The coronavirus protein activates the natural immune response and damages heart muscle cells

Highlights of the study:

  • For the first time, scientists have shown how the SARS-CoV-2 protein can damage the heart.

  • In a study evaluating mice and human heart cells, the SARS-CoV-2 protein can cause cardiac injury by inflaming heart muscle cells.

Embargo ends at 8:00 a.m. CT/9:00 a.m. ET, Monday, July 25, 2022.

(NewMediaWire) – July 25, 2022 – CHICAGO Because heart damage is common among hospitalized patients with COVID-19, many are wondering how the virus affects the heart. Now researchers have found that a protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can damage heart muscle through an inflammatory process, according to preliminary studies to be presented at the American Heart Association’s Main Cardiovascular System. Sciences Science Sessions 2022. The July 25-28 meeting in Chicago will present the latest research in basic and translational cardiovascular science.

The spike protein is found on the surface of SARS-CoV-2, the virus that causes COVID-19. The spike proteins attach to receptors called angiotensin-converting enzyme 2 (ACE2) on target cells. The spike protein helps the virus enter healthy cells, the first step in infection. In addition to infecting the lungs, the virus can spread to other organs, causing more damage to the body and causing severe infection and death in some people.

“Clinically, it is known that COVID-19 infection can cause cardiac injury, but we do not know the mechanistic details of how this occurs. What we suspect is that this protein has an unknown pathological role,” he said. Zhiqiang Lin, Ph.D., is the study’s lead author and an assistant professor at the Masonic Medical Research Institute in Utica, New York. “Our data show that a protein from SARS-CoV-2 damages the heart muscle. That’s why it’s important to get vaccinated and prevent this disease.”

“The host’s natural immunity is the first line of defense against pathogenic invasion, and cardiac muscle cells have their own natural immune mechanism. To fight viral infection, activation of the body’s immune response is necessary; however, this can impair cardiac muscle cell function, even leading to cell death and heart failure. comes,” Lin said.

The researchers investigated whether the SARS-CoV-2 protein activates the natural immune response in heart muscle cells. HCoV-NL63 is a coronavirus that infects the respiratory system without affecting the heart, but its protein uses ACE2 to mediate viral entry. They investigated the potential of the SARS-CoV-2 protein and the NL63 protein to cause heart disease. Their results showed that the SARS-CoV-2 protein activated the innate immune response in heart muscle cells and caused heart damage, but the NL63 spike protein did not.

“The fact that the SARS-CoV-2 protein activates the natural immune response may explain its high virulence compared to other coronaviruses,” Lin said. “TLR4 signaling is a key pathway that activates the body’s natural immune response, and the SARS-CoV-2 protein activates TLR4, not the common flu protein.”

To study the effects of the SARS-CoV-2 protein on the heart, the researchers cloned the SARS-CoV-2 spike protein and the NL63 protein into an AAV9 viral vector. An AAV9 viral vector was delivered to laboratory mice to activate the protein in heart muscle cells. They found that AAV9, but not NL63 protein, caused SARS-CoV-2 spike protein to cause cardiac dysfunction, hypertrophic remodeling (enlargement), and cardiac inflammation.

In laboratory tests of heart cells grown in dishes, the researchers found that the SARS-CoV-2 spike protein made heart muscle cells significantly larger than cells without either protein. “We found direct evidence that the SARS-CoV-2 protein is toxic to heart muscle cells,” Lin said.

During this study, the researchers also looked at a heart biopsy from a patient who died of inflammation due to COVID-19. They detected SARS-CoV-2 protein and TLR4 protein in heart muscle cells and other cell types. But these two proteins were absent in healthy human heart biopsies. “Once the heart is infected with SARS-CoV-2, it activates TLR4 signaling,” Lin said. “In addition to directly damaging heart muscle cells, the protein itself is highly inflammatory and may indirectly cause systemic inflammation that causes heart disease.”

ACE2 is an important enzyme that controls blood pressure. SARS-CoV-2 infection can impair the function of ACE2, which in turn leads to increased blood pressure and thereby damage to the heart. SARS-CoV-2 may also damage the heart through other unknown pathways.

“Our study provides two pieces of evidence that the SARS-CoV-2 protein does not need ACE2 to cause heart damage. First, we found that the SARS-CoV-2 protein causes heart damage in laboratory mice. Unlike ACE2 in humans, ACE2 in mice interacts with the SARS-CoV-2 protein. does not interact, so the SARS-CoV-2 spike protein did not directly disrupt the function of ACE2 and cause heart damage.Secondly, SARS-CoV-2 and NL63 coronaviruses both use ACE2 as a receptor to infect cells, SARS-CoV-2 Only the protein interacted with TLR4 and sensitized cardiac muscle cells. Therefore, our study suggests a pathological role of SARS-CoV-2 spike protein independent of ACE2,” Lin said.

This study takes the first step toward determining whether the SARS-CoV-2 protein affects the heart. Scientists now plan to study how SARS-CoV-2 proteins cause inflammation in the heart. There are two potential pathways: the first is that the spike protein is expressed in infected cardiac muscle cells and thereby directly activates the inflammasome; the second is that the spike protein of the virus is shed into the bloodstream and circulating SARS-CoV-2 proteins damage the heart.

Co-authors Caroline Sheldon, BA; Stephen Negron, BA; Chase W. Kessinger, MD; Bing Xu, MD; William T. Pu, MD; and Chie-Yu Lin, Ph.D. Authors’ statements are included in the abstract. No funding was reported for this study.

Research statements and conclusions presented at American Heart Association scientific meetings are solely those of the study authors and do not reflect the political position of the Association. The Association makes no representations or warranties as to their accuracy or reliability. Abstracts presented at the association’s scientific meetings are not peer-reviewed, rather they are curated by independent review panels and considered based on their potential to add to the diversity of scientific issues and perspectives discussed at the meeting. The results are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal. The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers, and other companies) also make charitable contributions and fund specific programs and activities of the Association. The association maintains a strict policy to ensure that these relationships do not influence the content of science. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance companies and general financial information for the Association are available here.

Additional Resources:

American Heart Association Basic Cardiovascular Sciences Scientific Sessions (BCVS) is the world’s first meeting dedicated to the latest advances in basic and translational cardiovascular science. The virtual meeting is taking place at the Chicago Hilton, July 25-28, 2022. The main goal of the meeting is to bring together scientists from around the world with the common goal of discovering new ways of cardiovascular therapy and improving cardiovascular health. Sessions will address new therapies and insights into cardiovascular disease, as well as research in areas such as microRNAs, cardiac gene and cell therapy, cardiac development, and tissue engineering and iPS cells. The American Heart Association’s Council on Basic Cardiovascular Sciences has planned a program of BCVS 2022 Scientific Sessions of special interest to basic cardiovascular scientists, molecular/cellular biologists, physiologists, translational researchers, clinical researchers, practicing cardiologists, cardiologists, and cardiologists. Follow the conference on Twitter below #BCVS22.

About the American Heart Association

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