Transcriptional changes in bone marrow stromal cells of patients with heart failure

Abstract

It is proposed that patients with heart failure may have not only myocardial dysfunction, but also a reduced regenerative capacity of stem cells. However, very little is known about bone marrow stromal cell (BMSC) characteristics in heart failure and its comorbidities (obesity and/or diabetes). We hypothesized that metabolic alterations associated with the latter will be reflected in altered expression of key genes related to angiogenesis, inflammation, and tissue remodeling in patient-derived BMSCs. We found that BMSCs of heart failure patients with lower body mass index have enhanced expression of genes involved in extracellular matrix remodeling. In particular, body mass index <30 was associated with upregulated expression of genes encoding collagen type I, proteases and protease activators (MMP2, MMP14, uPA), and regulatory molecules (CTGF, ITGβ5, SMAD7, SNAIL1). In contrast, these transcript levels did not differ significantly between BMSCs from obese heart failure patients and healthy subjects. Comorbidities (including obesity and diabetes) are known to play role in heart failure progression rate and outcome of the disease. We thus suggest that key molecular targets identified in this study should become the target of the subsequent focused studies. In the future, these targets may find some use in the clinical setting.

Keywords: :

• bone marrow stromal cells
• gene expression
• heart failure
• body mass index
• extracellular matrix remodeling

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Anna Bilibina and Olga Tarasova for isolation of human BMSCs, Dr Dmitry Motorin for collecting bone marrow samples, Dr Martine Jandrot-Perrus for valuable advice, and Dr Anna Kostareva for general support. This work was supported by the Ministry of Education and Science of the Russian Federation (state contract 02.527.11.0007), by the European Commission under the 7th Framework Programme (grant agreement 241558, SICA-HF), and by the Ministry of Health of the Russian Federation under the program of the Union State “Development of New Methods and Technologies for Regenerative Therapy of Abnormal Tissues and Organs Using Stem Cells” (state contract К-32-NIR/111-3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.