PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo
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-de...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/13026 |
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| author | Sai Sahana Sundararaman Linsey J. F. Peters Sumra Nazir Andrea Bonnin Marquez Janneke E. Bouma Soyolmaa Bayasgalan Yvonne Döring Emiel P. C. van der Vorst |
| author_facet | Sai Sahana Sundararaman Linsey J. F. Peters Sumra Nazir Andrea Bonnin Marquez Janneke E. Bouma Soyolmaa Bayasgalan Yvonne Döring Emiel P. C. van der Vorst |
| author_sort | Sai Sahana Sundararaman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T04:52:42Z |
| format | Article |
| id | doaj.art-cbd7e1cbb3924c838e2b83b19bbb46c2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:42Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cbd7e1cbb3924c838e2b83b19bbb46c22023-11-23T02:31:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122231302610.3390/ijms222313026PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In VivoSai Sahana Sundararaman0Linsey J. F. Peters1Sumra Nazir2Andrea Bonnin Marquez3Janneke E. Bouma4Soyolmaa Bayasgalan5Yvonne Döring6Emiel P. C. van der Vorst7Interdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, GermanyInterdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, GermanyInterdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, GermanyInterdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, GermanyInterdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, GermanyInstitute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, 80336 Munich, GermanyInstitute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, 80336 Munich, GermanyInterdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, GermanyProprotein 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.https://www.mdpi.com/1422-0067/22/23/13026PCSK9hematopoietic cellsvascular inflammationchemokine receptorssmooth muscle cellsendothelial cells |
| spellingShingle | Sai Sahana Sundararaman Linsey J. F. Peters Sumra Nazir Andrea Bonnin Marquez Janneke E. Bouma Soyolmaa Bayasgalan Yvonne Döring Emiel P. C. van der Vorst PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo International Journal of Molecular Sciences PCSK9 hematopoietic cells vascular inflammation chemokine receptors smooth muscle cells endothelial cells |
| title | PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo |
| title_full | PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo |
| title_fullStr | PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo |
| title_full_unstemmed | PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo |
| title_short | PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo |
| title_sort | pcsk9 imperceptibly affects chemokine receptor expression in vitro and in vivo |
| topic | PCSK9 hematopoietic cells vascular inflammation chemokine receptors smooth muscle cells endothelial cells |
| url | https://www.mdpi.com/1422-0067/22/23/13026 |
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