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TNF-alpha participation in vascular dysfunction induced by chronic ethanol consumption: involvement of perivascular adipose tissue

Grant number: 14/09595-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2014
Effective date (End): February 05, 2017
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Carlos Renato Tirapelli
Grantee:Janaina Aparecida Simplicio
Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Chronic ethanol consumption acts as an important risk factor in the development of cardiovascular diseases, inducing increased blood pressure, impaired vascular reactivity, inflammation and increased oxidative stress in various tissues. In addition, studies shows that chronic ethanol consumption induces increased levels of TNF-alpha (tumor necrosis factor-alpha), a pro-inflammatory cytokine associated with vascular dysfunction. The TNFR1 receptor induces activation of intracellular pathways of MAPKs (Mitogen Activated Protein Kinases) and NFkB (nuclear factor kappa B) and causes reduced NO (nitric oxid) bioavailability and increased production of ROS (reactive oxygen species) and pro-inflammatory cytokines. In addition, vascular inflammation caused by ethanol consumption may involve the participation of PVAT (perivascular adipose tissue), known as a major source of adipokines and pro-inflammatory cytokines, including TNF-alpha. Under physiological conditions, PVAT plays a beneficial action in the regulation of vascular tone, but can be harmful in pathological situations. Given these data, the hypothesis of this study is that chronic ethanol consumption stimulates the production of TNF-±, which induces an increase in ROS, reduction of NO, activation of MAPKs and NFkB, interleukins production (IL-1B, IL-6 and IL-18). There will be loss in the protective role of PVAT on vascular tone. Such processes lead to vascular dysfunction causing altered vascular reactivity and increased blood pressure. Therefore, this study is designed to assess the involvement of TNF-alpha on vascular effects induced by chronic ethanol consumption and the involvement of PVAT in this process. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SIMPLICIO, JANAINA A.; GONZAGA, NATALIA A.; NAKASHIMA, MARCELO A.; DE MARTINIS, BRUNO S.; CUNHA, THIAGO M.; TIRAPELLI, LUIS F.; TIRAPELLI, CARLOS R.. Tumor necrosis factor-alpha receptor 1 contributes to ethanol-induced vascular reactive oxygen species generation and hypertension. JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION, v. 11, n. 10, p. 684-696, . (14/09595-0)
NAKASHIMA, MARCELO A.; SILVA, CARLA B. P.; GONZAGA, NATALIA A.; SIMPLICIO, JANAINA A.; OMOTO, ANA C. M.; TIRAPELLI, LUIS F.; TANUS-SANTOS, JOSE E.; TIRAPELLI, CARLOS R.. Chronic ethanol consumption increases reactive oxygen species generation and the synthesis of pro-inflammatory proteins in the heart through TNFR1-dependent mechanisms. CYTOKINE, v. 121, . (14/09595-0, 16/11883-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SIMPLICIO, Janaina Aparecida. Role of TNF-a in vascular dysfunctions induced by chronic ethanol consumption: involvement of perivascular adipose tissue. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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