Differential protein expression and basal lamina remodeling in human heart failure. Issue 5 (25th January 2016)

• Record Type: Journal Article
• Authors: Kim, Evelyn H.; Galchev, Vladimir I.; Kim, Jin Young; Misek, Sean A.; Stevenson, Tamara K.; Campbell, Matthew D.; Pagani, Francis D.; Day, Sharlene M.; Johnson, T. Craig; Washburn, Joseph G.; Vikstrom, Karen L.; Michele, Daniel E.; Misek, David E.; Westfall, Margaret V.
• Is Part Of: Proteomics. Volume 10:Issue 5(2016)
• Page Start: 585
• Page End: 596
• Publication Date: 2016-01-25
• Subjects: Basal lamina -- Heart failure -- Myocardium -- Proteins -- Remodeling; Proteomics -- Periodicals; 572.605
• DOI: 10.1002/prca.201500099
• Languages: English
• ISSNs: 1862-8346

Abstract

Abstract : Purpose: A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing protein expression in ischemic failing (F) and nonfailing (NF) human hearts. Experimental design: Protein expression differences were investigated using multidimensional protein identification and validated by Western analysis. This approach detected basal lamina (BL) remodeling, and further studies analyzed samples for evidence of structural BL remodeling. A rat model of pressure overload (PO) was studied to determine whether nonischemic stressors also produce BL remodeling and impact cellular adhesion. Results: Differential protein expression of collagen IV, laminin α2, and nidogen‐1 indicated BL remodeling develops in F versus NF hearts Periodic disruption of cardiac myocyte BL accompanied this process in F, but not NF heart. The rat PO myocardium also developed BL remodeling and compromised myocyte adhesion compared to sham controls. Conclusions and clinical relevance: Differential protein expression and evidence of structural and functional BL alterations develop during heart failure. The compromised adhesion associated with this remodeling indicates a high potential for dysfunctional cellular integrity and tethering in failing myocytes. Therapeutically targeting BL remodeling could slow or prevent the progression of heart disease.