RESUMO
Microalgae are primary producers with multiple nutrients in aquatic environments and mostly have applications in biological feed and fuel industry. There are few studies assessing the angiotensin-I-converting enzyme (ACE) inhibition potential of Isochrysis zhanjiangensis, other than its antioxidant potential. In this study, we evaluated a peptide from I. zhanjiangensis (PIZ, FEIHCC) and its vascular endothelial factors and mechanism in human umbilical vein endothelial cells (HUVEC). The results reveal that PIZ (IC50 = 61.38 µM) acts against ACE in a non-competitive binding mode. In addition, PIZ inhibits angiotensin II (Ang II)-induced vascular factor secretion and expression by blocking inflammation and apoptosis through nuclear factor κB (NF-κB), nuclear erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), and the serine/threonine kinase (Akt) signal pathways. This study reveals that PIZ has potential to be developed as a therapeutic agent for hypertension and provides a new method of high-value utilization of I. zhanjiangensis.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Haptófitas/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Microalgas/química , Peptídeos/farmacologia , Extratos Vegetais/farmacologia , Lesões do Sistema Vascular/metabolismo , Angiotensina II/genética , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/química , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Peptídeos/química , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/química , Lesões do Sistema Vascular/tratamento farmacológico , Lesões do Sistema Vascular/genéticaRESUMO
Hypertension is recognized to be associated with low-grade inflammation. Baicalin (BAI) is reported to possess various pharmacological including anti-inflammatory activities. This research explored the molecular mechanism by which BAI functions in human aortic endothelial cells (HAECs). HAECs were pretreated with BAI. Cell viability, apoptosis, and expressions of crucial proteins were respectively evaluated using cell counting kit-8 assay, flow cytometry, and western blot. Productions of cytokines were respectively assessed employing quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Cell transfection was utilized to alter miR-145 expression. The expressions of proteins participated in JNK and p38MAPK pathways were analyzed utilizing western blot. TNF-α inducement successfully evoked inflammatory injury in HAECs, exhibiting as prominently suppressed viability, while facilitated apoptosis and productions of cytokines. However, BAI pretreatment significantly ameliorated TNF-α-triggered inflammatory injuries. Besides, miR-145 expression was markedly inhibited by TNF-α inducement, while notably elevated by BAI pretreatment. Although miR-145 overexpression had no significant influence on apoptosis, miR-145 silence observably reversed BAI pretreatment-evoked protective influences on TNF-α-induced HAECs, as well as the inhibited impacts on the levels of key proteins involved in JNK and p38MAPK pathways. This investigation illustrated that BAI relieved TNF-α-triggered injuries through upregulating miR-145 via suppressing JNK and p38MAPK pathways.
Assuntos
Aorta/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Flavonoides/farmacologia , MicroRNAs/genética , Fator de Necrose Tumoral alfa/metabolismo , Aorta/lesões , Aorta/metabolismo , Aorta/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/prevenção & controle , Células Endoteliais/metabolismo , Humanos , Inflamação/tratamento farmacológico , MicroRNAs/metabolismo , Ativação Transcricional/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/prevenção & controle , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Although current antiplatelet therapies provide potent antithrombotic effects, their efficacy is limited by a heightened risk of bleeding and failure to affect vascular remodeling after injury. New lines of research suggest that thrombosis and hemorrhage may be uncoupled at the interface of pathways controlling thrombosis and inflammation. Here, as one remarkable example, studies using a novel and highly selective pharmacologic inhibitor of the spleen tyrosine kinase Syk [PRT060318; 2-((1R,2S)-2-aminocyclohexylamino)-4-(m-tolylamino)pyrimidine-5-carboxamide] coupled with genetic experiments, demonstrate that Syk inhibition ameliorates both the acute and chronic responses to vascular injury without affecting hemostasis. Specifically, lack of Syk (murine radiation chimeras) attenuated shear-induced thrombus formation ex vivo, and PRT060318 strongly inhibited arterial thrombosis in vivo in multiple animal species while having minimal impact on bleeding. Furthermore, leukocyte-platelet-dependent responses to vascular injury, including inflammatory cell recruitment and neointima formation, were markedly inhibited by PRT060318. Thus, Syk controls acute and long-term responses to arterial vascular injury. The therapeutic potential of Syk may be exemplary of a new class of antiatherothrombotic agents that target the interface between thrombosis and inflammation.