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Int J Mol Sci ; 22(23)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34884827

RESUMO

Proprotein convertase subtilin/kexin type 9 (PCSK9) is a protease secreted mainly by hepatocytes and in lesser quantities by intestines, pancreas, and vascular cells. Over the years, this protease has gained importance in the field of cardiovascular biology due to its regulatory action on the low-density lipoprotein receptor (LDLR). However, recently, it has also been shown that PCSK9 acts independent of LDLR to cause vascular inflammation and increase the severity of several cardiovascular disorders. We hypothesized that PCSK9 affects the expression of chemokine receptors, major mediators of inflammation, to influence cardiovascular health. However, using overexpression of PCSK9 in murine models in vivo and PCSK9 stimulation of myeloid and vascular cells in vitro did not reveal influences of PCSK9 on the expression of certain chemokine receptors that are known to be involved in the development and progression of atherosclerosis and vascular inflammation. Hence, we conclude that the inflammatory effects of PCSK9 are not associated with the here investigated chemokine receptors and additional research is required to elucidate which mechanisms mediate PCSK9 effects independent of LDLR.


Assuntos
Pró-Proteína Convertase 9/metabolismo , Receptores de Quimiocinas/metabolismo , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/veterinária , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Leucócitos/citologia , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Pró-Proteína Convertase 9/sangue , Pró-Proteína Convertase 9/genética , Receptores de Quimiocinas/genética
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