Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells
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Morell Hita, MaríaFecha
2017Referencia bibliográfica
Delgado-Maroto V, Benitez R, Forte-Lago I, Morell M, Maganto-Garcia E, Souza-Moreira L, O'Valle F, Duran-Prado M, Lichtman AH, Gonzalez-Rey E, Delgado M. Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells. Sci Rep. 2017 Apr 13;7:46444. doi: 10.1038/srep46444. PMID: 28406244; PMCID: PMC5390288.
Patrocinador
This work was supported by Spanish Ministry of Economy and Competitiveness, Excellence Program from Junta de Andalucia and JAE-Predoc fellowship.Resumen
Atherosclerosis is a chronic inflammatory cardiovascular disease that is responsible of high mortality
worldwide. Evidence indicates that maladaptive autoimmune responses in the arterial wall play critical
roles in the process of atherosclerosis. Cortistatin is a neuropeptide expressed in the vascular system
and atherosclerotic plaques that regulates vascular calcification and neointimal formation, and inhibits
inflammation in different experimental models of autoimmune diseases. Its role in inflammatory
cardiovascular disorders is largely unexplored. The aim of this study is to investigate the potential
therapeutic effects of cortistatin in two well-established preclinical models of atherosclerosis, and
the molecular and cellular mechanisms involved. Systemic treatment with cortistatin reduced the
number and size of atherosclerotic plaques in carotid artery, heart, aortic arch and aorta in acute and
chronic atherosclerosis induced in apolipoprotein E-deficient mice fed a high-lipid diet. This effect was
exerted at multiple levels. Cortistatin reduced Th1/Th17-driven inflammatory responses and increased
regulatory T cells in atherosclerotic arteries and lymphoid organs. Moreover, cortistatin reduced the
capacity of endothelial cells to bind and recruit immune cells to the plaque and impaired the formation
of foam cells by enhancing cholesterol efflux from macrophages. Cortistatin emerges as a new
candidate for the treatment of the clinical manifestations of atherosclerosis