Effect of cilostazol on plasma levels of proprotein convertase subtilisin/kexin type 9

I. Chih Chen, Wei Kung Tseng, Yi Heng Li, Shih Ya Tseng, Ping Yen Liu, Ting Hsing Chao

Research output: Contribution to journalArticle

Abstract

The protein complex proprotein convertase subtilisin/kexin type 9 (PCSK9) serves as an important target for the prevention and treatment of atherosclerosis and lipid homeostasis. This study investigated the effect of cilostazol on plasma PCSK9 concentrations. We performed a post hoc analysis of two prospective, double-blind, randomized controlled trials including 115 patients of whom 61 received cilostazol 200 mg/day and 54 received placebo for 12 weeks. Linear regression analysis was performed to determine the associations between several parameters and changes in PCSK9 levels. Use of cilostazol, but not placebo, significantly increased plasma PCSK9 concentrations, high-density lipoprotein cholesterol levels, and number of circulating endothelial progenitor cells (EPCs), and decreased triglyceride levels with a trend toward an increase in total cholesterol (TC) levels. A reduction in hemoglobin A1C and an increase in plasma vascular endothelial growth factor and adiponectin levels with cilostazol treatment were also found. Changes in the number of circulating EPCs were positively correlated and the TC concentrations were inversely correlated with changes in the PCSK9 levels. After adjusting for changes in levels of TC and numbers of circulating EPCs and history of metabolic syndrome, use of cilostazol remained independently associated with changes in plasma PCSK9 levels. In conclusion, cilostazol treatment was significantly and independently associated with an increase in plasma PCSK9 levels in patients with peripheral artery disease or at a high risk of cardiovascular disease regardless of background statin use and caused an improvement in some metabolic disorders and levels of vasculo-angiogenic biomarkers.

Original languageEnglish
Pages (from-to)108042-108053
Number of pages12
JournalOncotarget
Volume8
Issue number64
DOIs
Publication statusPublished - 2017 Jan 1

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Cholesterol
Placebos
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Peripheral Arterial Disease
Adiponectin
cilostazol
Proprotein Convertase 9
HDL Cholesterol
Vascular Endothelial Growth Factor A
Linear Models
Atherosclerosis
Hemoglobins
Triglycerides
Homeostasis
Cardiovascular Diseases
Therapeutics
Randomized Controlled Trials
Biomarkers
Regression Analysis
Lipids

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

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abstract = "The protein complex proprotein convertase subtilisin/kexin type 9 (PCSK9) serves as an important target for the prevention and treatment of atherosclerosis and lipid homeostasis. This study investigated the effect of cilostazol on plasma PCSK9 concentrations. We performed a post hoc analysis of two prospective, double-blind, randomized controlled trials including 115 patients of whom 61 received cilostazol 200 mg/day and 54 received placebo for 12 weeks. Linear regression analysis was performed to determine the associations between several parameters and changes in PCSK9 levels. Use of cilostazol, but not placebo, significantly increased plasma PCSK9 concentrations, high-density lipoprotein cholesterol levels, and number of circulating endothelial progenitor cells (EPCs), and decreased triglyceride levels with a trend toward an increase in total cholesterol (TC) levels. A reduction in hemoglobin A1C and an increase in plasma vascular endothelial growth factor and adiponectin levels with cilostazol treatment were also found. Changes in the number of circulating EPCs were positively correlated and the TC concentrations were inversely correlated with changes in the PCSK9 levels. After adjusting for changes in levels of TC and numbers of circulating EPCs and history of metabolic syndrome, use of cilostazol remained independently associated with changes in plasma PCSK9 levels. In conclusion, cilostazol treatment was significantly and independently associated with an increase in plasma PCSK9 levels in patients with peripheral artery disease or at a high risk of cardiovascular disease regardless of background statin use and caused an improvement in some metabolic disorders and levels of vasculo-angiogenic biomarkers.",
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Effect of cilostazol on plasma levels of proprotein convertase subtilisin/kexin type 9. / Chen, I. Chih; Tseng, Wei Kung; Li, Yi Heng; Tseng, Shih Ya; Liu, Ping Yen; Chao, Ting Hsing.

In: Oncotarget, Vol. 8, No. 64, 01.01.2017, p. 108042-108053.

Research output: Contribution to journalArticle

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AU - Liu, Ping Yen

AU - Chao, Ting Hsing

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