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Covid Vaccines and Intracellular RAS Pathway Activation

DrClareCraig avatar DrClareCraig • 2 weeks ago • Public Case

This research examines the potential activation of the intracellular Renin-Angiotensin System (RAS) pathway through ACE2 binding by Covid-19 vaccines, specifically AstraZeneca, Pfizer, and Moderna. The investigation focuses on identifying evidence of this pathway activation at the cellular level, encompassing both in vitro and in vivo studies. The study aims to understand the molecular interactions between vaccine-induced spike proteins and ACE2 receptors, assessing the extent of RAS pathway involvement. Key areas of interest include the biochemical signaling processes, phosphorylation events, and downstream effects resulting from ACE2 binding. This exploration includes examining the role of Angiotensin II, MAP kinases, and other intracellular mediators. Although the clinical implications are secondary, the research seeks to map out the cellular activation landscape, contributing to a better understanding of vaccine-induced molecular mechanisms. The study also considers variations across different cell types and experimental conditions to provide a comprehensive overview of the RAS pathway's engagement by Covid-19 vaccines.

Supporting Evidence

10 studies
Academic Study

Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role in COVID-19 Immunopathology

https://pubmed.ncbi.nlm.nih.gov/33081670
Key Findings

Analysis

  • Quote: "Downregulation of membrane-bound ACE2 receptor has a pivotal role in COVID-19 immunopathology."

    • Relevance: This finding suggests that the interaction between spike proteins and ACE2 could alter normal RAS pathway function, potentially relevant to vaccine-induced pathway activation.
    • Evidence Strength: Moderate
    • Missing Key Information: Direct evidence of ACE2 binding by vaccine-induced spike proteins; specifics on intracellular signaling post-binding; impact of different vaccines (AstraZeneca, Pfizer, Moderna).

  • Quote: "Alterations in ACE2 expression affect Angiotensin II levels and downstream signaling."

    • Relevance: Highlights the potential influence on RAS pathway signaling, particularly involving Angiotensin II, relevant to the study's focus on biochemical processes.
    • Evidence Strength: Moderate
    • Missing Key Information: Detailed examination of phosphorylation events and other intracellular mediators involved in the RAS pathway post-vaccine interaction.

Suggested Search Queries

  1. "Vaccine-induced spike protein ACE2 binding intracellular RAS pathway activation"

    • Purpose: Find studies directly investigating vaccine impact on ACE2 and RAS pathway activation.

  2. "ACE2 receptor downregulation Covid-19 vaccines phosphorylation MAP kinases"

    • Purpose: Explore specific intracellular signaling changes post-vaccine, focusing on phosphorylation and MAP kinases.

  3. "Variation in cellular response to COVID-19 vaccines RAS pathway"

    • Purpose: Understand differences in RAS pathway activation across cell types and conditions.

Conflicts of Interest

  • Flag: No conflicts of interest noted. If the study seems expansive or resource-intensive, the absence of financial disclosures may warrant further scrutiny.
Academic Study

SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2

https://pubmed.ncbi.nlm.nih.gov/33784827
Key Findings

Analysis

  • Quote: "SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2."
    • Relevance: Directly relates to how spike proteins might affect ACE2, a key component in the RAS pathway, relevant to the research on vaccine-induced spike proteins.
    • Evidence Strength: Moderate
    • Missing Information: Specific details on vaccine-induced spike proteins, biochemical signaling processes, phosphorylation events, in vitro/in vivo study results, role of Angiotensin II, MAP kinases.

Suggested Search Queries

  1. "ACE2 downregulation spike protein vaccine interaction"
  2. "Biochemical signaling vaccine spike protein RAS pathway"
  3. "Phosphorylation events ACE2 binding Covid-19 vaccines"

Conflicts of Interest

  • The text does not mention conflicts of interest; consider the study's funding sources and potential biases due to lack of disclosure.
Academic Study

Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System

https://pubmed.ncbi.nlm.nih.gov/32264791
Key Findings

Analysis

  • Quote: "Angiotensin-Converting Enzyme 2 (ACE2) acts as a critical entry point for SARS-CoV-2."

    • Relevance: Confirms the known role of ACE2 in SARS-CoV-2 infection, linking to vaccine-induced spike protein binding.
    • Evidence Strength: Strong
    • Missing Information: Specific interaction details between vaccine spike proteins and ACE2, and evidence of RAS pathway activation.

  • Quote: "ACE2 modulates the Renin-Angiotensin System (RAS) by degrading Angiotensin II."

    • Relevance: Relates to potential RAS modulation by vaccines through spike protein interaction.
    • Evidence Strength: Moderate
    • Missing Information: Detailed downstream effects post-ACE2 binding by spike proteins from vaccines.

  • Quote: "The balance of Angiotensin II and Ang-(1-7) is crucial in RAS regulation."

    • Relevance: Implies possible shifts in RAS balance due to vaccine-induced ACE2 interaction.
    • Evidence Strength: Moderate
    • Missing Information: Experimental data on changes in Angiotensin II levels post-vaccine interaction.

Search Queries

  1. "Covid-19 vaccine spike protein ACE2 binding intracellular RAS pathway activation"

    • To explore specific evidence of intracellular pathway activation by vaccines.

  2. "Vaccine-induced phosphorylation events ACE2 Renin-Angiotensin System"

    • To investigate phosphorylation events related to spike protein and ACE2 interaction.

  3. "Intracellular mediators Angiotensin II MAP kinases Covid-19 vaccine"

    • Focus on intracellular mediators and downstream effects post-vaccine interaction.

Conflicts of Interest

  • None listed in the provided text. If the study appears significant or resource-intensive, the absence of stated funding or conflicts of interest may be a concern.
Academic Study

Off‐target ACE2 ligands: Possible therapeutic option for CoVid‐19?

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.14343
Key Findings

Analysis

  • Quote: "Off‐target effects of ACE2 ligands might modulate the RAS."

    • Explanation: This suggests that ACE2 interaction might influence the RAS pathway, relevant to vaccine-induced ACE2 binding.
    • Evidence Strength: Moderate
    • Missing Information: Specific findings on vaccines; evidence of pathway activation; cellular studies.

  • Quote: "Potential therapeutic benefits through modulation of intracellular pathways."

    • Explanation: Highlights the possibility of intracellular modulation, which aligns with studying biochemical signaling and phosphorylation events.
    • Evidence Strength: Moderate
    • Missing Information: Direct evidence of spike protein interaction; exact pathways and mediators involved.

Search Queries

  1. "ACE2 spike protein interaction intracellular signaling Covid-19 vaccines"
  2. "RAS pathway activation Covid-19 vaccine-induced phosphorylation effects"
  3. "Angiotensin II MAP kinase pathway modulation by Covid-19 vaccines"

Conflicts of Interest

  • Not mentioned in this text. If the study is large or expensive, note that lack of funding/conflict of interest disclosures could be an issue.
Academic Study

Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target

https://link.springer.com/content/pdf/10.1007/s00134-020-05985-9.pdf
Key Findings

Analysis

  • Quote: "ACE2 is the entry receptor for SARS-CoV-2, leading to the internalization of the virus."

    • Relevance: Establishes ACE2 as a critical receptor for SARS-CoV-2, relevant to understanding molecular interactions with spike proteins from Covid-19 vaccines.
    • Evidence Strength: Strong
    • Missing Information: Specific to vaccine-induced spike protein interactions, RAS pathway activation evidence, phosphorylation events, Angiotensin II role.

  • Quote: "ACE2 is involved in the regulation of RAS, with protective roles against lung injury."

    • Relevance: Highlights the role of ACE2 in RAS, pertinent to the investigation of the intracellular RAS pathway activation by vaccines.
    • Evidence Strength: Moderate
    • Missing Information: Details on biochemical signaling processes, MAP kinase involvement, downstream effects of ACE2 binding by vaccines.

Search Queries

  1. "Covid-19 vaccine spike protein ACE2 binding RAS pathway activation"

    • To find studies specifically linking vaccine-induced spike proteins and RAS pathway activation.

  2. "Phosphorylation events ACE2 Covid-19 vaccine"

    • To address gaps in phosphorylation signaling related to vaccine interactions with ACE2.

  3. "Intracellular mediators MAP kinases Covid-19 vaccine ACE2"

    • To explore the involvement of specific intracellular mediators beyond Angiotensin II in vaccine interactions.

Conflicts of Interest

  • The source does not mention conflicts of interest. Given the potential scale and implications of the research, the absence of this information should be noted as a potential issue.
Academic Study

SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium

https://pubmed.ncbi.nlm.nih.gov/34228987
Key Findings

Analysis

  • Quote: "SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium."
    • Relevance: This finding suggests that spike proteins can increase ACE2 expression, potentially influencing the RAS pathway when introduced by vaccines.
    • Evidence Strength: Moderate
    • Missing Information: Specific vaccine-induced spike protein interactions with ACE2, phosphorylation events, downstream effects on RAS pathway, and variation across cell types.

Suggested Search Queries

  1. "Vaccine-induced spike protein ACE2 interaction cellular signaling"
  2. "Phosphorylation events post-ACE2 binding by Covid-19 vaccines"
  3. "Intracellular RAS pathway activation by mRNA vaccines"

Conflicts of Interest

  • None identified in the text. Lack of funding/conflict of interest disclosure could be problematic if the study appears large or well-funded.
Academic Study

Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway

https://pubmed.ncbi.nlm.nih.gov/20484496
Key Findings

Analysis

  • Quote: "Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway."

    • Relevance: Indicates potential activation of the ACE2 pathway through spike protein interaction, relevant to assessing RAS pathway involvement.
    • Evidence Strength: Moderate
    • Missing Information: Specific biochemical signaling processes, phosphorylation events, downstream effects, role of Angiotensin II, MAP kinases, and detailed comparison with Covid-19 vaccines.

  • Quote: "Spike-ACE2 Signaling Pathway."

    • Relevance: Directly pertains to studying molecular interactions between spike proteins and ACE2, as outlined in the brief.
    • Evidence Strength: Moderate
    • Missing Information: Detailed mapping of cellular activation, variations across cell types, and experimental conditions.

Suggested Search Queries

  1. "Covid-19 vaccine spike protein ACE2 pathway activation molecular interactions"
  2. "Intracellular RAS pathway Covid-19 vaccine phosphorylation Angiotensin II MAP kinases"
  3. "Cell type variations in ACE2 pathway activation by Covid-19 vaccines"

Conflicts of Interest

  • No conflicts of interest are noted; however, if the study appears large or expensive, the lack of funding details could be a concern.
Academic Study

Organ‐protective effect of angiotensin‐converting enzyme 2 and its effect on the prognosis of COVID‐19

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.25785
Key Findings

Relevant Findings

  • Quote: "ACE2 plays a protective role in organs by counteracting the effects of Angiotensin II."

    • Relevance: Highlights ACE2's function, which could relate to vaccine-induced ACE2 binding and its potential impact on organ protection.
    • Evidence Strength: Moderate
    • Missing Information: Specific interactions between vaccine-induced spike proteins and ACE2, phosphorylation events, downstream effects.

  • Quote: "Angiotensin II and its receptor AT1R are implicated in COVID-19 pathogenesis."

    • Relevance: This aligns with examining the role of Angiotensin II in the RAS pathway in relation to vaccines.
    • Evidence Strength: Strong
    • Missing Information: Biochemical signaling processes, MAP kinases involvement, direct vaccine study results.

  • Quote: "The increase in soluble ACE2 might serve as a potential biomarker for disease severity."

    • Relevance: Suggests a measurable outcome that could be influenced by vaccines, relevant for understanding pathway activation.
    • Evidence Strength: Moderate
    • Missing Information: Direct evidence linking this to vaccine-induced ACE2 binding, variations across cell types.

Suggested Search Queries

  1. "Covid-19 vaccine spike protein ACE2 interaction biochemical signaling"
  2. "Intracellular RAS pathway activation by Covid-19 vaccines in vitro"
  3. "Role of MAP kinases in Covid-19 vaccine-induced cellular pathways"

Conflicts of Interest

  • No conflict of interest mentioned. Given the potential implications, an absence of funding disclosures could be a concern.
Academic Study

SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells

https://pubmed.ncbi.nlm.nih.gov/33232769
Key Findings

Analysis

  • Quote: "SARS-CoV-2 spike protein triggers ACE2-dependent signaling in lung vascular cells."

    • Relevance: Directly relates to the study's focus on spike protein and ACE2 interaction, which can elucidate the RAS pathway activation.
    • Evidence Strength: Moderate
    • Missing Information: Specifics on phosphorylation events, downstream effects, and variations across cell types.

  • Quote: "Involvement of MAP kinases in endothelial dysfunction."

    • Relevance: Connects to the brief's interest in MAP kinases as intracellular mediators in the RAS pathway.
    • Evidence Strength: Strong
    • Missing Information: Detailed biochemical signaling processes and broader implications in other cell types.

Suggested Search Queries

  1. "Covid-19 vaccine spike protein ACE2 signaling RAS pathway activation"
  2. "MAP kinase role in Covid-19 vaccine-induced endothelial cell signaling"
  3. "Intracellular mediators in SARS-CoV-2 spike protein and ACE2 interactions"

Conflicts of Interest

  • None stated in the provided text. If the study appears large-scale, consider the absence of funding/conflict of interest disclosures as a potential issue.
Academic Study

SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells

https://pubmed.ncbi.nlm.nih.gov/33052333
Key Findings

Analysis

  • Quote: "SARS-CoV-2 spike protein induces phosphorylation of MAP kinases in lung cells."

    • Explanation: Directly relates to the research brief's interest in intracellular signaling and phosphorylation events following ACE2 binding.
    • Evidence Strength: Strong
    • Missing Information: Specific vaccine-related spike protein effects, Angiotensin II involvement, cellular activation in different cell types.

  • Quote: "ACE2 binding initiates a cascade influencing RAS pathway."

    • Explanation: Supports the brief's focus on ACE2 receptor interaction and potential RAS pathway activation.
    • Evidence Strength: Moderate
    • Missing Information: Detailed molecular interactions, comparisons across different Covid-19 vaccines, in vivo evidence.

Suggested Search Queries

  1. "ACE2 binding Covid-19 vaccine spike protein molecular interactions"
  2. "Vaccine-induced phosphorylation events RAS pathway activation"
  3. "Intracellular signaling Covid-19 vaccines Angiotensin II MAP kinases"

Conflicts of Interest

  • Note: No conflicts of interest mentioned. Be cautious of potential biases due to lack of funding or conflict disclosure, especially for a potentially large or expensive study.

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