The paradoxical role of inflammation in cardiac repair and regeneration.
Inflammation has emerged as a critical biological process contributing to nearly all aspects of cardiovascular diseases including heart failure. Heart failure represents the final consequence of a diverse set of initial insults to the myocardium, among which myocardial infarction (MI) is the most common cause. After MI, the lack of perfusion often leads to the death of cardiomyocytes. The necrotic cells trigger a cascade of inflammatory pathways that work to clear the dead cells and matrix debris, as well as to repair and heal damaged tissues. For the heart, an organ with limited regeneration capacity, the consequence of MI (termed post-MI remodeling) comprises a series of structural and functional changes, including scar formation at the infarct zone, reactive hypertrophy of the remaining cardiomyocytes at the noninfarct area, ventricular chamber dilatation, and molecular changes marked by fetal gene up-regulation, all of which have been linked to the activation of the inflammatory pathways. Inadequate or excessive inflammatory response may lead to improper cellular repair, tissue damage, and dysfunction. Herein, we summarize the current understanding of the role of inflammation in cardiac injury and repair and put forth the hypothesis that temporally regulated activation and suppression of inflammation may be critical for achieving effective cardiac repair and regeneration.
Jiang
Bingbing
B
Cardiac Muscle Research Laboratory, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB 431, Boston, MA 02115, USA. bjiang1@partners.org
Liao
Ronglih
R
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism*; D000074049:Cytokine TWEAK; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism; D015854:Up-Regulation
D015415:Biomarkers; D000074049:Cytokine TWEAK; D016207:Cytokines; D024243:HMGB1 Protein; D007375:Interleukin-1; D015850:Interleukin-6; C109743:TNFSF12 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors