Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective
Objective: The pedicled greater omentum, when applied onto stressed hearts using omentopexy, has been shown to be protective in humans and animals. The mechanisms underlying cardioprotection using omentopexy remain elusive. This study examined whether macrophage-mediated angiogenesis accounts for th...
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Materyal Türü: | Makale |
Dil: | English |
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Elsevier
2022-06-01
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Seri Bilgileri: | JTCVS Open |
Konular: | |
Online Erişim: | http://www.sciencedirect.com/science/article/pii/S2666273622000961 |
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author | Zhi-Dong Ge, MD, PhD Riley M. Boyd, BA Connor Lantz, BA Edward B. Thorp, PhD Joseph M. Forbess, MD, MBA |
author_facet | Zhi-Dong Ge, MD, PhD Riley M. Boyd, BA Connor Lantz, BA Edward B. Thorp, PhD Joseph M. Forbess, MD, MBA |
author_sort | Zhi-Dong Ge, MD, PhD |
collection | DOAJ |
description | Objective: The pedicled greater omentum, when applied onto stressed hearts using omentopexy, has been shown to be protective in humans and animals. The mechanisms underlying cardioprotection using omentopexy remain elusive. This study examined whether macrophage-mediated angiogenesis accounts for the cardioprotective effect of omentopexy in mice. Methods: C57BL/6 mice were subjected to minimally invasive transverse aortic constriction for 6 weeks and subsequent cardio-omentopexy for 8 weeks. Control mice underwent the same surgical procedures without aortic constriction or cardio-omentopexy. Results: Transverse aortic constriction led to left ventricular concentric hypertrophy, reduced mitral E/A ratio, increased cardiomyocyte size, and myocardial fibrosis in the mice that underwent sham cardio-omentopexy surgery. The negative effects of transverse aortic constriction were prevented by cardio-omentopexy. Myocardial microvessel density was elevated in the mice that underwent aortic constriction and sham cardio-omentopexy surgery, and cardio-omentopexy further enhanced angiogenesis. Nanostring gene array analysis uncovered the activation of angiogenesis gene networks by cardio-omentopexy. Flow cytometric analysis revealed that cardio-omentopexy triggered the accumulation of cardiac MHCIIloLyve1+TimD4+ (Major histocompatibility complex class IIlow lymphatic vessel endothelial hyaluronan receptor 1+ T cell immunoglobulin and mucin domain conataining 4+) resident macrophages at the omental–cardiac interface. Intriguingly, the depletion of macrophages with clodronate-liposome resulted in the failure of cardio-omentopexy to protect the heart and promote angiogenesis. Conclusions: Cardio-omentopexy protects the heart from pressure overload-elicited left ventricular hypertrophy and dysfunction by promoting myocardial angiogenesis. Cardiac MHCIIloLyve1+TimD4+ resident macrophages play a critical role in the cardioprotective effect and angiogenesis of cardio-omentopexy. Video Abstract: |
first_indexed | 2024-12-12T17:14:42Z |
format | Article |
id | doaj.art-68c6baf6e3cd4e2f92fb15ac3daf0c4c |
institution | Directory Open Access Journal |
issn | 2666-2736 |
language | English |
last_indexed | 2024-12-12T17:14:42Z |
publishDate | 2022-06-01 |
publisher | Elsevier |
record_format | Article |
series | JTCVS Open |
spelling | doaj.art-68c6baf6e3cd4e2f92fb15ac3daf0c4c2022-12-22T00:17:48ZengElsevierJTCVS Open2666-27362022-06-0110222242Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspectiveZhi-Dong Ge, MD, PhD0Riley M. Boyd, BA1Connor Lantz, BA2Edward B. Thorp, PhD3Joseph M. Forbess, MD, MBA4The Heart Center and Cardiovascular-Thoracic Surgery, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IllThe Heart Center and Cardiovascular-Thoracic Surgery, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IllThe Heart Center and Cardiovascular-Thoracic Surgery, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IllThe Heart Center and Cardiovascular-Thoracic Surgery, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IllDepartment of Surgery, University of Maryland School of Medicine and The Children's Heart Program, University of Maryland Children's Hospital, Baltimore, Md; Address for reprints: Joseph M. Forbess, MD, MBA, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201.Objective: The pedicled greater omentum, when applied onto stressed hearts using omentopexy, has been shown to be protective in humans and animals. The mechanisms underlying cardioprotection using omentopexy remain elusive. This study examined whether macrophage-mediated angiogenesis accounts for the cardioprotective effect of omentopexy in mice. Methods: C57BL/6 mice were subjected to minimally invasive transverse aortic constriction for 6 weeks and subsequent cardio-omentopexy for 8 weeks. Control mice underwent the same surgical procedures without aortic constriction or cardio-omentopexy. Results: Transverse aortic constriction led to left ventricular concentric hypertrophy, reduced mitral E/A ratio, increased cardiomyocyte size, and myocardial fibrosis in the mice that underwent sham cardio-omentopexy surgery. The negative effects of transverse aortic constriction were prevented by cardio-omentopexy. Myocardial microvessel density was elevated in the mice that underwent aortic constriction and sham cardio-omentopexy surgery, and cardio-omentopexy further enhanced angiogenesis. Nanostring gene array analysis uncovered the activation of angiogenesis gene networks by cardio-omentopexy. Flow cytometric analysis revealed that cardio-omentopexy triggered the accumulation of cardiac MHCIIloLyve1+TimD4+ (Major histocompatibility complex class IIlow lymphatic vessel endothelial hyaluronan receptor 1+ T cell immunoglobulin and mucin domain conataining 4+) resident macrophages at the omental–cardiac interface. Intriguingly, the depletion of macrophages with clodronate-liposome resulted in the failure of cardio-omentopexy to protect the heart and promote angiogenesis. Conclusions: Cardio-omentopexy protects the heart from pressure overload-elicited left ventricular hypertrophy and dysfunction by promoting myocardial angiogenesis. Cardiac MHCIIloLyve1+TimD4+ resident macrophages play a critical role in the cardioprotective effect and angiogenesis of cardio-omentopexy. Video Abstract: http://www.sciencedirect.com/science/article/pii/S2666273622000961cardio-omentopexyangiogenesiscardiac hypertrophymacrophages |
spellingShingle | Zhi-Dong Ge, MD, PhD Riley M. Boyd, BA Connor Lantz, BA Edward B. Thorp, PhD Joseph M. Forbess, MD, MBA Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective JTCVS Open cardio-omentopexy angiogenesis cardiac hypertrophy macrophages |
title | Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective |
title_full | Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective |
title_fullStr | Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective |
title_full_unstemmed | Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective |
title_short | Cardio-omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in miceCentral MessagePerspective |
title_sort | cardio omentopexy requires a cardioprotective innate immune response to promote myocardial angiogenesis in micecentral messageperspective |
topic | cardio-omentopexy angiogenesis cardiac hypertrophy macrophages |
url | http://www.sciencedirect.com/science/article/pii/S2666273622000961 |
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