TY - JOUR
T1 - Biology of proprotein convertase subtilisin kexin 9
T2 - Beyond low-density lipoprotein cholesterol lowering
AU - Norata, Giuseppe Danilo
AU - Tavori, Hagai
AU - Pirillo, Angela
AU - Fazio, Sergio
AU - Catapano, Alberico L.
N1 - Publisher Copyright:
© 2016 The Author.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted.
AB - Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted.
KW - APO B
KW - LDL
KW - LDLR
KW - Monoclonal antibodies
KW - PCSK9
UR - http://www.scopus.com/inward/record.url?scp=84992663742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992663742&partnerID=8YFLogxK
U2 - 10.1093/cvr/cvw194
DO - 10.1093/cvr/cvw194
M3 - Review article
C2 - 27496869
AN - SCOPUS:84992663742
SN - 0008-6363
VL - 112
SP - 429
EP - 442
JO - Cardiovascular research
JF - Cardiovascular research
IS - 1
ER -