Mary Wilson
Well-known member
Published on line: 02 June 2023
Signal Transduction and Targeted Therapy (2023)8:232
https://doi.org/10.1038/s41392-023-01489-2.
Elisa Avolio 1, Prashant K. Srivastava2, Jiahui Ji2, Michele Carrabba1, Christopher T. W. Tsang 1, Yue Gu1, Anita C. Thomas 1, Kapil Gupta 3, Imre Berger3, Costanza Emanueli2 and Paolo Madeddu1 1Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, UK; 2National Heart & Lung Institute, Imperial College, London, UK and 3School of Biochemistry, University of Bristol, Bristol, UK These authors contributed equally: Elisa Avolio, Prashant K Srivastava Correspondence: Paolo Madeddu
Dear Editor,
The Coronavirus disease 2019 (COVID-19) pandemic has caused over 670 million cases and 6.7 million deaths worldwide, many of which are attributed to cardiovascular complications. Virus- induced endothelial damage, endothelial barrier dysfunction, thrombosis, and cytokine storm are implicated in heart and multi-organ failure. The prognosis is worsened by comorbidities, including diabetes and arterial hypertension, characterized by an inflammatory and pro-thrombotic milieu and upregulation of total and glycosylated Angiotensin-Converting Enzyme 2 (ACE2) in cardiomyocytes.1,2
Cardiac pericytes represent a preferential target of SARS-CoV-2 infection.3,4 These perivascular cells preserve vascular integrity through physical and paracrine crosstalk with capillary endothelial cells. Pericyte dysfunction and detachment favor the SARS-CoV-2 to spread from the bloodstream and damage the myocardium.5
SARS-CoV-2 infection starts with the engagement of the Spike (S)-protein with its cellular ACE-2 and CD147 receptors. Due to the homology with human proteins, the S-protein also acts as a natural ligand activating the ERK1/2 MAPK signaling pathway in cardiac pericytes.6,7 Some evidence suggests that the S-protein, CD147, cyclophilin, and MAPK axis are essential in triggering the cytokine storm.7 However, an in vivo demonstration of the S- protein’s direct damaging effect on cardiac pericytes is lacking.
The present study investigated the acute effects of intrave- nously injected S-protein on the heart microvasculature of otherwise healthy mice. Moreover, we analyzed the expressional changes caused by the S-protein in primary cultures of human cardiac pericytes using bulk RNA-Sequencing. Finally, the RNA- Sequencing data were cross-referenced with single-nuclei (sn)- RNA-Sequencing datasets of COVID-19 patients’ hearts to deter- mine how expressional changes after SARS-CoV-2 infection overlap with those caused by the S-protein alone.
...
https://www.nature.com/articles/s41392-023-01489-2.pdf
Signal Transduction and Targeted Therapy (2023)8:232
https://doi.org/10.1038/s41392-023-01489-2.
Elisa Avolio 1, Prashant K. Srivastava2, Jiahui Ji2, Michele Carrabba1, Christopher T. W. Tsang 1, Yue Gu1, Anita C. Thomas 1, Kapil Gupta 3, Imre Berger3, Costanza Emanueli2 and Paolo Madeddu1 1Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, UK; 2National Heart & Lung Institute, Imperial College, London, UK and 3School of Biochemistry, University of Bristol, Bristol, UK These authors contributed equally: Elisa Avolio, Prashant K Srivastava Correspondence: Paolo Madeddu
Dear Editor,
The Coronavirus disease 2019 (COVID-19) pandemic has caused over 670 million cases and 6.7 million deaths worldwide, many of which are attributed to cardiovascular complications. Virus- induced endothelial damage, endothelial barrier dysfunction, thrombosis, and cytokine storm are implicated in heart and multi-organ failure. The prognosis is worsened by comorbidities, including diabetes and arterial hypertension, characterized by an inflammatory and pro-thrombotic milieu and upregulation of total and glycosylated Angiotensin-Converting Enzyme 2 (ACE2) in cardiomyocytes.1,2
Cardiac pericytes represent a preferential target of SARS-CoV-2 infection.3,4 These perivascular cells preserve vascular integrity through physical and paracrine crosstalk with capillary endothelial cells. Pericyte dysfunction and detachment favor the SARS-CoV-2 to spread from the bloodstream and damage the myocardium.5
SARS-CoV-2 infection starts with the engagement of the Spike (S)-protein with its cellular ACE-2 and CD147 receptors. Due to the homology with human proteins, the S-protein also acts as a natural ligand activating the ERK1/2 MAPK signaling pathway in cardiac pericytes.6,7 Some evidence suggests that the S-protein, CD147, cyclophilin, and MAPK axis are essential in triggering the cytokine storm.7 However, an in vivo demonstration of the S- protein’s direct damaging effect on cardiac pericytes is lacking.
The present study investigated the acute effects of intrave- nously injected S-protein on the heart microvasculature of otherwise healthy mice. Moreover, we analyzed the expressional changes caused by the S-protein in primary cultures of human cardiac pericytes using bulk RNA-Sequencing. Finally, the RNA- Sequencing data were cross-referenced with single-nuclei (sn)- RNA-Sequencing datasets of COVID-19 patients’ hearts to deter- mine how expressional changes after SARS-CoV-2 infection overlap with those caused by the S-protein alone.
...
https://www.nature.com/articles/s41392-023-01489-2.pdf