Collagen-Specific HSP47+ Myofibroblasts and CD163+ Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections. J Am Heart Assoc 2023 Feb 21;12(4):e027990
Date
02/16/2023Pubmed ID
36789856Pubmed Central ID
PMC10111490DOI
10.1161/JAHA.122.027990Scopus ID
2-s2.0-85148479620 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.
Author List
Puzyrenko A, Jacobs ER, Padilla N, Devine A, Aljadah M, Gantner BN, Pan AY, Lai S, Dai Q, Rubenstein JC, North PE, Simpson PM, Willoughby RE, O'Meara CC, Flinn MA, Lough JW, Ibrahim EH, Zheng Z, Sun Y, Felix J, Hunt BC, Ross G, Rui H, Benjamin IJAuthors
Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of WisconsinQiang Dai Research Scientist I in the Medicine department at Medical College of Wisconsin
Juan Felix MD Vice Chair, Director, Professor in the Pathology department at Medical College of Wisconsin
Michael Andrew Flinn Postdoctoral Fellow in the Physiology department at Medical College of Wisconsin
Benjamin N. Gantner PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
John W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
Caitlin C. O'Meara PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Amy Y. Pan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Gracious R. Ross Research Scientist II in the Cardiovascular Center department at Medical College of Wisconsin
Jason C. Rubenstein MD Associate Professor in the Medicine department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin
Ze Zheng PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
CollagenCollagen Type I
Fibrosis
Heat-Shock Proteins
Humans
Macrophages
Myofibroblasts
Phenotype
