PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo

Sundararaman, Sai Sahana; Peters, Linsey J. F.; Nazir, Sumra; Bonnin Marquez, Andrea; Bouma, Janneke E.; Bayasgalan, Soyolmaa; Döring, Yvonne; Van der Vorst, Emiel P. C. (2021). PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo. International journal of molecular sciences, 22(23) MDPI 10.3390/ijms222313026

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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.

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