Ectopic Expression of PCSK9 by Smooth Muscle Cells Contributes to Aortic Dissection

Yasunori Iida, Hiroki Tanaka, Hideto Sano, Yuko Suzuki, Hideyuki Shimizu, Tetsumei Urano

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Acute aortic dissection (AAD) is a common disease among the elderly. Although several risk factors of AAD have been reported, the molecular mechanism underlying AAD development remains to be elucidated. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases low-density lipoprotein cholesterol levels in blood by preventing its clearance. Therefore, PCSK9 inhibition is a promising therapeutic approach to treat cardiovascular diseases (CVDs). The objective of this study was to elucidate the role of PCSK9 in the pathogenesis of AAD. Methods: We used fluorescence immunohistochemistry to assess PCSK9 expression in aortic tissues resected from 10 AAD patients and in the normal aorta from 5 autopsy samples as well as in spontaneously hyperlipidemic apolipoprotein E-deficient mice used as an experimental AD model. Results: We revealed a characteristic distribution pattern of PCSK9 in atherosclerotic plaques and the degenerated tunica media in AAD tissues, which was rarely observed in normal aortic tissues. Furthermore, PCSK9 was notably expressed around calcification areas formed by vascular smooth muscle cells, especially those of the synthetic phenotype. The results obtained in the animal model were consistent with PCSK9 expression in AAD tissues. Conclusions: Our findings suggest that PCSK9 overexpression in the aorta may promote AAD. This study adds to the growing body of evidence supporting the use of PCSK9 inhibitors for the management of CVDs.

Original languageEnglish
JournalAnnals of Vascular Surgery
DOIs
Publication statusAccepted/In press - 2017 Jan 1

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Smooth Muscle Myocytes
Dissection
Aorta
Cardiovascular Diseases
Tunica Media
Proprotein Convertase 9
Ectopic Gene Expression
Apolipoproteins E
Atherosclerotic Plaques
Vascular Smooth Muscle
LDL Cholesterol
Autopsy
Theoretical Models
Animal Models
Fluorescence
Immunohistochemistry
Phenotype

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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Ectopic Expression of PCSK9 by Smooth Muscle Cells Contributes to Aortic Dissection. / Iida, Yasunori; Tanaka, Hiroki; Sano, Hideto; Suzuki, Yuko; Shimizu, Hideyuki; Urano, Tetsumei.

In: Annals of Vascular Surgery, 01.01.2017.

Research output: Contribution to journalArticle

Iida, Yasunori ; Tanaka, Hiroki ; Sano, Hideto ; Suzuki, Yuko ; Shimizu, Hideyuki ; Urano, Tetsumei. / Ectopic Expression of PCSK9 by Smooth Muscle Cells Contributes to Aortic Dissection. In: Annals of Vascular Surgery. 2017.
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