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Published on: August 28, 2018
PCSK9 Imperceptibly Affects Chemokine Receptor Expression In Vitro and In Vivo
Sai Sahana Sundararaman1,2,3, Linsey J F Peters1,2,3, Sumra Nazir1,2,3
1Interdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany.
Insights
Proprotein convertase subtilin/kexin type 9 (PCSK9) impacts cardiovascular health. This study found PCSK9 does not affect key chemokine receptors involved in vascular inflammation, suggesting alternative mechanisms for its inflammatory effects.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Proprotein convertase subtilin/kexin type 9 (PCSK9) is a protease primarily secreted by liver cells.
- PCSK9 is crucial for regulating low-density lipoprotein receptor (LDLR) levels.
- Emerging evidence suggests PCSK9 mediates cardiovascular disorders independently of LDLR, potentially via vascular inflammation.
Purpose of the Study:
- To investigate the hypothesis that PCSK9 influences cardiovascular health by affecting chemokine receptor expression.
- To determine if PCSK9 modulates the expression of specific chemokine receptors implicated in atherosclerosis and vascular inflammation.
Main Methods:
- In vivo studies involving overexpression of PCSK9 in murine models.
- In vitro experiments stimulating myeloid and vascular cells with PCSK9.
- Analysis of chemokine receptor expression following PCSK9 manipulation.
Main Results:
- Overexpression of PCSK9 in vivo did not alter the expression of investigated chemokine receptors.
- PCSK9 stimulation of myeloid and vascular cells in vitro showed no effect on these chemokine receptors.
- The study did not find a link between PCSK9 and the expression of atherosclerosis-related chemokine receptors.
Conclusions:
- The inflammatory effects of PCSK9 in cardiovascular disease are not mediated by the specific chemokine receptors examined in this study.
- Further research is necessary to identify the precise mechanisms underlying PCSK9's non-LDLR-dependent inflammatory actions.
- Elucidating these alternative pathways is critical for understanding PCSK9's role in cardiovascular pathology.
Abstract:
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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