ArticleYonsei medical journal2016
Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis.
Article in Yonsei medical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- A novel approach to combatMicrobiology spectrum · 2026Article
- Inflammatory Mechanisms in Acute Coronary Syndromes: From Pathophysiology to Therapeutic Targets.Cells · 2025Review
- Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2.Chinese journal of integrative medicine · 2024Review
- Correlation of Serum CysC, IMA, and LP-PLA2 Levels With Type 2 Diabetes Mellitus Patients With Lower Extremity Atherosclerotic Occlusive Disease.Frontiers in surgery · 2022Article
- Observational
- Inhibition of Rho-kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion.Experimental and therapeutic medicine · 2020Article
- Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery.International journal of molecular sciences · 2020Review
- Small-molecule inhibitors as potential therapeutics and as tools to understand the role of phospholipases ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIncreased 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
methodsStudies 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.
resultsThe 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 (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05).
conclusionDarapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.
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