title: 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.
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Izida R
authors.initials: IR
authors.lastname: Minullina
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation; Permanent affiliation: Saint Petersburg State University; St. Petersburg, Russian Federation.
authors.forename: Nina P
authors.initials: NP
authors.lastname: Alexeyeva
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Anisimov
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Puzanov
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Kozlova
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Yurii V
authors.initials: YV
authors.lastname: Sviryaev
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Andrey Yu
authors.initials: AY
authors.lastname: Zaritskey
authors.affiliation: Federal Almazov Medical Research Centre; St. Petersburg, Russian Federation.
authors.forename: Eugeniy V
authors.initials: EV
authors.lastname: Shlyakhto
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D061251:Primary Cell Culture; D014158:Transcription, Genetic
keywords: body mass index; bone marrow stromal cells; extracellular matrix remodeling; gene expression; heart failure