Grune, Jana and Bajpai, Geetika and Ocak, Pervin Tuelin and Kaufmann, Eva and Mentkowski, Kyle and Pabel, Steffen and Kumowski, Nina and Pulous, Fadi E. and Tran, Kim A. and Rohde, David and Zhang, Shuang and Iwamoto, Yoshiko and Wojtkiewicz, Gregory R. and Vinegoni, Claudio and Green, Ursula and Swirski, Filip K. and Stone, James R. and Lennerz, Jochen K. and Divangahi, Maziar and Hulsmans, Maarten and Nahrendorf, Matthias (2024) Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart. CIRCULATION, 150 (1). pp. 49-61. ISSN 0009-7322, 1524-4539
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND:Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and systemic inflammation.METHODS:We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 patients with COVID-19 with SARS-CoV-2-associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with ARDS induced by intratracheal instillation of Toll-like receptor ligands and an ACE2 (angiotensin-converting enzyme 2) inhibitor.RESULTS:In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2+ (C-C chemokine receptor type 2 positive) macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2+ macrophages. Treating mice exposed to virus-like ARDS with a tumor necrosis factor alpha-neutralizing antibody reduced cardiac monocytes and inflammatory MHCIIlo CCR2+ macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure.CONCLUSIONS:Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2+ macrophage subset, and the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CARDIAC MACROPHAGES; MORTALITY-RATES; HOMEOSTASIS; MECHANISMS; COVID-19; INJURY; ACE2; acute respiratory distress syndrome; CCR2; macrophage; SARS-CoV-2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Aug 2025 07:26 |
| Last Modified: | 20 Aug 2025 07:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65600 |
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