Mechanical unloading coupled with coronary reperfusion stimulates cardiomyocyte proliferation and prevents unloading-induced fibrosis after myocardial infarction
File(s)
Published version
Author(s)
Bello, Sean O
Singh, Charanjit
Perbellini, Filippo
Punjabi, Prakash P
Terracciano, Cesare M
Type
Journal Article
Abstract
Percutaneous left ventricular assist devices (LVADs) have become essential tools during coronary reperfusion in high-risk PCI. Significant reduction in infarct propagation is observed when mechanical unloading is coupled with reperfusion, but little is known of the effect this reduction in wall stress and extracellular matrix with LVADs has on the heart's regenerative capacity. This study investigates the effect coronary reperfusion coupled with mechanical unloading has on myocardial fibrosis, and the impact of these changes in extracellular matrix on the heart's regenerative potential. MI was induced by coronary artery ligation in Lewis rats. Hearts underwent permanent coronary ligation (AMI) or were reperfused after 90 min (AMI/R). In each group, hearts were either loaded (AMI-L or AMI/R-L) or unloaded (AMI-U or AMI/R-U). In the unloaded subgroup, the infarcted hearts were explanted after 90 min and transplanted into the abdomen of healthy recipients via heterotopic abdominal heart–lung transplantation. The recipient’s heart acted as control. Hearts were analysed on day 7. 30 hearts were studied. In the permanent ligation group, fibrosis increased in both the loaded and unloaded hearts with no significant rise in cardiomyocyte proliferation. After coronary reperfusion, no increase in fibrosis was observed with mechanical unloading but cardiomyocyte proliferation rose significantly (AMI/R-L vs AMI/R-U p = 0.0001). Cardiomyocyte proliferative rate in the loaded and unloaded hearts was 0.6% and 3.7%, respectively, after permanent ligation, and 0.5% and 10.4%, respectively, after coronary reperfusion. These data show that coronary reperfusion coupled with mechanical unloading reduces myocardial fibrosis and upregulates cardiomyocyte proliferation after myocardial infarction.
Date Issued
2026-02-01
Date Acceptance
2025-11-11
Citation
Basic Research in Cardiology, 2026, 121 (1), pp.43-57
ISSN
0300-8428
Publisher
Springer
Start Page
43
End Page
57
Journal / Book Title
Basic Research in Cardiology
Volume
121
Issue
1
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41272071
PII: 10.1007/s00395-025-01147-4
Subjects
ACTIVATION
BLOOD-FLOW
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
CELL-PROLIFERATION
CIRCULATORY SUPPORT
Fibrosis
HEART-TRANSPLANTATION
HEMODYNAMIC SUPPORT
Infarction
Life Sciences & Biomedicine
RECOVERY
Regeneration
REGENERATION
Reperfusion
Science & Technology
THERAPY
Unloading
VENTRICULAR ASSIST DEVICE
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2025-11-22