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Updated: Aug 2, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients
Lucía Beltrán-Camacho1,2, Santosh D Bhosale3, Daniel Sánchez-Morillo1,4
1Biomedicine, Biotechnology and Public Health Department, University of Cadiz, 11002 Cadiz, Spain.
Insights
COVID-19 infection impacts cardiovascular health by damaging blood vessels. This study reveals how serum from infected individuals alters endothelial cells, impairing their function and potentially leading to heart complications.
Area of Science:
- Cardiovascular Biology
- Infectious Diseases
- Proteomics
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is linked to cardiovascular complications, including vascular damage and thromboembolic events.
- Endothelial dysfunction is an early response to COVID-19, potentially causing long-term cardiovascular sequelae.
- The precise molecular mechanisms underlying COVID-19-induced endothelial dysfunction remain unclear.
Purpose of the Study:
- To investigate protein expression changes in endothelial colony-forming cells (ECFCs) upon incubation with serum from COVID-19 patients.
- To identify molecular players involved in COVID-19-related endothelial dysfunction and cardiovascular pathologies.
- To assess the impact of COVID-19 serum on the angiogenic potential of ECFCs.
Main Methods:
- Utilized a label-free quantitative proteomics approach to analyze protein alterations in ECFCs.
- Incubated ECFCs from healthy donors ex-vivo with serum from four groups: COVID-19 negative, asymptomatic (PCR+/IgG- and PCR-/IgG+), and critical hospitalized patients.
- Performed proteomics analysis to identify differentially expressed proteins.
Main Results:
- Identified 590 differentially expressed proteins in ECFCs exposed to infected serums.
- Highlighted specific proteins (e.g., CAPN5, SURF4, LAMP2, MT-ND1) as key discriminators between patient groups.
- Observed impaired angiogenic potential of ECFCs and identified protein alterations associated with cardiovascular pathologies, particularly in response to critical patient serum.
Conclusions:
- COVID-19 serum significantly alters ECFC protein profiles, with distinct changes observed between asymptomatic and critical cases.
- Protein alterations are linked to viral infection, RNA metabolism, and autophagy pathways.
- These molecular changes contribute to endothelial dysfunction and impaired angiogenesis, highlighting a mechanism for COVID-19-associated cardiovascular complications.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly affects the cardiovascular system, causing vascular damage and thromboembolic events in critical patients. Endothelial dysfunction represents one of the first steps in response to COVID-19 that might lead to cardiovascular complications and long-term sequelae. However, despite the enormous efforts in the last two years, the molecular mechanisms involved in such processes remain poorly understood. Herein, we analyzed the protein changes taking place in endothelial colony forming cells (ECFCs) after the incubation with the serum from individuals infected with COVID-19, whether asymptomatic or critical patients, by application of a label free-quantitative proteomics approach. Specifically, ECFCs from healthy individuals were incubated ex-vivo with the serum of either COVID-19 negative donors (PCR-/IgG-, n:8), COVID-19 asymptomatic donors at different infective stages (PCR+/ IgG-, n:8and PCR-/IgG+, n:8), or hospitalized critical COVID-19 patients (n:8), followed by proteomics analysis. In total, 590 proteins were differentially expressed in ECFCs in response to all infected serums. Predictive analysis highlighted several proteins like CAPN5, SURF4, LAMP2 or MT-ND1, as highly discriminating features between the groups compared. Protein changes correlated with viral infection, RNA metabolism or autophagy, among others. Remarkably, the angiogenic potential of ECFCs in response to the infected serums was impaired, and many of the protein alterations in response to the serum of critical patients were associated with cardiovascular-related pathologies.
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