ArticleBiology of sex differences2021
Sex-dependent differences in the secretome of human endothelial cells.
Article in Biology of sex differences, 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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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.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Sex differences in endothelial cell biology: cellular phenotypes and molecular regulators.Frontiers in physiology · 2026Review
- Sex-specific effects of resveratrol and metformin on mitochondrial function and inflammatory activation in a TNF-α-driven human iPSC-derived endothelial dysfunction model.Frontiers in immunology · 2026Article
- Single-cell landscape of sex-specific drivers of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Fetal Bovine Serum Modulates Primary Human Cell Phenotypes, Endothelial Barrier Function, Vasculogenesis, and Angiogenesis in a Sex-Specific Manner.Cellular and molecular bioengineering · 2025Article
- Laminar Flow Alters EV Composition in HUVECs: A Study of Culture Medium Optimization and Molecular Profiling of Vesicle Cargo.Small methods · 2025Article
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Sex-dependent Pathophysiology and Therapeutic Considerations in Right Heart Disease.The Canadian journal of cardiology · 2025Review
- Extracellular Vesicles as Mediators of Endothelial Dysfunction in Cardiovascular Diseases.International journal of molecular sciences · 2025Review
- Article
- Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Sex, Endothelial Cell Functions, and Peripheral Artery Disease.International journal of molecular sciences · 2023Review
- Stratification of Amniotic Fluid Cells and Amniotic Fluid by Sex Opens Up New Perspectives on Fetal Health.Biomedicines · 2023Article
- Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial Cells.International journal of molecular sciences · 2023Article
- Sex as a Biological Variable in Tissue Engineering and Regenerative Medicine.Annual review of biomedical engineering · 2023Review
- Sex-related external factors influence pulmonary vascular angiogenesis in a sex-dependent manner.American journal of physiology. Heart and circulatory physiology · 2023Article
- Remarkable sex-specific differences at single-cell resolution in neonatal hyperoxic lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- The Effects of Silencing PTX3 on the Proteome of Human Endothelial Cells.International journal of molecular sciences · 2022Article
- Synovial single-cell heterogeneity, zonation and interactions: a patchwork of effectors in arthritis.Rheumatology (Oxford, England) · 2022Review
- An Optimized MRM-Based Workflow of the l-Arginine/Nitric Oxide Pathway Metabolites Revealed Disease- and Sex-Related Differences in the Cardiovascular Field.International journal of molecular sciences · 2022Article
- Quantitative and qualitative features of carotid and coronary atherosclerotic plaque among men and women.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCellular sex has rarely been considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and "omics" approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.
methodsWe performed proteomic and Gene Ontology (GO) analyses of the secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and Western blot techniques and efferocytosis through the ability of the macrophage cell line RAW 264.7 to engulf apoptotic ECs. PTX3 mRNA levels were measured by RT-qPCR.
resultsProteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison with female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggested that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seemed to be independent on PTX3 expression.
conclusionsOur results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.
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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.