ArticleJACC. Basic to translational science2023
PCSK9 Promotes Hypoxia-Induced EC Pyroptosis by Regulating Smac Mitochondrion-Cytoplasm Translocation in Critical Limb Ischemia.
Article in JACC. Basic to translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- The Impact of PCSK9 Inhibitors on Circulatory Inflammation: Mechanisms, Evidence, and Application Prospects.JACC. Asia · 2026Review
- PCSK9 in Cancer: Biological Mechanisms and Implications for Therapeutic Resistance.Biomolecules · 2025Review
- A Pre-Clinical Study on the Use of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor PEP 2-8 to Mitigate Ischemic Injury in a Rat Marginal Donor Model.International journal of molecular sciences · 2025Article
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
- Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue.Chinese medicine · 2025Article
- Promoting the transition from pyroptosis to apoptosis in endothelial cells: a novel approach to alleviate methylglyoxal-induced vascular damage.Journal of translational medicine · 2025Article
- Rationale for Early Administration of PCSK9 Inhibitors in Acute Coronary Syndrome.Reviews in cardiovascular medicine · 2024Review
- Current Understanding of Cardiovascular Calcification in Patients with Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing.Journal of inflammation research · 2024Review
- PCSK9-Inhibition to Quench Vascular Injury in Chronic Limb Threatening Ischemia.JACC. Basic to translational science · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-induced endothelial cell death and impaired angiogenesis are the main pathophysiological features of critical limb ischemia. Mechanistically, proprotein convertase subtilisin/kexin type 9 (PCSK9) promoted Smac translocation from mitochondria to the cytoplasm. Inhibition of Smac release into the cytoplasm attenuated PCSK9-mediated hypoxia-induced pyroptosis. Functionally, PCSK9 overexpression impaired angiogenesis in vitro and reduced blood perfusion in mice with lower limb ischemia, but the effect was reversed by PCSK9 inhibition. This study demonstrates that PCSK9 aggravates pyroptosis by regulating Smac mitochondrion-cytoplasm translocation in the vascular endothelium, providing novel insights into PCSK9 as a potential therapeutic target in critical limb ischemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.