ArticleInternational journal of molecular medicine2021
PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway.
Article in International journal of molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- The Impact of PCSK9 Inhibitors on Circulatory Inflammation: Mechanisms, Evidence, and Application Prospects.JACC. Asia · 2026Review
- PCSK9 as a Potential Regulator of Endothelial Dysfunction: Mechanistic Insights and Future Directions.International journal of molecular sciences · 2026Review
- PCSK9 in vascular smooth muscle cells: biology, pathology, and inhibition to fight atherosclerosis.Atherosclerosis plus · 2026Review
- Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration.Translational vision science & technology · 2026Article
- Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- PCSK9 Inhibitors: A Potential Priority Choice for Lipid Management in Patients with Diabetic Kidney Disease.Drugs · 2025Review
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
- Mitochondrial FIS1 As a Novel Drug Target for the Treatment of Erectile Dysfunction: A Multi-Omic and Epigenomic Association Study.The world journal of men's health · 2025Article
- Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions.Biomedicines · 2025Review
- A Novel Perspective on PCSK9 in Alzheimer's Disease: A Focus on Amyloid Beta.Current medicinal chemistry · 2025Review
- PCSK9 Inhibitors and Anthracyclines: The Future of Cardioprotection in Cardio-Oncology.Hearts (Basel, Switzerland) · 2024Article
- The role of PCSK9 in heart failure and other cardiovascular diseases-mechanisms of action beyond its effect on LDL cholesterol.Heart failure reviews · 2024Review
- A novel pyroptosis-related gene signature exhibits distinct immune cells infiltration landscape in Wilms' tumor.BMC pediatrics · 2024Article
- Anti-PCSK9 Treatment Attenuates Liver Fibrosis via Inhibiting Hypoxia-Induced Autophagy in Hepatocytes.Inflammation · 2023Article
- Pyrroloquinoline quinone inhibits PCSK9-NLRP3 mediated pyroptosis of Leydig cells in obese mice.Cell death & disease · 2023Article
- Transcriptomics and metabolomics study in mouse kidney of the molecular mechanism underlying energy metabolism response to hypoxic stress in highland areas.Experimental and therapeutic medicine · 2023Article
- New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.International journal of molecular sciences · 2023Review
- PCSK9, a novel immune and ferroptosis related gene in abdominal aortic aneurysm neck.Scientific reports · 2023Article
- The role of ROS-induced pyroptosis in CVD.Frontiers in cardiovascular medicine · 2023Review
- Interactions between PCSK9 and NLRP3 inflammasome signaling in atherosclerosis.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study aimed to explore the role and mechanisms of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the oxidized low‑density lipoprotein (oxLDL)‑induced pyroptosis of vascular endothelial cells. For this purpose, human umbilical vein endothelial cells (HUVECs) were incubated with oxLDL (100 µg/ml) for 24 h to induce pyroptosis, which was detected using PI/hoechst33342 double staining. The expression of pyroptosis‑associated molecules was measured by western blot analysis and RT‑qPCR. Reactive oxygen species (ROS) and membrane potential were examined through ROS probe and JC‑1 staining, respectively. PCSK9 and mitochondrial ubiquinol‑cytochrome c reductase core protein 1 (UQCRC1) protein were knocked down by small interfering RNA (siRNA). PCSK9 was overexpressed by lentivirus. The results revealed that oxLDL induced HUVEC injury, pyroptosis and inflammatory factor release, and upregulated the expression of PCSK9 protein in the HUVECs in a concentration‑dependent manner. The silencing of PCSK9 expression with siRNA suppressed the oxLDL‑induced damage to HUVECs, the release of inflammatory substances and the occurrence of pyroptosis. In addition, oxLDL inhibited UQCRC1 expression, promoted mitochondrial membrane potential collapse and damaged mitochondrial function; however, these processes were reversed by the silencing of PCSK9. PCSK9 overexpression induced the pyroptosis of HUVECs, the generation of ROS and the disorder of mitochondrial function by inhibiting UQCRC1. Therefore, PCSK9 mediates the oxLDL‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway.
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