In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. Suppl_1 ( 2022-05)
Abstract:
Background: The SARS-CoV-2 virus utilizes Angiotensin Converting Enzyme 2 (ACE2) as the functional receptor for cellular entry. Additionally, SARS-CoV-2 binding induces downregulation of the ACE2 receptor, which creates an imbalance of the ACE/ACE2 ratio that promotes thrombosis. These factors can both potentially contribute to platelet aggregation and subsequent formation of cardiovascular microvascular thrombosis that can result in cardiac failure. Thus, identification of microthrombosis and analysis of the related molecular mediators can provide further understanding of SARS-CoV-2 pathophysiology. Methods: Heart autopsy specimens (N=23) from patients who died from cardiac failure due to COVID-19 complications and control heart tissue (N=5) were collected via rapid autopsy. These samples were sectioned and stained for H & E and MOVAT. Samples were then analyzed by immunohistochemistry (IHC) to identify the following inflammatory mediators, clotting factors, and related proteins: CD42b, C1Q, SARS-CoV-2 Spike protein, SARS-CoV-2 Nucleocapsid protein, ACE2 and Thrombin. Samples were then counterstained with DAPI and visualized with an ECHO Revolve Fluorescence Microscope. ImageJ was used to analyze pixel densities of immunofluorescence patterns compared to values obtained from control samples. Results: Histological analysis with H & E and MOVAT stains demonstrated diffuse microvascular thrombosis in cardiac samples from COVID patient. IHC staining revealed the significantly increased presence of SARS-CoV-2 Spike protein (p 〈 0.0001), SARS-CoV-2 Nucleocapsid protein (p 〈 0.0001), Thrombin (p 〈 0.05), ACE2 Receptor (p 〈 0.01), CD42b (p 〈 0.01), C1Q (p 〈 0.01). Furthermore, basement membrane staining was exceptionally characteristic with CD42B and Spike protein. Conclusions: This study demonstrates the effective use of immunohistochemistry in identification of various inflammatory mediators and clotting factors involved in the vascular pathophysiology of SARS-CoV-2. Replicated studies that provide further evidence of characteristic IHC staining patterns and the presence of additional thrombus-factors would strengthen our findings and deepen the understanding of SARS-CoV-2 pathophysiology.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.42.suppl_1.255
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
1494427-3
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