Early Use of PCSK9 Inhibitors in the Prognosis of Patients with Acute Coronary Syndrome by Protecting Vascular Endothelial Function

Linghao Xu; Yuanqi Wang; Yiqiong Wang; Liang Wang; Peizhao Du; Jing Cheng; Chunsheng Zhang; Tiantian Jiao; Lijian Xing; Md Sakibur Rahman Tapu; Haonan Jia; Jiming Li

doi:10.1159/000540083

Early Use of PCSK9 Inhibitors in the Prognosis of Patients with Acute Coronary Syndrome by Protecting Vascular Endothelial Function

Pharmacology. 2025;110(1):1-14. doi: 10.1159/000540083. Epub 2024 Jul 17.

Authors

Affiliations

¹ Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Cardiology, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Department of Cardiology, East Hospital of Clinical Medical College, Nanjing Medical University, Nanjing, China.
⁴ Laboratory of Molecular Neural Biology, School of Life Sciences and Institute of Systems Biology, Shanghai University, Shanghai, China.

PMID: 38964284
DOI: 10.1159/000540083

Abstract

Introduction: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has a protective effect on acute coronary syndrome (ACS). However, most studies have shown that this protective effect is based on a decrease in low-density lipoprotein cholesterol, while other mechanisms remain limited. This study aimed to determine whether PCSK9i can improve the prognosis of ACS patients by protecting endothelial function.

Methods: A total of 113 ACS patients were enrolled and randomly assigned to PCSK9i group (PCSK9i combined with statins) and control group (statins only). Blood lipids and endothelial function indicators were measured and analyzed 6 weeks before and after treatment. The effect of PCSK9i on the expression and secretion of endothelial function indicators in vascular endothelial cells were studied by cell experiments.

Results: After 6 weeks of treatment, endothelial function indicators such as nitric oxide (NO), thrombomodulin, intercellular cell adhesion molecule-1, endothelin-1, and flow-mediated vasodilation were significantly improved in PCSK9i group compared with control group. Only the changes of NO and von Willebrand factor were associated with blood lipid levels, whereas the changes of other endothelial function indicators were not significantly associated with blood lipid levels. PCSK9i reduced the incidence of major adverse cardiovascular events in patients with ACS compared to those in the control group. In cell experiments, PCSK9i treatment significantly ameliorated LPS induced endothelial injury in HUVECs.

Conclusion: PCSK9i can protect vascular endothelial function partly independently of its lipid-lowering effect and ameliorate the prognosis of patients with ACS within 6 weeks. This mechanism may involve heat shock transcription factor 1/heat shock proteins -related signaling pathways. Early use of PCSK9i in patients with ACS should be strongly considered in clinical practice.

Keywords: Acute coronary syndrome; Endothelial function; Prognosis; Proprotein convertase subtilisin/kexin type 9 inhibitor.

Publication types

Randomized Controlled Trial

MeSH terms

Acute Coronary Syndrome* / blood
Acute Coronary Syndrome* / diagnosis
Acute Coronary Syndrome* / drug therapy
Acute Coronary Syndrome* / physiopathology
Aged
Drug Therapy, Combination
Endothelium, Vascular* / drug effects
Endothelium, Vascular* / metabolism
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
Male
Middle Aged
Nitric Oxide / metabolism
PCSK9 Inhibitors*
Prognosis
Proprotein Convertase 9
Vasodilation / drug effects

Substances

PCSK9 Inhibitors
PCSK9 protein, human
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide
Proprotein Convertase 9