Serum From COVID-19 Individuals Shockingly Found To Cause Cardiovascular-Related Proteomic Changes In ECFCs!

COVID-19 News: A study led by researchers from the University of Cadiz-Spain has found that serum from COVID-19 infected individuals, irrespective if they were asymptomatic or had mild or severe symptoms, was able to cause cardiovascular-related proteomic changes in ECFCs (endothelial colony forming cells)!


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The COVID-19 pandemic has affected millions of people worldwide, and one of the major concerns with the disease is the effect it has on the cardiovascular system as various studies and also COVID-19 News reports have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause vascular damage and thromboembolic events, leading to cardiovascular complications and long-term sequelae in many individuals.
 
Endothelial dysfunction is one of the leading effects from COVID-19 infections, and it may lead to cardiovascular complications. Despite extensive efforts in the last two years, the molecular mechanisms involved in such processes remain poorly understood.
 
The study team decided to analyze the protein changes in endothelial colony forming cells (ECFCs) exposed to the serum of COVID-19 patients.
 
The study used a label-free quantitative proteomics approach to analyze ECFCs from healthy individuals incubated ex-vivo with the serum of COVID-19 negative donors, COVID-19 asymptomatic donors at different infective stages, or hospitalized critical COVID-19 patients, followed by proteomics analysis.
 
The study team shockingly found that 590 proteins were differentially expressed in ECFCs in response to all infected serums. Predictive analysis highlighted several proteins such as CAPN5, SURF4, LAMP2, or MT-ND1, as highly discriminating features between the groups compared.
 
The protein changes observed in ECFCs correlated with viral infection, RNA metabolism, or autophagy, among others. Interestingly, 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.
 
Endothelial dysfunction plays a significant role in the pathogenesis of COVID-19, either by direct infection through SARS-CoV-2 or as a result of the activation of inflammatory leukocytes promoted by the vascular endothelium, leading to a cytokine storm responsible for systemic inflammation. Different approaches have arisen to evaluate the potential mechanisms by which SARS-CoV-2 might promote endothelial damage, from in vitro studies with human organoids and organ-on-chip platforms, to in vivo assays with animals expressing ACE2 and further infected with SARS-CoV-2.
 
This is the first study to analyze the effect of serum factors from asymptomatic to critical COVID-19 patients over endothelial colony forming cells (ECFCs) isolated from white adipose tissue of healthy adults, by application of advanced mass spectrometry (MS)-based proteomics methods.
 
ECFCs are known to promote vascular repair, and under pathological environments, ECFCs become d ysfunctional. Therefore, ECFCs may not only provide novel opportunities in identifying biomarkers of post-COVID endothelial damage but also represent an optimal candidate to tackle SARS-CoV-2 endothelial infection and a platform to evaluate therapeutic strategies against the disease.
 
The study found that the serum of COVID-19 positive individuals, asymptomatic (PCR+ or IgG+) or critical patients, promotes changes at the protein level that resemble alterations associated with endothelial dysfunction and viral infection.
 
The study team identified different proteins associated with viral infection like ACSL1, CAPN5, or STX10, and found that they were down-regulated in ECFCs after stimulation with the serum of COVID-19 positive individuals.
 
The serum of asymptomatic individuals (PCR+ or IgG+) also caused protein changes in ECFCs that correlated with mRNA surveillance or RNA transport, phagosomes, and autophagy.
 
Recent reports indicated that SARS-CoV-2 efficiently avoids the anti-viral functions of autophagy, regulating autophagy by interaction of its factors ORF3 and NSP6 with cell host autophagic factors such as WIPI2 or LAMP2 proteins.
 
The incubation of adult ECFCs with the serum factors of SARS-CoV-2 infected individuals constitutes an optimal approach to evaluate the endothelial cells response to SARS-CoV-2 depending on the severity of COVID-19 disease, in agreement with previous results. Indeed, machine learning algorithms have reported some specific proteins such as STX10, SDCBP, CAPN5, MT-ND1 or ALDH1A1 as highly discriminating proteins between the groups compared. Many proteins identified here have been associated to viral invasion, extravasation and replication, while many others provide insights of the potential mechanisms of the virus to alter the cell host machinery in its own benefit (autophagy, mitochondrial dysfunction, etc). Moreover, the serum factors of infected individuals compromised the angiogenic potential of ECFCs, while promoted changes in the endothelial cells resembling cardiovascular-related pathologies. These changes might as well explain the activation of long-term vascular sequelae after SARS-CoV-2 infection.
 
In conclusion, the study findings shed light on the potential molecular mechanisms underlying the cardiovascular complications seen in COVID-19 patients. The use of proteomic analysis allowed for the identification of specific protein changes in ECFCs exposed to the serum of COVID-19 patients, highlighting the potential involvement of viral infection, RNA metabolism, autophagy, and mitochondrial dysfunction in endothelial dysfunction and associated cardiovascular pathologies.
 
Importantly, the results of this study could have significant implications for the development of novel therapeutic strategies for the treatment of COVID-19 and its associated cardiovascular complications. For instance, the identification of proteins that play a role in viral entry and replication, such as CTSL and PTBP1, could lead to the development of new antiviral agents. Similarly, drugs that target mitochondrial dysfunction, such as COX7C and MT-ND1, could help protect the endothelium in severe forms of COVID-19.
 
Moreover, the use of ECFCs as a model system for studying COVID-19 could also have important clinical implications. Elevated levels of ECFCs have been found in 3 months post-COVID patients, suggesting that ECFCs may provide a novel opportunity for identifying biomarkers of post-COVID endothelial damage. Furthermore, as ECFCs are known to promote vascular repair, they may represent an optimal candidate for the development of new therapies aimed at restoring endothelial function in COVID-19 patients.
 
Overall, this study provides valuable insights into the molecular mechanisms underlying the cardiovascular complications seen in COVID-19 patients, and highlights the potential of ECFCs as a model system for studying the effects of SARS-CoV-2 on the endothelium. Further studies are needed to validate these findings and to develop new therapeutic strategies for the treatment of COVID-19 and its associated cardiovascular complications.
 
The study findings were published in the peer reviewed International Journal of Biological Sciences.
https://www.ijbs.com/v19p1664.htm
 
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