TY - JOUR
T1 - PCSK9 and LRP6
T2 - potential combination targets to prevent and reduce atherosclerosis
AU - Desita, Saskia R.
AU - Hariftyani, Arisvia S.
AU - Jannah, Ayik R.
AU - Setyobudi, Assyadila K.
AU - Oktaviono, Yudi H.
N1 - Funding Information:
The author would like to thank the Faculty of Medicine, Universitas Airlangga who support this study.
Publisher Copyright:
© 2022 Walter de Gruyter GmbH, Berlin/Boston 2022.
PY - 2022
Y1 - 2022
N2 - Coronary artery disease (CAD) is a disease characterized by atherosclerosis formation which causes sudden cardiac death. The prevalence of CAD is expected to increase by 2030. Atherosclerosis started from accumulation of LDL in the blood vessels, followed by endothelial cell activation and dysfunction. PCSK9 is a gene that plays an important role in the creation of atherosclerotic plaque through induced degradation of LDLRs. Inhibition of PCSK9 gene resulted in a decrease of LDLRs degradation and reduction in LDL-C levels. LRP6, as well as its mutation, is a coreceptor that contributes to atherosclerosis through the canonical Wnt/β-catenin pathway. By employing EMPs mediated miRNA-126, third-generation antisense against miR-494-3p (3 GA-494), and recombinant Wnt mouse Wnt3a (rmWnt3a), the inhibition of LRP6 could reduce VSMCs proliferation, enhancing anti-inflammatory macrophages, and diminished bioactive lipids component, respectively. Those mechanisms lead to the stabilization and reduction of atherosclerosis plaques.
AB - Coronary artery disease (CAD) is a disease characterized by atherosclerosis formation which causes sudden cardiac death. The prevalence of CAD is expected to increase by 2030. Atherosclerosis started from accumulation of LDL in the blood vessels, followed by endothelial cell activation and dysfunction. PCSK9 is a gene that plays an important role in the creation of atherosclerotic plaque through induced degradation of LDLRs. Inhibition of PCSK9 gene resulted in a decrease of LDLRs degradation and reduction in LDL-C levels. LRP6, as well as its mutation, is a coreceptor that contributes to atherosclerosis through the canonical Wnt/β-catenin pathway. By employing EMPs mediated miRNA-126, third-generation antisense against miR-494-3p (3 GA-494), and recombinant Wnt mouse Wnt3a (rmWnt3a), the inhibition of LRP6 could reduce VSMCs proliferation, enhancing anti-inflammatory macrophages, and diminished bioactive lipids component, respectively. Those mechanisms lead to the stabilization and reduction of atherosclerosis plaques.
KW - LRP6
KW - PCSK9
KW - atherosclerosis
KW - coronary heart disease
UR - http://www.scopus.com/inward/record.url?scp=85129250611&partnerID=8YFLogxK
U2 - 10.1515/jbcpp-2021-0291
DO - 10.1515/jbcpp-2021-0291
M3 - Review article
C2 - 35429418
AN - SCOPUS:85129250611
SN - 0792-6855
JO - Journal of Basic and Clinical Physiology and Pharmacology
JF - Journal of Basic and Clinical Physiology and Pharmacology
ER -