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In a recent study published in the journal Circulation, Researchers are investigating the inflammatory response to acute respiratory distress syndrome (ARDS) within the heart.

Study: Virus-induced acute respiratory distress syndrome causes cardiomyopathy by triggering a cardiac inflammatory response. Image credit: Kateryna Kon / ShutterstockStudy: Virus-induced acute respiratory distress syndrome causes cardiomyopathy by triggering a cardiac inflammatory response. Image credit: Kateryna Kon / Shutterstock

Relationship between respiratory viral infections and CVD

Seasonal viral infections range in severity from mild flu-like symptoms to potentially fatal ARDS. For example, although coronavirus disease 2019 (COVID-19) is primarily a respiratory tract infection, it can cause ARDS and other severe cardiovascular diseases, leading to high mortality rates.

Circulating immune cells may respond to COVID-19 infection by upregulating cytokine release, which may lead to myocardial damage. Cardiac macrophages, the immune cells responsible for the myocardial inflammatory response, are increasingly being studied for their role in ARDS. Recent evidence indicates that macrophage expansion, with changes in population size and relative abundance of different cardiac macrophages, is a hallmark of ARDS.

The two main types of cardiac macrophages include CC chemokine receptor type 2 negative (CCR2).) and CCR2+ macrophage. Further studies are required to clarify the contribution of these macrophages to virus-induced cardiac outcomes.

These data will allow clinicians to make informed intervention decisions and determine whether these results are caused by the COVID-19 infection or whether the observed inflammation is due to systemic immunity to the viral infection. It will be possible to clarify whether it is a reaction or not. Additionally, this information may support the development of future treatments to prevent cardiovascular disease (CVD) after recovery from COVID-19.

About research

In this study, researchers investigated the role of viral and non-viral-induced ARDS-related immune signals in altering cardiac macrophage populations, thereby influencing CVD parameters, including systemic inflammation.

The study was conducted at Massachusetts General Hospital and included 33 control samples taken from patients who died between September and December 2019, before the onset of COVID-19, and from May 2020. The study included 21 samples taken from patients who died from coronavirus during July. -19 related complications. Samples consisted of autopsy tissue excised from the left ventricle or septal region.

at the same time, alive The study involved daily intratracheal administration of an ARDS cocktail of immunostimulants to mice, including resiquimod, imiquimod, lipopolysaccharide (LPS), and the angiotensin-converting enzyme 2 (ACE2) inhibitor MLN-4760. This model allowed the researchers to reproduce the clinical features of ARDS in mice that do not suffer from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Patient data included electrocardiograms (ECGs), echocardiography, lung computed tomography (CT) scans, blood gas analysis, temperature assessment, bronchoalveolar lavage fluid (BALF) characterization, blood pressure measurements, and flow cytometry. Contains the results. Both human and mouse necropsy samples were analyzed using ribonucleic acid (RNA) isolation, real-time polymerase chain reaction (PCR) assays, and enzyme-linked immunosorbent assays (ELISA) for measurement of protein and gene expression. Processed.

Similar immune responses in non-viral and SARS-CoV-2 associated ARDS

In the absence of viral infection, mice treated with the ARDS cocktail showed significant weight loss over the 5-day cocktail treatment period. This was accompanied by hypothermia, a common feature of both ARDS and septic shock, and the mortality rate by day 5 was over 40%.

Mice with ARDS showed bilateral opacification and immune cell infiltration within the lungs, as well as decreased blood oxygenation. Additionally, increased D-dimer, neutrophil, and monocyte levels, lower blood pressure, and lower heart rate were observed in ARDS mice. Other inflammatory pathways activated in ARDS mice include increased levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor alpha (TNF-α), and interferon-γ (IFN-γ). included. Associated with SARS-CoV-2 infection.

Increased infiltration of interstitial macrophages and decreased levels of alveolar macrophages were observed in both uninfected ARDS mice and SARS-CoV-2 infected mice. Although both mouse models showed increased levels of cardiac macrophages, this immune response was more pronounced in infected mice. Nevertheless, cardiac macrophage subsets in both models were altered to similar levels.

Comparing control myocardial samples and myocardial samples from patients with COVID-19 infection, SARS-CoV-2 infection recruits more CCR2+ CD68+ macrophages and is associated with severe infection compared to other life-threatening diseases. It was later shown to induce a strong immune response.

“Our findings indicate that systemic and myocardial inflammatory signals triggered by virus-induced ARDS may contribute to the cardiovascular complications and high mortality rate of this condition. , our study supports previous reports that SARS-CoV-2 infection increases overall macrophage numbers in the heart.” ”

Cardiac benefits of TNF-α immunotherapy

A TNF-α neutralizing antibody was also administered to mice to assess its effect on immune activation during ARDS. To this end, TNF-α immunotherapy reduced weight loss, improved body temperature, and increased blood oxygenation, leading to improved survival. Histological analysis showed that ARDS mice receiving anti-TNF-α therapy had decreased expression of macrophages, Cxcl2, IL-1β, and IL-6 in the lungs.

TNF-α therapy also improved contractile dysfunction, cardiomyocyte apoptosis, and monocyte infiltration in ARDS mice. A reduction in the total number of cardiac macrophages and the expression of IL-1β, IL-6, and TNF-α in the myocardium was also observed, demonstrating the anti-inflammatory effects associated with TNF-α immunotherapy in the lungs and hearts of ARDS mice. Ta. .

conclusion

Study results show that SARS-CoV-2 infection causes significant changes in cardiac macrophage subset levels, particularly increased levels of CCR2+ macrophages, in both mice and humans. Even in the absence of SARS-CoV-2 or other viruses, the immune response to ARDS-like insults can induce significant changes in cardiac macrophage levels, which may contribute to cardiovascular morbidity and mortality associated with ARDS. may increase.

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