ArticleAntioxidants & redox signaling2015
Hemodynamic shear stress via ROS modulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04338165 (Effect of Impact of PCSK9 Inhibitors on Coronary Microvascular Dysfunction in Patients With Atherosclerotic Cardiovascular Disease Proved by Myocardial Ischemia and Needing Coronarography), which is not on this map. Cited by 117 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Impact of PCSK9 Inhibitors on Coronary Microvascular Dysfunction in Patients With Atherosclerotic Cardiovascular Disease Proved by Myocardial Ischemia and Needing Coronarography : a Monocentric, Prospective, Randomized and Open-label Phase II Trial
Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.
- Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology.Cardiovascular research · 2019Guideline
- Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI.Journal of inflammation research · 2021Trial
- 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
- Unveiling novel drug targets for atherosclerosis: A Mendelian randomization analysis.Medicine · 2026Article
- Molecular mechanisms of PCSK9 in cardiology: therapeutic implications and clinical impacts on the cardiorenal axis.Molecular and cellular biochemistry · 2026Review
- LDL receptor-independent mechanisms of proprotein convertase subtilisin/kexin type 9 in cardiovascular pathophysiology.Frontiers in cardiovascular medicine · 2026Review
- Fluid Shear Stress Modulates Inflammation in Breast Cancer Microenvironment.Diseases (Basel, Switzerland) · 2025Article
- Translating the effect of dual lipid reduction with PCSK9 inhibitors on a mechanical vascular instrumental biomarker in familial hypercholesterolemia subjects.Journal of translational medicine · 2025Observational
- Article
- Endothelial Cell-Derived PCSK9 in Atherosclerosis: Pathophysiological Roles and Therapeutic Perspectives.Reviews in cardiovascular medicine · 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
- Genetic Pathogenesis of Abdominal Aortic Aneurysm and the Role of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9).Vascular specialist international · 2025Review
- 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
- Vascular leakage during circulatory failure: physiopathology, impact and treatments.Annals of intensive care · 2025Review
- PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.Molecular and cellular biochemistry · 2025Article
- CRISPR-Cas9 Targeting PCSK9: A Promising Therapeutic Approach for Atherosclerosis.Journal of cardiovascular translational research · 2025Review
- PCSK9 in Vascular Aging and Age-Related Diseases.Aging and disease · 2025Review
- PCSK9 Expression in Vascular Smooth Muscle Cells: Role of Insulin Resistance and High Glucose.International journal of molecular sciences · 2025Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsTo investigate a possible link between hemodynamic shear stress, reactive oxygen species (ROS) generation, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression.
resultsUsing a parallel-plate flow chamber, we observed that PCSK9 expression in vascular smooth muscle cells (SMCs) and endothelial cells (ECs) reached maximal value at low shear stress (3-6 dynes/cm(2)), and then began to decline with an increase in shear stress. PCSK9 expression increased when cells were treated with lipopolysaccharide. PCSK9 expression was always greater in SMCs than in ECs. ROS generation followed the same pattern as PCSK9 expression. Aortic branching and aorta-iliac bifurcation regions of mouse aorta that express low shear stress were also found to have greater PCSK9 expression (vs. other regions). To determine a relationship between ROS and PCSK9 expression, ECs and SMCs were treated with ROS inhibitors diphenylene-iodonium chloride and apocynin, and both markedly reduced PCSK9 expression. Relationship between PCSK9 and ROS was further studied in p47(phox) and gp91(phox) knockout mice; both mice strains revealed low PCSK9 levels in serum and mRNA levels in aorta-iliac bifurcation regions (vs. wild-type mice). Other studies showed that ROS and NF-κB activation plays a bridging role in PCSK9 expression via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). INNOVATION: Low shear stress induces PCSK9 expression, which is mediated by NADPH oxidase-dependent ROS production.
conclusionsThis study provides evidence that low shear stress enhances PCSK9 expression in concert with ROS generation in vascular ECs and SMCs. ROS seem to regulate PCSK9 expression. We propose that PCSK9-ROS interaction may be important in the development of atherosclerosis in arterial channels with low shear stress.
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What OpenQuestion holds
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.