Details

Autor(en) / Beteiligte

• Rouhana, Sarah
• Jacyniak, Kathy
• Francis, Magen E
• Falzarano, Darryl
• Kelvin, Alyson A
• Pyle, W Glen

Titel

Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2023-11, Vol.325 (5), p.H1153

Ort / Verlag

United States

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection damages the heart, increasing the risk of adverse cardiovascular events. Female sex protects against complications of infection; females are less likely to experience severe illness or death, although their risk for postacute sequelae of COVID-19 ("long COVID") is higher than in males. Despite the important role of the heart in COVID-19 outcomes, molecular elements in the heart impacted by SARS-CoV-2 are poorly understood. Similarly, the role sex has on the myocardial effects of SARS-CoV-2 infection has not been investigated at a molecular level. We intranasally inoculated female and male ferrets with SARS-CoV-2 and assessed myocardial stress signals, inflammation, and the innate immune response for 14 days. Myocardial phosphorylated GSK3α/β decreased at postinfection (pi) in male ferrets, whereas females showed no changes. Myocardial levels of p62/SQSTM1 decreased in male ferrets at , , and pi while lower baseline levels in females increased on . Phosphorylated ERK1/2 increased in cardiomyocyte nuclei in females on and pi, whereas male ferrets had no changes. Only hearts from females increased fibrosis on pi. Immune and inflammation markers increased in hearts, with some sex differences. These results are the first to identify myocardial stress responses following SARS-CoV-2 infection and reveal sex differences that may contribute to differential outcomes. Future research is required to define the pathways involving these stress signals to fully understand the myocardial effects of COVID-19 and identify targets that mitigate cardiac injury following SARS-CoV-2 infection. Cardiovascular disease is a leading risk factor for severe COVID-19, and cardiovascular pathologies are among the most common adverse outcomes following SARS-CoV-2 infection. Females and males have different outcomes and adverse cardiovascular events following SARS-CoV-2 infection. This study shows sex differences in stress proteins p62/SQSTM1, ERK1/2, and GSK3α/β, along with innate immunity and inflammation in hearts of ferrets infected with SARS-CoV-2, identifying mechanisms of COVID-19 cardiac injury and cardiac complications of long COVID.