Inhibition of CD34+ cell migration by matrix metalloproteinase-2 during acute myocardial ischemia, counteracted by ischemic preconditioning
| Autor: | Dominika Lukovic, Andreas Spannbauer, Stefan P. Kastl, Noemi Pavo, Katrin Zlabinger, Ljubica Mandic, Inna Sabdyusheva Litschauer, Denise T. Weidenauer, Anikó Pósa, Christoph Kaun, Alfred Gugerell, Johannes Winkler, Mariann Gyöngyösi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine acute myocardial infarction 030204 cardiovascular system & hematology Pharmacology Matrix metalloproteinase CXCR4 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine preconditioning medicine Myocardial infarction General Pharmacology Toxicology and Pharmaceutics Immune Response Heart Failure General Immunology and Microbiology biology business.industry Cell migration General Medicine Articles Hypoxia (medical) medicine.disease stem cell mobilization 030104 developmental biology medicine.anatomical_structure biology.protein Ischemic preconditioning medicine.symptom business MMP-2 Neuroscience SDF-1/CXCR4 axis Artery Research Article |
| Zdroj: | F1000Research |
| ISSN: | 2046-1402 |
| Popis: | Background. Mobilization of bone marrow-origin CD34+ cells was investigated 3 days (3d) after acute myocardial infarction (AMI) with/without ischemic preconditioning (IP) in relation to stromal-derived factor-1 (SDF-1α)/ chemokine receptor type 4 (CXCR4) axis, to search for possible mechanisms behind insufficient cardiac repair in the first days post-AMI. Methods. Closed-chest reperfused AMI was performed by percutaneous balloon occlusion of the mid-left anterior descending (LAD) coronary artery for 90min, followed by reperfusion in pigs. Animals were randomized to receive either IP initiated by 3x5min cycles of re-occlusion/re-flow prior to AMI (n=6) or control AMI (n=12). Blood samples were collected at baseline, 3d post-AMI, and at 1-month follow-up to analyse chemokines and mobilized CD34+ cells. To investigate the effect of acute hypoxia, SDF-1α and matrix metalloproteinase (MMP)-2 in vitro were assessed, and a migration assay of CD34+ cells toward cardiomyocytes was performed. Results. Reperfused AMI induced significant mobilisation of CD34+ cells (baseline: 260±75 vs. 3d: 668±180; PIn vitro, CD34+ cell migration toward cardiomyocytes was enhanced by SDF-1α, which was completely abolished by 90min hypoxia and co-incubation with MMP-2. Conclusions. Non-conditioned AMI induces MMP-2 release, hampering the ischemia-induced increase in SDF-1α and CXCR4 by cleaving the SDF-1α/CXCR4 axis, with diminished mobilization of the angiogenic CD34+ cells. IP might influence CD34+ cell mobilization via inhibition of MMP-2. |
| Databáze: | OpenAIRE |
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