SARS-CoV-2 Spike protein (green) staining in the pacemaker cells (red) of SARS-CoV-2 contaminated hamsters. To study SARS-CoV-2s results on pacemaker cells in more detail and with human cells, the researchers utilized advanced stem cell methods to cause human embryonic stem cells to develop into cells carefully looking like sinoatrial node cells. They revealed that these induced human pacemaker cells express the receptor ACE2 and other factors SARS-CoV-2 utilizes to get into cells and are easily infected by SARS-CoV-2. The scientists also observed large increases in inflammatory immune gene activity in the contaminated cells.
In the study, reported on March 8, 2022, in Circulation Research, the scientists utilized an animal model as well as human stem cell-derived pacemaker cells to show that SARS-CoV-2 can readily infect pacemaker cells and trigger a procedure called ferroptosis, in which the cells self-destruct but also produce reactive oxygen particles that can impact close-by cells.
” This is a unexpected and obviously unique vulnerability of these cells– we took a look at a range of other human cell types that can be contaminated by SARS-CoV-2, including even heart muscle cells, however discovered indications of ferroptosis only in the pacemaker cells,” stated study co-senior author Dr. Shuibing Chen, the Kilts Family Professor of Surgery and a teacher of chemical biology in surgery and of chemical biology in biochemistry at Weill Cornell Medicine.
Arrhythmias consisting of too-quick (tachycardia) and too-slow (bradycardia) heart rhythms have been noted amongst lots of COVID-19 patients, and several research studies have linked these unusual rhythms to even worse COVID-19 outcomes. How SARS-CoV-2 infection might trigger such arrhythmias has been uncertain.
SARS-CoV-2 Spike protein (green) staining in the pacemaker cells (red) of SARS-CoV-2 infected hamsters. The nuclei of the cells are stained blue. Credit: Dr. Shuibing Chen
In the new research study, the researchers, consisting of co-senior author Dr. Benjamin tenOever of NYU Grossman School of Medicine, analyzed golden hamsters– among the only lab animals that reliably establishes COVID-19-like indications from SARS-CoV-2 infection– and discovered evidence that following nasal direct exposure the virus can contaminate the cells of the natural heart pacemaker system, called the sinoatrial node.
To study SARS-CoV-2s results on pacemaker cells in more detail and with human cells, the researchers used sophisticated stem cell methods to induce human embryonic stem cells to develop into cells carefully resembling sinoatrial node cells. They revealed that these induced human pacemaker cells reveal the receptor ACE2 and other factors SARS-CoV-2 utilizes to get into cells and are easily contaminated by SARS-CoV-2. The researchers also observed big increases in inflammatory immune gene activity in the contaminated cells.
The teams most unexpected finding, however, was that the pacemaker cells, in action to the tension of infection, showed clear indications of a cellular self-destruct process called ferroptosis, which involves accumulation of iron and the runaway production of cell-destroying reactive oxygen molecules. The scientists had the ability to reverse these check in the cells utilizing substances that are known to bind iron and inhibit ferroptosis.
” This finding suggests that a few of the cardiac arrhythmias found in COVID-19 patients might be brought on by ferroptosis damage to the sinoatrial node,” said co-senior author Dr. Robert Schwartz, an associate professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine and a hepatologist at NewYork-Presbyterian/Weill Cornell Medical Center.
In principle COVID-19 clients could be treated with ferroptosis inhibitors specifically to safeguard sinoatrial node cells, antiviral drugs that block the effects of SARS-CoV-2 infection in all cell types would be more suitable, the scientists said.
The scientists prepare to continue to utilize their cell and animal designs to examine sinoatrial node damage in COVID-19– and beyond.
” There are other human sinoatrial arrhythmia syndromes we could model with our platform,” stated co-senior author Dr. Todd Evans, the Peter I. Pressman M.D. Professor of Surgery and associate dean for research study at Weill Cornell Medicine. “And, although doctors presently can use an artificial electronic pacemaker to change the function of a harmed sinoatrial node, theres the capacity here to utilize sinoatrial cells such as weve developed as an alternative, cell-based pacemaker therapy.”
Referral: “SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells” by Yuling Han, Jiajun Zhu, Liuliu Yang, Benjamin E. Nilsson-Payant, Romulo Hurtado, Lauretta A. Lacko, Xiaolu Sun, Aravind R. Gade, Christina A. Higgins, Whitney J. Sisso, Xue Dong, Maple Wang, Zhengming Chen, David D. Ho, Geoffrey S. Pitt, Robert E. Schwartz, Benjamin R. tenOever, Todd Evans and Shuibing Chen, 8 March 2022, Circulation Research.DOI: 10.1161/ CIRCRESAHA.121.320518.
Are COVID-19-linked arrhythmias brought on by viral damage to the hearts pacemaker cells?
The SARS-CoV-2 virus can infect customized pacemaker cells that keep the hearts balanced beat, triggering a self-destruction procedure within the cells, according to a preclinical research study co-led by scientists at Weill Cornell Medicine, NewYork-Presbyterian and NYU Grossman School of Medicine. The findings use a possible explanation for the heart arrhythmias that are commonly observed in clients with SARS-CoV-2 infection.