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Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction.

ABSTRACT: Mesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and local inflammation both dynamically and rapidly change after MI. Whether and how inflammatory cytokines could couple with stiffness change to affect MSC engraftment in the infarct zone still remain unclear. In this study, we characterized dynamic stiffness changes of and inflammatory cytokine expression in the infarct region of rat heart within a month after MI. We found that the tissue stiffness of the heart tissue gradually increased and peaked 21 days after MI along with the rapid upregulation of tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), and interleukin-1? (IL-1?) in the first 3 days, followed by a sharp decline. We further demonstrated in vitro that immobilized inflammatory cytokine IL-6 performed better than the soluble form in enhancing MSC adhesion to stiffened substrate through IL-6/src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP2)/integrin signaling axis. We also confirmed such mechano-immune coupling of tissue stiffness and inflammatory cytokines in modulating MSC engraftment in the rat heart after MI in vivo. Our study provides new mechanistic insights of mechanical-inflammation coupling to improve MSC mechanosensing and adhesion, potentially benefiting MSC engraftment and its clinical therapy for MI.

SUBMITTER: Zhu D

PROVIDER: S-EPMC7645114 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction.

Zhu Dan D Wu Peng P Xiao Changchen C Hu Wei W Zhang Tongtong T Hu Xinyang X Chen Wei W Wang Jian'an J

Frontiers in cell and developmental biology 20201023

Mesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and local inflammation both dynamically and rapidly change after MI. Whether and how inflammatory cytokines could couple with stiffness change to affect MSC engraftment in the infarct zone still remain unclea ...[more]

PMID: 33195229

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Project description:There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight-6:00 A.M., 6:00 A.M.-noon, noon-6:00 P.M. and 6:00 P.M.-midnight. We used peak creatine kinase as a surrogate marker of infarct size.Midnight-6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight-6:00 A.M. patients and lowest among 6:00 A.M.-noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight-6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.-noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).We observed a circadian peak and nadir in infarct size during STEMI onset from midnight-6:00A.M and 6:00A.M.-noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.

Dataset Information

Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction.

Publications

Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction.

Similar Datasets

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