Laura M Pérez1,2, Beatriz de Lucas3, Aurora Bernal4,5, Beatriz G Gálvez3. 1. Universidad Europea de Madrid, Madrid, Spain. laura.mp.hospital@gmail.com. 2. FIB Hospital Infantil Universitario Niño Jesús, Madrid, Spain. laura.mp.hospital@gmail.com. 3. Universidad Europea de Madrid, Madrid, Spain. 4. FIB Hospital Infantil Universitario Niño Jesús, Madrid, Spain. 5. Stem Cell Aging and Cancer Research Group, Department of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
Abstract
BACKGROUND: The role of adipose tissue in the pathophysiology of cardiovascular disease remains a major subject of research. The objective of the present study was to dissect the molecular mechanisms that regulate the survival and differentiation of cardiac cells in an obese environment. MATERIAL AND METHODS: We isolated murine/human cardiac cells from adult hearts of control and obese mice/subjects and analyzed the communication between cardiac cells and adipocytes in vitro, as well as the effects on their main functions such as survival and differentiation. RESULTS: We found that the presence of visceral or subcutaneous adipocytes in the environment of cardiomyocytes or cardiac precursors provoked apoptosis or blocked differentiation, respectively, and these effects were mediated by secreted adipokines. Remarkably, cardiac precursors changed their fate and differentiated into mature adipocytes, contributing to the overall increase in adipose cell content. Inhibiting the adipokines TNF-α, visfatin, or HMGB1 could block the deleterious effects of adipokines on cardiac cells. CONCLUSIONS: Our findings demonstrate that mouse and human visceral adipose tissue contributes negatively to the homeostasis and regeneration of the heart. Moreover, our results suggest that blocking the action of certain adipokines might enhance cardiac differentiation and survival.
BACKGROUND: The role of adipose tissue in the pathophysiology of cardiovascular disease remains a major subject of research. The objective of the present study was to dissect the molecular mechanisms that regulate the survival and differentiation of cardiac cells in an obese environment. MATERIAL AND METHODS: We isolated murine/human cardiac cells from adult hearts of control and obesemice/subjects and analyzed the communication between cardiac cells and adipocytes in vitro, as well as the effects on their main functions such as survival and differentiation. RESULTS: We found that the presence of visceral or subcutaneous adipocytes in the environment of cardiomyocytes or cardiac precursors provoked apoptosis or blocked differentiation, respectively, and these effects were mediated by secreted adipokines. Remarkably, cardiac precursors changed their fate and differentiated into mature adipocytes, contributing to the overall increase in adipose cell content. Inhibiting the adipokines TNF-α, visfatin, or HMGB1 could block the deleterious effects of adipokines on cardiac cells. CONCLUSIONS: Our findings demonstrate that mouse and human visceral adipose tissue contributes negatively to the homeostasis and regeneration of the heart. Moreover, our results suggest that blocking the action of certain adipokines might enhance cardiac differentiation and survival.