Obesity is associated with dysfunction of the white adipose tissue, with an increased release of pro-inflammatory cytokines. This condition is also associated with insulin resistance and endothelial dysfunction. The mechanisms by which cytokines released by the adipose tissue interfere with vascular function or with the modulation of vascular function in obesity are not yet fully understood. Moreover, the effects of the cytokine / adipokine chemerin on vascular function are unknown. To our knowledge there is no study in the literature addressing the effects of chemerin on vascular reactivity. Thus, in this project we intend to investigate not only the effects of this cytokine in vascular reactivity, but also understand the mechanisms by which this cytokine modifies vascular function. Based on preliminary data, we formulated the following working hypothesis: chemerin increases vascular reactivity to constrictor stimuli via activation of MAPKs (mitogen-activated protein kinases) and RhoA / Rho kinase signaling pathways. Our specific objectives are to determine: 1) if chemerin promotes changes in vascular reactivity; 2) whether the changes in vascular reactivity promoted by chemerin are mediated by changes in the function of endothelial cells or vascular smooth muscle cells; 3) what signaling pathways (focusing on the MAPKs and RhoA / Rho kinase pathways) are being modified by chemerin and how they contribute to changes in vascular reactivity produced by this cytokine; 4) if chemerin alters vascular sensitivity to insulin. Our studies contribute to a better understanding of the role of factors released by the visceral adipose tissue on vascular function and thus on the vascular lesions in obesity and diseases associated with obesity, such as type 2 diabetes, hypertension and cardiovascular diseases.
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