P584PPARg and natriuretic peptides (NP) pathways are altered in adipose tissue from heart failure patients/ mesenchymal stromal cells (MMSC) as a tool to study cardiovascular metabolic disorders in vitro
Cardiovascular Research(2014)
Abstract
Background and aim: heart failure (HF) is associated with an increase of systemic and myocardial insulin resistance, decrease of metabolism of fatty acids (FA) and a shift toward glucose for ATP generation. The defects in FA oxidation, mitochondrial dysfunction and/or chronic activation of NP system are proposed as the possible triggers of development of metabolic disorder in HF; however the exact mechanisms of these disorders are largely unknown. Our goal was to investigate the alterations in PPAR and NP pathways in adipose tissue from heart failure patients using cellular in vitro models. Methods: in vitro adipodenic differentiation of previously characterized adipose (AD) and bone marrow (BM) derived MMSC from healthy donors (HD; n=4) and HF patients (n=4) was done. The stimulation of adipogenesis performed as widely described. Gene expression was measured by Q-PCR at days 0, 4, 8 and 11 after stimulation. Results: expression of genes responsible for energy metabolism, glucose utilization, and NP pathway during differentiation of MMSC from AD of HF and HD is demonstrated in Table 1. Dynamics of expression of these genes during differentiation of BMMSC were very similar. Conclusion: Our data indicate that in HF both, PPAR- and NP- dependent pathways as well as glucose utilization are altered in adipose of different origin. Results are in a good accordance with data from clinical and animal studies demonstrating that fetal gene program is reactivated in failing heart. We have proved here that adipose culture system from cardiovascular patients is a relatively easy available model to study mechanisms of cardiovascular metabolic disorders in vitro, and a good tool to test how adipose tissue responds at molecular levels to different physiological and pharmacological interventions. *p<0,05 vs control; *p<0,05 vs control; (**)p<0,05 vs HD *p<0,05 vs control; *p<0,05 vs control; (**)p<0,05 vs HD
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Key words
cardiovascular metabolic disorders,natriuretic peptides,adipose tissue,heart failure
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