Page 86 - ebook

[A. Biochemistry/Molecular Biology] A-43

The Regulation of PCSK9 and Wnt/β-catenin Signaling

Pathway in Myocardial Ischemic/Reperfusion Injury

Yun-Ji Cha¹ , Hyoeun Kim¹ , Sae-Bom Jeon¹, Sun-Ho Lee¹,², Seok-Min Kang³, Ho-Geun Yoon¹,²,
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Chan Joo Lee³, Seung-Hyun Lee¹, Sahng Wook Park¹,²*

¹Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 03722, Korea,

²Graduate School of Medical Science, Brain Korea 21 PLUS Project, Yonsei University College of Medicine, Seoul
03722, Korea, ³Division of Cardiology, Severance Cardiovascular Hospital, Cardiovascular Research Institute, Yonsei

University College of Medicine, Seoul 03722, Korea

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is well known as a protein that affects cholesterol homeostasis,
but recent studies have indicated that PCSK9 exerts various effects in the heart independently of LDL-cholesterol

regulation. Wnt/β-catenin signaling pathway plays a crucial role during heart development, and it is re-activated in
response to cardiac injury. Low density lipoprotein receptor-related proteins 5(LRP5), act as co-receptors of Wnt

ligands and is indispensable for Wnt signal transduction. However, it is not fully elucidated whether other members
of the LDLR-superfamily may be targets of PCSK9. Aims of this study was to determine if LDLR-related protein

5(LRP5) is a PCSK9 target and to study the association between Wnt/β-catenin signaling in myocardial ischemia. To
investigate the correlation between PCSK9 and Wnt/β-catenin signaling, Hypoxia/reoxygenation(HR) model was

established in HL-1 cells. Also, we subjected transgenic mice with cardiac-specific overexpression of PCSK9(PCSK9
TG) and wild-type mice(WT) to ischemia-reperfusion(I/R) injury induced by 1 hour of ligation of the left coronary

artery and 1 hour of reperfusion. Both in vitro and in vivo results showed that PCSK9 was significantly increased
under hypoxia. And the expression of PCSK9 decreased LRP5-related Wnt/β-catenin signaling. Our findings suggest

that PCSK9 regulates Wnt/b-catenin signaling in myocardial ischemic/reperfusion injury.