Objectives: The purpose of this study was to investigate the role of plasminogen (Plg) in stem cell-mediated cardiac repair and regeneration after myocardial infarction (MI).
Background: An MI induces irreversible tissue damage, eventually leading to heart failure. Bone marrow (BM)-derived stem cells promote tissue repair and regeneration after MI. Thrombolytic treatment with Plg activators significantly improves the clinical outcome in MI by restoring cardiac perfusion. However, the role of Plg in stem cell-mediated cardiac repair remains unclear.
Methods: An MI was induced in Plg-deficient (Plg(-/-)) and wild-type (Plg(+/+)) mice by ligation of the left anterior descending coronary artery. Stem cells were visualized by in vivo tracking of green fluorescent protein (GFP)-expressing BM cells after BM transplantation. Cardiac function, stem cell homing, and signaling pathways downstream of Plg were examined.
Results: Granulocyte colony-stimulating factor, a stem cell mobilizer, significantly promoted BM-derived stem cell (GFP(+)c-kit(+) cell) recruitment into the infarcted heart and stem cell-mediated cardiac repair in Plg(+/+) mice. However, Plg deficiency markedly inhibited stem cell homing and cardiac repair, suggesting that Plg is critical for stem cell-mediated cardiac repair. Moreover, Plg regulated C-X-C chemokine receptor type 4 (CXCR4) expression in stem cells in vivo and in vitro through matrix metalloproteinase-9. Lentiviral reconstitution of CXCR4 expression in BM cells successfully rescued stem cell homing to the infarcted heart in Plg-deficient mice, indicating that CXCR4 has a critical role in Plg-mediated stem cell homing after MI.
Conclusions: These findings have identified a novel role for Plg in stem cell-mediated cardiac repair after MI. Thus, targeting Plg may offer a new therapeutic strategy for stem cell-mediated cardiac repair after MI.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074457 | PMC |
| http://dx.doi.org/10.1016/j.jacc.2013.11.070 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigating the Impact of Glycogen-Depleting Exercise Combined with Prolonged Fasting on Autophagy and Cellular Health in Humans: A Randomised Controlled Crossover Trial.
Nutrients
December 2024
Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia.
Importance: Although prolonged fasting has become increasingly popular, the favourable biological adaptations and possible adverse effects in humans have yet to be fully elucidated.
Objective: To investigate the effects of a three-day water-only fasting, with or without exercise-induced glycogen depletion, on autophagy activation and the molecular pathways involved in cellular damage accumulation and repair in healthy humans.
Design: A randomised, single-centre, two-period, two-sequence crossover trial.
The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease.
Int J Mol Sci
December 2024
Pittsburgh Heart, Lung and Blood Vascular Medicine Institute (VMI), University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Matrix metalloproteinase-2 (MMP-2), a zinc-dependent enzyme, plays a critical role in the degradation and remodeling of the extracellular matrix (ECM). As a member of the gelatinase subgroup of matrix metalloproteinases, MMP-2 is involved in a variety of physiological processes, including tissue repair, wound healing, angiogenesis, and embryogenesis. It is primarily responsible for the degradation of type IV and V collagen, fibronectin, laminin, and elastin, which are essential components of the ECM.
View Article and Find Full Text PDFThe Potential of Mesenchymal Stem Cell-Derived Exosomes in Cardiac Repair.
Int J Mol Sci
December 2024
Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and effectively repairing the heart following myocardial injuries remains a significant challenge. Research has increasingly shown that exosomes derived from mesenchymal stem cells (MSC-Exo) can ameliorate myocardial injuries and improve outcomes after such injuries. The therapeutic benefits of MSC-Exo are largely due to their capacity to deliver specific cargo, including microRNAs and proteins.
View Article and Find Full Text PDFA Protocol Investigation Comparing Transcatheter Repair with the Standard Surgical Procedure for Secondary Mitral Regurgitation.
J Clin Med
December 2024
Department of Cardiac Surgery, Glenfield Hospital, University Hospitals of Leicester, Leicester LE3 9QP, UK.
Secondary mitral regurgitation (SMR) is characterized by a pathological process impacting the left ventricle (LV) as opposed to the mitral valve (MV). In the absence of structural alterations to the MV, the expansion of the LV or impairment of the papillary muscles (PMs) may ensue. A number of technical procedures are accessible for the purpose of determining the optimal resolution for MR.
View Article and Find Full Text PDFSuccessful Treatment of Unilateral Pulmonary Edema as Minimally Invasive Mitral Valve Surgery Complication-Case Presentation.
J Clin Med
December 2024
Department of Surgery IV, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540139 Targu Mures, Romania.
In recent decades, the advantages of minimizing surgical trauma have led to the development of minimally invasive surgical procedures. While the benefits often outweigh the risks, several challenges are encountered that are not present in conventional surgical approaches. Unilateral pulmonary edema (UPE) after mitral interventions performed through a right-sided approach is a rare but potentially life-threatening event.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!