Can heart function lost to disease be regenerated by therapeutic targeting of cardiac scar tissue?. (October 2016)

• Record Type: Journal Article
• Authors: Ongstad, Emily L.; Gourdie, Robert G.
• Is Part Of: Seminars in cell & developmental biology. Volume 58(2016)
• Page Start: 41
• Page End: 54
• Publication Date: 2016-10
• Subjects: αCT1 alpha-carboxyl-terminal peptide 1 -- AP action potential -- APD action potential duration -- BMCs bone marrow derived cells -- CV conduction velocity -- Cx43 connexin 43 -- ECM extracellular matrix -- GJ gap junction -- GJIC gap junction intercellular communication -- IBZ injury border zone -- ID intercalated disc -- Kir2.1 inward rectifying potassium current 2.1 -- KCNH2 voltage gated potassium channel -- Kv1.3 voltage gated potassium channel 1.3 -- LV left ventricular -- MI myocardial infarction -- miR-1 microRNA-1 -- MMP matrix metalloproteinase -- SERCA sarcoplasmic reticulum calcium ATPase -- SCN4a voltage gated sodium channel isoform 4a -- SCN5a voltage gated sodium channel isoform 5a -- SR sarcoplasmic reticulum -- TIMP tissue inhibitor of metalloproteinase -- TGF-β transforming growth factor-β; Myocardial infarction -- Regeneration -- Fibrosis -- Structure -- Tissue properties; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2016.05.020
• Languages: English
• ISSNs: 1084-9521

Abstract

Highlights: The adult heart cannot regenerate, so myocardial infarction (MI) results in a scar. Significant electrical and mechanical remodeling occurs after MI, resulting in arrhythmias. Modifying scar properties is a viable strategy for improving post-MI prognosis. Proteins involved in conduction and fibrous tissue structure are primary targets for altering scar properties. Further study is required to understand how modifying scar tissue affects heart function. Abstract: Myocardial infarction results in scar tissue that cannot actively contribute to heart mechanical function and frequently causes lethal arrhythmias. The healing response after infarction involves inflammation, biochemical signaling, changes in cellular phenotype, activity, and organization, and alterations in electrical conduction due to variations in cell and tissue geometry and alterations in protein expression, organization, and function – particularly in membrane channels. The intensive research focus on regeneration of myocardial tissues has, as of yet, only met with modest success, with no near-term prospect of improving standard-of-care for patients with heart disease. An alternative concept for novel therapeutic approach is the rejuvenation of cardiac electrical and mechanical properties through the modification of scar tissue. Several peptide therapeutics, locally applied genetic therapies, or delivery of genetically modified cells have shown promise in improving the characteristics of the fibrous scar and post-myocardial infarction prognosis in experimental models. This review highlights several factors that contribute to arrhythmogenesis in scar formation and how these might be targeted to regenerate some of the electrical and mechanical function of the post-MI scar.