ABSTRACT
BACKGROUND AND AIMS: Obesity promotes a persistent inflammatory process in the adipose tissue, activating the endothelium and leading to vascular dysfunction. Preadipocytes can interact with endothelial cells in a paracrine way stimulating angiogenesis. However, the potential of preadipocytes from adipose tissue of high fat diet (HFD) fed animal to stimulate angiogenesis has not been evaluated yet. The aim of this study was to investigate the effects of such diet on the angiogenic potential of preadipocytes in a mice model. METHODS AND RESULTS: We have evaluated body weight gain, fasting glucose levels and insulin resistance, mRNA expression in preadipocytes and endothelial cells after co-culture with preadipocytes, in vivo vascular function and in vitro endothelial cell migration and tubulogenesis. High fat diet promoted an increase in body weight, glycemic index and insulin resistance in mice. Preadipocytes mRNA expression of factors involved in angiogenesis was higher in these animals. In endothelial tEnd cells mRNA expression of factors involved in vessel growth were higher after co-culture with preadipocytes derived from mice fed with HFD. Although no significant differences were observed in in vivo vasodilatation response between control and HFD groups, endothelial tEnd cells showed an increase in migration and tubulogenesis when cultivated with conditioned media from preadipocytes derived from mice fed with HFD. CONCLUSION: Hypoxic and growth factors produced by preadipocytes derived from mice fed with HFD have higher capacity than preadipocytes derived from mice fed with standard diet to stimulate the angiogenic potential of endothelial cells, contributing to vascular disorders in obesity.
Subject(s)
Adipocytes/metabolism , Angiogenic Proteins/metabolism , Diet, High-Fat , Endothelial Cells/metabolism , Neovascularization, Physiologic , Obesity/metabolism , Paracrine Communication , Angiogenic Proteins/genetics , Animals , Cell Adhesion , Cell Line , Cell Movement , Cell Proliferation , Coculture Techniques , Culture Media, Conditioned/metabolism , Disease Models, Animal , Male , Mice, Inbred C57BL , Obesity/genetics , Obesity/physiopathology , Signal Transduction , VasodilationABSTRACT
Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.
Subject(s)
Lung/physiology , Mechanoreceptors/physiology , Mechanotransduction, Cellular/physiology , Extracellular Matrix/physiology , Humans , Intercellular Junctions/physiology , Intracellular Membranes/physiology , Lung/cytology , Stress, MechanicalABSTRACT
Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.
