Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Medina-Leyte, Diana Jhoseline; Domínguez‐Pérez, Mayra; Mercado, Ingrid; Villarreal-Molina, Teresa; Jacobo-Albavera, Leonor

doi:10.3390/app10030938

Cited by 148 publications

(141 citation statements)

References 172 publications

(319 reference statements)

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“…From this perspective, HUVECs derive from a rather unique tissue with distinctive properties (it is, among others, the first interface fetus/mother). Despite this unicity, HUVECs still represent the main model for studying in vitro properties of endothelium and ECs [ 69 ]. In fact, HUVECs undergo in vitro angiogenesis, produce NO, and respond to shear stress, hyperglycemia, and inflammatory stimuli, thus recapitulating human disease pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent differences in the secretome of human endothelial cells

et al. 2021

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Background Cellular 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. Methods We 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. Results Proteomic 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. Conclusions Our 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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Section: Discussionmentioning

confidence: 99%

Sex-dependent differences in the secretome of human endothelial cells

et al. 2021

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“…From this perspective, HUVECs derive from a rather unique tissue with distinctive properties (it is, among others, the rst interface fetus/mother). Despite this unicity, HUVECs still represent the main model for studying in vitro properties of endothelium and ECs [69]. In fact, HUVECs undergo in vitro angiogenesis, produce NO, and respond to shear stress, hyperglycemia, and in ammatory stimuli, thus recapitulating human disease pathophysiology.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Sex-dependent differences in the secretome of human endothelial cells

Cattaneo

Banfi

Brioschi

et al. 2020

Preprint

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Background: Cellular sex has been rarely 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.Methods: We performed proteomic and gene ontology (GO) analyses of 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. Results: Proteomic 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 to female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggests that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seems to be independent on PTX3 expression. Conclusions: Our 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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“…4 C and D). In this study, HUVECs are used instead of human aortic endothelial cells (HAECs) due to their ready availability and similar cellular characteristics to HAECs in a two-dimensional culture (42,(50)(51)(52). We found that, with donor supplement, all grafted groups showed significant enhancement of HUVEC adhesion and proliferation compared with the ungrafted controls.…”

Section: In Vitro Antiplatelet Adhesion and Ex Vivo Antithrombogenicmentioning

confidence: 99%

Bioclickable and mussel adhesive peptide mimics for engineering vascular stent surfaces

Yang

Zhao

Hao

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

112

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Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.

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Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Cited by 148 publications

References 172 publications

Sex-dependent differences in the secretome of human endothelial cells

Sex-dependent differences in the secretome of human endothelial cells

Sex-dependent differences in the secretome of human endothelial cells

Bioclickable and mussel adhesive peptide mimics for engineering vascular stent surfaces

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