Abstract 18563: Sigmar1 Protects the Heart Against Ischemia/Reperfusion Injury
Introduction: Accumulative evidence indicates that increased expression and presumably activity of molecular chaperones are protective against cardiac hypertrophic remodling and ischemia/reperfusion (I/R) injury-induced heart failure. Sigma-1 receptor (Sigmar1) is a highly expressed molecular chaperone protein in the heart. However, Sigmar1’s molecular functions and involvement in disease processes in the heart remains obscure.
Hypothesis: We investigated the functional role of Sigmar1 in cardiac I/R injury induced pathological remodeling and heart failure in mouse heart.
Methods and Results: Sigmar1 is a chaperone protein expressing in normal heart and temporal changes following I/R-injury showed increased level of Sigmar1 protein expression. To define the structural, functional and physiological significance of Sigmar1 in cardiac stress response, we subjected the cardiac specific Sigmar1 transgenic mice and Sigmar1 knockout mice to I/R-injury. We generated the transgenic mice with cardiac-specific overexpression of Sigmar1 and they exhibited normal morphometry, ultrastructure, hemodynamics and contractile function. Sigmar1 Tg mouse hearts showed significantly reduced infarct size 24 hours after reperfusion. These mice also showed protection from chronic I/R-injury induced adverse cardiac remodeling and improved cardiac function even 12 weeks after reperfusion injury. In contrast, Sigmar1 knockout mice showed normal morphometry but exhibited significantly altered cardiac hemodynamics and ultrastructure at base line. Sigmar1 knockout mice showed increased infarct size, were susceptible to adverse cardiac remodeling and exhibited aggravated cardiac dysfunction following I/R-injury.
Conclusions: Sigmar1 is a novel chaperone protein in the heart and protects I/R-injury induced adverse cardiac remodeling and dysfunction.
Author Disclosures: S. Alam: None. A. Chowdhury: None. A. Orr: None. J. James: None. H. Osinska: None. J. Molkentin: None. B. Blaxall: None. J. Robbins: None. J. Lorenz: None. M. Bhuiyan: None.
- © 2016 by American Heart Association, Inc.