TY - JOUR
T1 - High-Density Lipoprotein Modifications
T2 - A Pathological Consequence or Cause of Disease Progression?
AU - Marquez, Andrea Bonnin
AU - Nazir, Sumra
AU - van der Vorst, Emiel P. C.
N1 - Funding Information:
Funding: This work is supported 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), NWO-ZonMw Veni (91619053) and Else Kröner-Fresenius Stiftung (2018-A123) to E.P.C.v.d.V.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - High-density lipoprotein (HDL) is well-known for its cardioprotective effects, as it possesses anti-inflammatory, anti-oxidative, anti-thrombotic, and cytoprotective properties. Traditionally, studies and therapeutic approaches have focused on raising HDL cholesterol levels. Recently, it became evident that, not HDL cholesterol, but HDL composition and functionality, is probably a more fruitful target. In disorders, such as chronic kidney disease or cardiovascular diseases, it has been observed that HDL is modified and becomes dysfunctional. There are different modification that can occur, such as serum amyloid, an enrichment and oxidation, carbamylation, and glycation of key proteins. Additionally, the composition of HDL can be affected by changes to enzymes such as cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and phospholipid transfer protein (PLTP) or by modification to other important components. This review will highlight some main modifications to HDL and discuss whether these modifications are purely a consequential result of pathology or are actually involved in the pathology itself and have a causal role. Therefore, HDL composition may present a molecular target for the amelioration of certain diseases, but more information is needed to determine to what extent HDL modifications play a causal role in disease development.
AB - High-density lipoprotein (HDL) is well-known for its cardioprotective effects, as it possesses anti-inflammatory, anti-oxidative, anti-thrombotic, and cytoprotective properties. Traditionally, studies and therapeutic approaches have focused on raising HDL cholesterol levels. Recently, it became evident that, not HDL cholesterol, but HDL composition and functionality, is probably a more fruitful target. In disorders, such as chronic kidney disease or cardiovascular diseases, it has been observed that HDL is modified and becomes dysfunctional. There are different modification that can occur, such as serum amyloid, an enrichment and oxidation, carbamylation, and glycation of key proteins. Additionally, the composition of HDL can be affected by changes to enzymes such as cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and phospholipid transfer protein (PLTP) or by modification to other important components. This review will highlight some main modifications to HDL and discuss whether these modifications are purely a consequential result of pathology or are actually involved in the pathology itself and have a causal role. Therefore, HDL composition may present a molecular target for the amelioration of certain diseases, but more information is needed to determine to what extent HDL modifications play a causal role in disease development.
KW - high-density lipoproteins
KW - inflammation
KW - HDL modifications
KW - dysfunctional HDL
KW - APOLIPOPROTEIN-A-I
KW - ESTER TRANSFER PROTEIN
KW - SERUM AMYLOID-A
KW - LECITHIN-CHOLESTEROL ACYLTRANSFERASE
KW - MESSENGER-RNA LEVELS
KW - PARAOXONASE ACTIVITY
KW - ANTIINFLAMMATORY PROPERTIES
KW - CARDIOVASCULAR-DISEASE
KW - RHEUMATOID-ARTHRITIS
KW - NLRP3 INFLAMMASOME
U2 - 10.3390/biomedicines8120549
DO - 10.3390/biomedicines8120549
M3 - (Systematic) Review article
C2 - 33260660
SN - 2227-9059
VL - 8
JO - Biomedicines
JF - Biomedicines
IS - 12
M1 - 549
ER -