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. 2020 Dec 7;11:598649. doi: 10.3389/fphys.2020.598649

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Copyright © 2020 Schlüter, Wolf and Schreckenberg.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Example for extrahepatic expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and interaction between organs. In addition to hepatic expression of PCSK9, it is also expressed in heart and kidney. Triggered by stress, heart, and kidney can release PCSK9 and cytokines that affect hepatic expression. The combined effect of locally and systemically increased PCSK9 stresses the heart (via p38 MAP kinase activation), the kidney [via low-density lipoprotein (LDL) receptor (LDL-R) downregulation and impairment of metabolism] increases the level of LDL cholesterol (LDL-C) and oxidized LDL (oxLDL) via hepatic induction of PCSK9 that finally adds additional stress to the heart and kidney.