심장비대증에서 저밀도지단백수용체 연관 단백질-1의 역할 규명

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Cardiac hypertrophy is one of risk factors associated with heart failure which is the number one cause of death worldwide. Since it has been reported that α₂-macroglobulin induces cardiomyocyte hypertrophy, we hypothesized that a reduction of low density lipoprotein receptor-related protein 1 (LRP1) would decrease cardiac hypertrophy induced by catecholamines such as, phenylephrine (PE) and norepinephrine (NE). We confirmed that cell size and protein/DNA ratio were increased in PE- or NE-treated neonatal rat cardiomyocytes (NRCM). First, we observed that the expression levels of LRP1 were significantly increased in PE- or NE-treated NRCM by ~ 3 or ~ 2 folds, respectively, higher than non-treated controls. The mRNA levels of hypertrophic markers such as, ANF, BNP, β-MHC, and HPRT were also significantly increased in PE- or NE-treated NRCM. In order to investigate the role of LRP1 in cardiac hypertrophy, we silenced LRP1 by specific siRNA molecules. We could observe the ~ 70 % down-regulation of LRP1 expression and cell area were successfully rescued to normal levels in LRP1 siRNA transfected NRCM with PE or NE. The increased protein/DNA ratio by PE- or NE-treatment was also decreased to normal values in LRP1 siRNA co-treated NRCM. In addition, we observed that the LRP1 expression level was upregulated in the after 4 ~ 5 weeks of transverse aortic constriction surgery. Our results suggest that LRP1 has a critical role in catecholamine-induced cardiac hypertrophy, which might be a potential target for treatment of cardiac hypertrophy.
Alternative Title
Role of low density lipoprotein receptor-related protein 1 in cardiac hyertrophy
Alternative Author(s)
Seulki Park
일반대학원 의과학과
Table Of Contents
List of Figures 1
Abstract 2
l. Introduction 4
ll. Materials and Methods 7
ll-1. 심근세포의 분리 및 배양 7
ll-2. 심장비대증의 측정 8
ll-3. Quantitative PCR (qPCR) 8
ll-4. Western blot 9
ll-5. 심근세포에 siRNA-LRP1 처리 10
ll-6. Immunofluorescence 및 Immunocytochemistry (ICC) 10
ll-7. 심장비대증 동물모델 (TAC 모델) 11
lll. Results 12
lll-1. 카테콜아민으로 유도된 심장비대증 확인 12
lll-2. 심장비대증에서 LRP1의 발현량 변화 16
lll-3. LRP1의 억제를 통한 심장비대증 억제 21
lll-4. 심장비대증 동물모델 (TAC 모델) 25
lll-5. 심장비대증 동물모델 (TAC 모델) 에서 LRP1의 변화 29
lV. Discussion 32
V. References 35
VI. 감사의 글 42
박슬기. (2014). 심장비대증에서 저밀도지단백수용체 연관 단백질-1의 역할 규명.
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General Graduate School > 3. Theses(Master)
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