TY - JOUR
T1 - Cardiac pericytes mediate the remodeling response to myocardial infarction
AU - Quijada, Pearl
AU - Park, Shuin
AU - Zhao, Peng
AU - Kolluri, Kamal S.S.
AU - Wong, David
AU - Shih, Kevin D.
AU - Fang, Kai
AU - Pezhouman, Arash
AU - Wang, Lingjun
AU - Daraei, Ali
AU - Tran, Matthew D.
AU - Rathbun, Elle M.
AU - Burgos Villar, Kimberly N.
AU - Garcia-Hernandez, Maria L.
AU - Pham, Thanh T.D.
AU - Lowenstein, Charles J.
AU - Iruela-Arispe, M. Luisa
AU - Carmichael, S. Thomas
AU - Small, Eric M.
AU - Ardehali, Reza
N1 - Funding Information:
The authors are grateful for the expert technical assistance of Kim-berly Flores from the Translational Pathology Core Laboratory for help with Picrosirius red tissue imaging and the Broad Stem Cell Institute Microscopy, Flow Cytometry, and Clinical Microarray Cores at UCLA. We would also like to acknowledge assistance from the University of Rochester Medical Center Flow Cytometry Core members Matthew Cochran, Wojciech Wojciechowski, and Erika Flores Medina for histology and from Linda Callahan for assistance with confocal microscopy. This work was supported by NIH grants R25-HL145817 and U24-DK1132746 (to PQ), T32-HL69766 (to SP), T32-HL069766 (to DW), F31-HL158037 (to KNBV), R01-HL120919, R01-HL133761, and R01-HL144867 (to EMS), and R01-NS112256 (to STC and RA). Additional support was provided by the American Heart Association and a UCLA Broad Stem Cell Research Center Innovation Award (to PQ) and the New York Department of Health (NYSTEM-C32566GG, to EMS).
Funding Information:
The authors are grateful for the expert technical assistance of Kimberly Flores from the Translational Pathology Core Laboratory for help with Picrosirius red tissue imaging and the Broad Stem Cell Institute Microscopy, Flow Cytometry, and Clinical Microarray Cores at UCLA. We would also like to acknowledge assistance from the University of Rochester Medical Center Flow Cytometry Core members Matthew Cochran, Wojciech Wojciechowski, and Erika Flores Medina for histology and from Linda Callahan for assistance with confocal microscopy. This work was supported by NIH grants R25-HL145817 and U24-DK1132746 (to PQ), T32-HL69766 (to SP), T32-HL069766 (to DW), F31-HL158037 (to KNBV), R01-HL120919, R01-HL133761, and R01-HL144867 (to EMS), and R01-NS112256 (to STC and RA). Additional support was provided by the American Heart Association and a UCLA Broad Stem Cell Research Center Innovation Award (to PQ) and the New York Department of Health (NYSTEM-C32566GG, to EMS).
Publisher Copyright:
© 2023, Quijada et al.
PY - 2023/5/15
Y1 - 2023/5/15
N2 - Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4–expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.
AB - Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4–expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.
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U2 - 10.1172/JCI162188
DO - 10.1172/JCI162188
M3 - Article
C2 - 37183820
AN - SCOPUS:85159213994
SN - 0021-9738
VL - 133
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 10
M1 - e162188
ER -
