COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System shows that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrate cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with SARS-CoV-2 in the presence of interleukins, with clinical findings, to investigate plausible mechanisms of cardiac disease in COVID-19 patients. Abstract
Relates to Figure 9A. Live cell beating of hIPSC cardiomyocytes at 48hrs post infection with SARS-CoV-2. The movie has been sped up 6X and displays MSN08-06S CM line beating in the BSL3 in the following order: CM line MSN08-06S (8-48h): MOCK, Infection only at MOI 0.1, Interleukins (ILs) only (IL-6 and IL-1β each at 30ng/ml) and ILs with Infection.
Relates to Figure 10B. Normal demonstrates an apical 4-chamber view (after administration of an ultrasonic enhancing agent) from a transthoracic echocardiogram. The findings are consistent with preserved left ventricular ejection fraction and no regional wall motion abnormalities. The end-diastolic and end-systolic volumes are 104ml and 35ml, respectively with a left ventricular ejection fraction of 66%.
Relates to Figure 10C. Regional Wall Motion Abnormality (RWMA) demonstrates an apical 3-chamber view (after administration of an ultrasonic enhancing agent) from a transthoracic echocardiogram. The findings are consistent with basal and mid infero-lateral wall hypokinesis despite preserved left ventricular ejection fraction. The end-diastolic and end-systolic volumes are 102ml and 50ml, respectively with a left ventricular ejection fraction of 51%. All patients are confirmed to be COVID-19 positive and no history of cardiac disease.
Relates to Figure 10D. Diffuse demonstrates an apical 4-chamber view (after administration of an ultrasonic enhancing agent) from a transthoracic echocardiogram. The findings are consistent with diffuse left ventricular wall hypokinesis and mildly decreased left ventricular ejection fraction. The end-diastolic and end-systolic volumes are 160ml and 90ml, respectively with a left ventricular ejection fraction of 44%. All patients are confirmed to be COVID-19 positive and no history of cardiac disease.
We are a systems biology and systems pharmacology laboratory. We use systems reasoning to address fundamental questions in mammalian biology, biomedicine, and pharmacology. Our long-standing expertise is in the biochemistry and molecular biology of cell signaling pathways and networks, especially G protein pathways. We have expertise in many experimental and computational methodologies.Learn More
Patients with COVID-19 showed multiple pathophysiologies including heart kidney and clotting dysfunctions in addition to pneumonia. We do not understand the mechanisms for these varied responses. We are using single cell transcriptomic data from different human cell types representing the different organs and clinical and whole genome sequencing data from COVID-19 patients to identify genomic characteristics of susceptibility to multi-organ dysfunction.Learn More
For over two decades we have studied, both experimentally and computationally, how interactions among cell signaling networks within neurons regulate neuronal plasticity,. As part of these studies we found that memory formation processes activate transcriptional repressors that enable forgetting. We are now studying the molecular pathways and the cellular circuits within the hippocampus involved in forgetting and are determining the role of regulatory loops, such as feedforward loops, in controlling the balance between remembering and forgetting.Learn More
Chiara Mariottini, Leonardo Munari, Ellen Gunzel, Joseph M Seco, Nikos Tzavaras, Jens Hansen, Sarah A Stern, Virginia Gao, Hossein Aleyasin, Ali Sharma, Evren U Azeloglu, Georgia E Hodes , Scott J Russo , Vicki Huff , Marc R Birtwistle, Robert D Blitzer, Cristina M Alberini, Ravi Iyengar
Nat Commun. 2019 Aug 21;10(1):3756.