TY - JOUR
T1 - PCSK9
T2 - A Multi-Faceted Protein That Is Involved in Cardiovascular Biology
AU - Sundararaman, Sai Sahana
AU - Doring, Yvonne
AU - van Der Vorst, Emiel P. C.
N1 - Funding Information:
Funding: This research was funded by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, the DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry of Education and Research), and NWO-ZonMw Veni (91619053) to E.P.C.v.d.V.; by the DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry of Education and Research) (81X3600216) to Y.D.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7
Y1 - 2021/7
N2 - Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is secreted mostly by hepatocytes and to a lesser extent by the intestine, pancreas, kidney, adipose tissue, and vascular cells. PCSK9 has been known to interact with the low-density lipoprotein receptor (LDLR) and chaperones the receptor to its degradation. In this manner, targeting PCSK9 is a novel attractive approach to reduce hyperlipidaemia and the risk for cardiovascular diseases. Recently, it has been recognised that the effects of PCSK9 in relation to cardiovascular complications are not only LDLR related, but that various LDLR-independent pathways and processes are also influenced. In this review, the various LDLR dependent and especially independent effects of PCSK9 on the cardiovascular system are discussed, followed by an overview of related PCSK9-polymorphisms and currently available and future therapeutic approaches to manipulate PCSK9 expression.
AB - Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is secreted mostly by hepatocytes and to a lesser extent by the intestine, pancreas, kidney, adipose tissue, and vascular cells. PCSK9 has been known to interact with the low-density lipoprotein receptor (LDLR) and chaperones the receptor to its degradation. In this manner, targeting PCSK9 is a novel attractive approach to reduce hyperlipidaemia and the risk for cardiovascular diseases. Recently, it has been recognised that the effects of PCSK9 in relation to cardiovascular complications are not only LDLR related, but that various LDLR-independent pathways and processes are also influenced. In this review, the various LDLR dependent and especially independent effects of PCSK9 on the cardiovascular system are discussed, followed by an overview of related PCSK9-polymorphisms and currently available and future therapeutic approaches to manipulate PCSK9 expression.
KW - PCSK9
KW - cardiovascular disorders
KW - low density lipoprotein receptor
KW - cholesterol
KW - polymorphisms
KW - monoclonal antibodies
KW - SUBTILISIN/KEXIN TYPE 9
KW - SMOOTH-MUSCLE-CELLS
KW - OF-FUNCTION MUTATIONS
KW - MYOCARDIAL-INFARCTION
KW - LDL CHOLESTEROL
KW - FAMILIAL HYPERCHOLESTEROLEMIA
KW - MONOCLONAL-ANTIBODIES
KW - CATALYTIC DOMAIN
KW - TURKISH PATIENTS
KW - PLASMA PCSK9
U2 - 10.3390/biomedicines9070793
DO - 10.3390/biomedicines9070793
M3 - (Systematic) Review article
C2 - 34356856
SN - 2227-9059
VL - 9
JO - Biomedicines
JF - Biomedicines
IS - 7
M1 - 793
ER -