Surfaceome remodeling in advanced heart failure
Heart Failure (HF) is a condition where the heart cannot pump enough blood to meet the body’s demands and is a leading cause of morbidity and mortality in the US. Despite advances in medical therapy, ~10% of the nearly 6 million HF patients fail to respond to treatment and progress to develop advanced heart failure (AHF). Progression to AHF is tightly linked to pathologic cardiac remodeling, characterized by hypertrophy and/or loss of cardiomyocytes, pathological cardiac fibroblast activation, cardiac fibrosis, and adverse extracellular matrix remodeling resulting in diminished ventricular function.
Drug development for AHF has had limited success over the past decade. Going forward, we expect efforts to develop therapeutic targets for heart failure will shift away from secondary effects (e.g., neurohormonal activation, renal function) and towards combating the development and progression of structural cardiac abnormalities associated with heart failure. Consequently, analysis of the surfaceome will be critical to advances in the cardiovascular field given its critical role in structural integrity, cell communication (direct, electrical, hormonal), immunity and cell protection.
Our laboratory has developed innovative approaches to study primary human heart cells. These include isolation of primary cardiomyocytes and cardiac fibroblasts suitable for proteomic and glycomic analysis and development of new microscale technologies that enable discovery of cell surface proteins and glycan structures from small numbers of human primary cells. These efforts have resulted in the discovery of cardiomyocyte cell surface proteins that differ among failing and non-failing hearts - a resource of potential therapeutic targets, biomarkers, and new insights into molecular mechanisms of disease.
Mahr & Gundry, Hold or fold--proteins in advanced heart failure and myocardial recovery, Proteomics Clinical Applications, 2015.