Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation.

Federica Limana, Antonia Germani, Antonella Zacheo, Jan Kajstura, Anna Di Carlo, Giovanna Borsellino, Omar Leoni, Roberta Palumbo, Luca Battistini, Raffaella Rastaldo, Susanne Müller, Giulio Pompilio, Piero Anversa, Marco E. Bianchi, Maurizio C. Capogrossi

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

High-mobility group box 1 protein (HMGB1) is a chromatin protein that is released by inflammatory and necrotic cells. Extracellular HMGB1 signals tissue damage, stimulates the secretion of proinflammatory cytokines and chemokines, and modulates stem cell function. The present study examined exogenous HMGB1 effect on mouse left-ventricular function and myocyte regeneration after infarction. Myocardial infarction was induced in C57BL/6 mice by permanent coronary artery ligation. After 4 hours animals were reoperated and 200 ng of purified HMGB1 was administered in the peri-infarcted left ventricle. This intervention resulted in the formation of new myocytes within the infarcted portion of the wall. The regenerative process involved the proliferation and differentiation of endogenous cardiac c-kit+ progenitor cells. Circulating c-kit+ cells did not significantly contribute to HMGB1-mediated cardiac regeneration. Echocardiographic and hemodynamic parameters at 1, 2, and 4 weeks demonstrated a significant recovery of cardiac performance in HMGB1-treated mice. These effects were not observed in infarcted hearts treated either with the unrelated protein glutathione S-transferase or a truncated form of HMGB1. Thus, HMGB1 appears to be a potent inducer of myocardial regeneration following myocardial infarction.

Original languageEnglish
Title of host publicationCirculation research.
Volume97
Edition8
Publication statusPublished - Oct 14 2005

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation.'. Together they form a unique fingerprint.

  • Cite this

    Limana, F., Germani, A., Zacheo, A., Kajstura, J., Di Carlo, A., Borsellino, G., Leoni, O., Palumbo, R., Battistini, L., Rastaldo, R., Müller, S., Pompilio, G., Anversa, P., Bianchi, M. E., & Capogrossi, M. C. (2005). Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation. In Circulation research. (8 ed., Vol. 97)