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Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat.

Zhang Y, Liu J, Li S, Xu RX, Sun J, Tang Y, Li JJ - BMC Cardiovasc Disord (2014)

Bottom Line: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects.Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h.We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1α, suggesting that the role of PCSK9 in myocardial injury may be needed further study.

View Article: PubMed Central - PubMed

Affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, China. tangyue1226@vip.sina.com.

ABSTRACT

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects. In addition, the pathogenesis of acute myocardial infarction (AMI) involves lipids alteration and other acute phase responses. It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The present study aimed to investigate the changes of PCSK9 concentration using AMI rat model.

Methods: AMI (n = 6-8 at each time point) or sham operated (n = 6) adult male rats model were used. Whole blood and liver tissue were collected at 1, 3, 6, 9, 12, 24, 48, and 96 hour (h) post infarction. The plasma PCSK9 concentration was measured by ELISA and lipid profiles were measured by enzymatic assay. The liver mRNA levels of PCSK9, LDLR, sterol response element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1α (HNF1α) were measured by quantitative real-time PCR.

Results: The plasma PCSK9 concentration was increased from 12 h to 96 h (P < 0.05 vs. control). Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h. Hepatic mRNA levels of LDLR, SREBP-2 and HNF1α were all increased and lipid profiles underwent great changes at this acute period.

Conclusions: We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1α, suggesting that the role of PCSK9 in myocardial injury may be needed further study.

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The mRNA expression of PCSK9 (A), LDLR (B), SREBP-2 (C) and HNF1α (D) in the liver were measured using real-time PCR. The relative ratio and standard deviation were calculated using comparative CT method (ΔΔCT value). All results were normalized against GAPDH. *P < 0.05 vs. control. PCSK9 = proprotein convertase subtilisin/kexin type 9; LDLR = low-density lipoprotein receptor; SREBP-2 = sterol regulator element–binding protein-2; HNF1α = hepatocyte nuclear factor 1α; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.
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Fig2: The mRNA expression of PCSK9 (A), LDLR (B), SREBP-2 (C) and HNF1α (D) in the liver were measured using real-time PCR. The relative ratio and standard deviation were calculated using comparative CT method (ΔΔCT value). All results were normalized against GAPDH. *P < 0.05 vs. control. PCSK9 = proprotein convertase subtilisin/kexin type 9; LDLR = low-density lipoprotein receptor; SREBP-2 = sterol regulator element–binding protein-2; HNF1α = hepatocyte nuclear factor 1α; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.

Mentions: To determine the relative mRNA expression of PCSK9 and LDLR in the liver at different time post AMI, RT-PCR was performed. As shown in Figure 2A-B, at 12 h and 24 h, the amount of PCSK9 mRNA was increased by 2.2-fold and 4.1-fold, respectively (P < 0.05 vs. control), then followed by a precipitous drop to a level similar to that of the sham group at 48 h and 96 h. Expression of the LDLR mRNA, which is known to be associated with PCSK9, was also increased by 4.7-fold at 12 h, and reached a peak level at 24 h (increased by 6.7-fold), but slightly decreased to 4.4-fold at 48 h (P < 0.05 vs. control). At 96 h, there existed no significant difference compared to the sham group.Figure 2


Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat.

Zhang Y, Liu J, Li S, Xu RX, Sun J, Tang Y, Li JJ - BMC Cardiovasc Disord (2014)

The mRNA expression of PCSK9 (A), LDLR (B), SREBP-2 (C) and HNF1α (D) in the liver were measured using real-time PCR. The relative ratio and standard deviation were calculated using comparative CT method (ΔΔCT value). All results were normalized against GAPDH. *P < 0.05 vs. control. PCSK9 = proprotein convertase subtilisin/kexin type 9; LDLR = low-density lipoprotein receptor; SREBP-2 = sterol regulator element–binding protein-2; HNF1α = hepatocyte nuclear factor 1α; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4279995&req=5

Fig2: The mRNA expression of PCSK9 (A), LDLR (B), SREBP-2 (C) and HNF1α (D) in the liver were measured using real-time PCR. The relative ratio and standard deviation were calculated using comparative CT method (ΔΔCT value). All results were normalized against GAPDH. *P < 0.05 vs. control. PCSK9 = proprotein convertase subtilisin/kexin type 9; LDLR = low-density lipoprotein receptor; SREBP-2 = sterol regulator element–binding protein-2; HNF1α = hepatocyte nuclear factor 1α; GAPDH = glyceraldehyde 3-phosphate dehydrogenase.
Mentions: To determine the relative mRNA expression of PCSK9 and LDLR in the liver at different time post AMI, RT-PCR was performed. As shown in Figure 2A-B, at 12 h and 24 h, the amount of PCSK9 mRNA was increased by 2.2-fold and 4.1-fold, respectively (P < 0.05 vs. control), then followed by a precipitous drop to a level similar to that of the sham group at 48 h and 96 h. Expression of the LDLR mRNA, which is known to be associated with PCSK9, was also increased by 4.7-fold at 12 h, and reached a peak level at 24 h (increased by 6.7-fold), but slightly decreased to 4.4-fold at 48 h (P < 0.05 vs. control). At 96 h, there existed no significant difference compared to the sham group.Figure 2

Bottom Line: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects.Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h.We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1α, suggesting that the role of PCSK9 in myocardial injury may be needed further study.

View Article: PubMed Central - PubMed

Affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, China. tangyue1226@vip.sina.com.

ABSTRACT

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects. In addition, the pathogenesis of acute myocardial infarction (AMI) involves lipids alteration and other acute phase responses. It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The present study aimed to investigate the changes of PCSK9 concentration using AMI rat model.

Methods: AMI (n = 6-8 at each time point) or sham operated (n = 6) adult male rats model were used. Whole blood and liver tissue were collected at 1, 3, 6, 9, 12, 24, 48, and 96 hour (h) post infarction. The plasma PCSK9 concentration was measured by ELISA and lipid profiles were measured by enzymatic assay. The liver mRNA levels of PCSK9, LDLR, sterol response element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1α (HNF1α) were measured by quantitative real-time PCR.

Results: The plasma PCSK9 concentration was increased from 12 h to 96 h (P < 0.05 vs. control). Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h. Hepatic mRNA levels of LDLR, SREBP-2 and HNF1α were all increased and lipid profiles underwent great changes at this acute period.

Conclusions: We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1α, suggesting that the role of PCSK9 in myocardial injury may be needed further study.

Show MeSH
Related in: MedlinePlus