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Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis
Yonsei Medical Journal ; : 321-327, 2016.
Article in English | WPRIM | ID: wpr-147359
ABSTRACT

PURPOSE:

Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. MATERIALS AND

METHODS:

Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg.kg-1.d-1) and high-dose darapladib (50 mg.kg-1.d-1) interventions were then administered over the course of 2 weeks.

RESULTS:

The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p0.05).

CONCLUSION:

Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Oximes / Triglycerides / Benzaldehydes / C-Reactive Protein / Cholesterol / Rats, Sprague-Dawley / 1-Alkyl-2-acetylglycerophosphocholine Esterase / Dose-Response Relationship, Drug / Atherosclerosis / Rho-Associated Kinases Type of study: Prognostic study Limits: Animals Language: English Journal: Yonsei Medical Journal Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Oximes / Triglycerides / Benzaldehydes / C-Reactive Protein / Cholesterol / Rats, Sprague-Dawley / 1-Alkyl-2-acetylglycerophosphocholine Esterase / Dose-Response Relationship, Drug / Atherosclerosis / Rho-Associated Kinases Type of study: Prognostic study Limits: Animals Language: English Journal: Yonsei Medical Journal Year: 2016 Type: Article