3-Kinase and cyclic nucleotide signaling

Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517, Ali, M. S., Moraes, L. A., Sage, T., Lewis, K. R., Jones, C. I. ORCID: https://orcid.org/0000-0001-7537-1509 and Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352 (2013) Tangeretin regulates platelet function through inhibition of phosphoinositide 3-Kinase and cyclic nucleotide signaling. Arteriosclerosis Thrombosis and Vascular Biology, 33 (12). pp. 2740-2749. ISSN 1079-5642 doi: 10.1161/ATVBAHA.113.301988

Abstract/Summary

OBJECTIVE: Dietary flavonoids have long been appreciated in reducing cardiovascular disease risk factors, but their mechanisms of action are complex in nature. In this study, the effects of tangeretin, a dietary flavonoid, were explored on platelet function, signaling, and hemostasis. APPROACH AND RESULTS: Tangeretin inhibited agonist-induced human platelet activation in a concentration-dependent manner. It inhibited agonist-induced integrin αIIbβ3 inside-out and outside-in signaling, intracellular calcium mobilization, and granule secretion. Tangeretin also inhibited human platelet adhesion and subsequent thrombus formation on collagen-coated surfaces under arterial flow conditions in vitro and reduced hemostasis in mice. Further characterization to explore the mechanism by which tangeretin inhibits platelet function revealed distinctive effects of platelet signaling. Tangeretin was found to inhibit phosphoinositide 3-kinase-mediated signaling and increase cGMP levels in platelets, although phosphodiesterase activity was unaffected. Consistent with increased cGMP levels, tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein at S239. CONCLUSIONS: This study provides support for the ability and mechanisms of action of dietary flavonoids to modulate platelet signaling and function, which may affect the risk of thrombotic disease.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/34955
Identification Number/DOI	10.1161/ATVBAHA.113.301988
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Uncontrolled Keywords	blood platelets, cAMP, cGMP, tangeretin, thrombosis, haemostasis, platelets, flavonoid
Publisher	Lippincott, Williams & Wilkins
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