Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxi...Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.展开更多
人类白细胞分化抗原36(cluster of differentiation 36,CD36)是1种高度糖基化的双跨膜糖蛋白,参与机体的炎性反应和免疫调节,在介导免疫相关输血反应的作用机制及调节免疫细胞的功能中起着关键作用,对输血安全有重要影响,成为当前的研...人类白细胞分化抗原36(cluster of differentiation 36,CD36)是1种高度糖基化的双跨膜糖蛋白,参与机体的炎性反应和免疫调节,在介导免疫相关输血反应的作用机制及调节免疫细胞的功能中起着关键作用,对输血安全有重要影响,成为当前的研究热点。本文回顾和综合分析国内外关于CD36在输血免疫反应中的具体作用及其调控机制的研究进展,结合临床案例和实验数据,对CD36在免疫反应的病理生理机制,及其免疫介导的输血安全问题进行综述,以期为输血安全领域提供新的理论支持和实践指导,推动输血医学的进一步发展。展开更多
基金supported by the National Natural Science Foundation of China(82003451 and 82003455)Yunnan Fundamental Research Projects(202101AT070033)the Start-Up Fund for Introduction of High-level Talents to Dali University(YBS2021015).
文摘Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.
文摘人类白细胞分化抗原36(cluster of differentiation 36,CD36)是1种高度糖基化的双跨膜糖蛋白,参与机体的炎性反应和免疫调节,在介导免疫相关输血反应的作用机制及调节免疫细胞的功能中起着关键作用,对输血安全有重要影响,成为当前的研究热点。本文回顾和综合分析国内外关于CD36在输血免疫反应中的具体作用及其调控机制的研究进展,结合临床案例和实验数据,对CD36在免疫反应的病理生理机制,及其免疫介导的输血安全问题进行综述,以期为输血安全领域提供新的理论支持和实践指导,推动输血医学的进一步发展。
