Sulforaphane attenuates glycoprotein VI-mediated platelet mitochondrial dysfunction through up-regulating the cAMP/PKA signaling pathway in vitro and in vivo

Platelet mitochondrial dysfunction is crucial for platelet activation, atherosclerosis and thrombosis. Sulforaphane (SFN) is a dietary isothiocyanate enriched in cruciferous vegetables and possesses multiple health benefits including cardiovascular protection. This study aims to investigate whether...

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Published in:Food & function 2023-04, Vol.14 (8), p.3613-3629
Main Authors: Zhou, Xinyu, Huang, Xinhui, Wu, Chunting, Ma, Yongjie, Li, Weiqi, Hu, Jinqiu, Li, Rong, Ya, Fuli
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Arteriosclerosis
Atherosclerosis
Attenuation
Broccoli
Caspase-3
Collagen
Cyclic AMP
Cytochrome
Cytochrome c
Cytochromes
Diet
Dietary supplements
Glycoprotein VI
Glycoproteins
Humans
Hyperactivity
Hyperreactivity
Hypersensitivity
Isothiocyanates - metabolism
Isothiocyanates - pharmacology
Kinases
Membrane potential
Mice
Mice, Inbred C57BL
Mitochondria
Oxidative stress
Phosphatidylserine
Platelets
Protein kinase A
Signal Transduction
Signaling
Sulforaphane
Thromboembolism
Thrombosis
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Summary:Platelet mitochondrial dysfunction is crucial for platelet activation, atherosclerosis and thrombosis. Sulforaphane (SFN) is a dietary isothiocyanate enriched in cruciferous vegetables and possesses multiple health benefits including cardiovascular protection. This study aims to investigate whether and how SFN modulates platelet mitochondrial dysfunction and hyperactivity and . Using a series of platelet functional assays in human platelets , we found that SFN at physiological concentrations attenuated oxidative stress-dependent platelet mitochondrial dysfunction (loss of mitochondrial membrane potential), apoptosis (cytochrome release, caspase 3 activation and phosphatidylserine exposure) and activation induced by glycoprotein VI (GPVI) agonists ( , collagen and convulxin). Moreover, 12-week supplementation of SFN-enriched broccoli sprout extract (BSE, 0.06% diet) in C57BL/6J mice also attenuated GPVI-induced platelet mitochondrial dysfunction, apoptosis and hyperreactivity . Mechanistically, these inhibitory effects of SFN treatment and BSE supplementation were mainly mediated by up-regulating the cAMP/PKA pathway though decreasing phosphodiesterase 3A (PDE3A) activity. Thus, through modulating the PDE3A/cAMP/PKA signaling pathway, and attenuating platelet mitochondrial dysfunction and hyperreactivity, SFN may be a potent cardioprotective agent.
ISSN:2042-6496
2042-650X
DOI:10.1039/d2fo03958c