Role of CETP expression in the macrophage redox state: possible consequences to inflammation and atherosclerosis

• Grant number: 17/02903-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: June 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Aníbal Eugênio Vercesi
• Grantee: Gabriel de Gabriel Taffarello Dorighello
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases, AP.TEM
• Associated scholarship(s): 20/14176-7 - Identifying the regulatory functions of nuclear lipid synthesis and storage pathways, BE.EP.PD 19/26521-3 - Identifying the regulatory functions of nuclear lipid synthesis and storage pathways, BE.EP.PD

Abstract

Cardiovascular diseases remained as major cause of mortality worldwide due to atherosclerosis. The CETP is a glycoprotein, which promote the lipid transfer between plasma apolipoprotein B lipoprotein to HDL. Although CETP activity leads to decreases in HDL-cholesterol plasma levels, clinical tests using CETP inhibitors showed no benefits or increased mortality. Experimental evidence suggests that CETP also present anti-oxidant, anti-inflammatory and anti-adipogenic functions. Human CETP transgenic mice showed lower mortality rates and reduced inflammation in response to LPS toxin. In addition, a positive correlation between CETP plasma levels and survival rates of patient with sepsis was described. Regarding atherogenesis, the local oxidative stress is consider the earliest event and it is tightly associated with inflammation. The mitochondria is a relevant source of reactive oxygen species (ROS) in cells from several tissue. In LPS activated macrophages, the mitochondrial ROS generation precedes the pro-inflammatory cytokines secretion, and these cytokines contribute to vicious cycle ROS-inflammation-ROS. Considering that CETP is anti-inflammatory in acute phase situations, our hypothesis is that the CETP expression could reduce the mitochondrial ROS production and, in this way, would reduce also the inflammation signaling induced by mitochondrial ROS. Therefore, the objective of this project is to investigate whether CETP affects the mitochondrial ROS production in macrophages in the context of atherogenesis.

Scientific publications

(6)

(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)

ASSIS, LEANDRO HENRIQUE DE PAULA; DORIGHELLO, GABRIEL DE GABRIEL; RENTZ, THIAGO; SOUZA, JANE CRISTINA DE; VERCESI, ANIBAL EUGENIO; DE OLIVEIRA, HELENA COUTINHO FRANCO. In Vivo Pravastatin Treatment Reverses Hypercholesterolemia Induced Mitochondria-Associated Membranes Contact Sites, Foam Cell Formation, and Phagocytosis in Macrophages. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 9, p. 17-pg., 2022-03-15. (17/03402-3, 17/17728-8, 17/02903-9, 13/50615-1)

SALERNO, ALESSANDRO G.; RENTZ, THIAGO; DORIGHELLO, GABRIEL G.; MARQUES, ANA CAROLINA; LORZA-GIL, ESTELA; WANSCHEL, AMARYLIS C. B. A.; DE MORAES, AUDREY; VERCESI, ANIBAL E.; OLIVEIRA, HELENA C. F.. Lack of mitochondrial NADP(H)-transhydrogenase expression in macrophages exacerbates atherosclerosis in hypercholesterolemic mice. Biochemical Journal, v. 476, p. 21-pg., 2019-12-01. (11/15103-4, 11/15101-1, 13/05497-0, 11/50400-0, 17/02903-9, 13/07607-8, 17/17728-8)

SALERNO, ALESSANDRO G.; RENTZ, THIAGO; DORIGHELLO, GABRIEL G.; MARQUES, ANA CAROLINA; LORZA-GIL, ESTELA; WANSCHEL, AMARYLIS C. B. A.; DE MORAES, AUDREY; VERCESI, ANIBAL E.; OLIVEIRA, HELENA C. F.. Lack of mitochondrial NADP(H)-transhydrogenase expression in macrophages exacerbates atherosclerosis in hypercholesterolemic mice. Biochemical Journal, v. 476, n. 24, p. 3769-3789, DEC 2019. (11/15101-1, 11/15103-4, 11/50400-0, 13/05497-0, 17/17728-8, 13/07607-8, 17/02903-9)

ASSIS, LEANDRO HENRIQUE DE PAULA; DORIGHELLO, GABRIEL DE GABRIEL; DE OLIVEIRA, HELENA COUTINHO FRANCO. Pro-inflammatory polarization of macrophages is associated with reduced endoplasmic reticulum-mitochondria interaction. Biochemical and Biophysical Research Communications, v. 606, p. 7-pg., 2022-05-28. (13/50615-1, 17/17728-8, 17/02903-9, 17/03402-3)

DORIGHELLO, GABRIEL G.; ASSIS, LEANDRO H. P.; RENTZ, THIAGO; MORARI, JOSEANE; SANTANA, MONIQUE F. M.; PASSARELLI, MARISA; RIDGWAY, NEALE D.; VERCESI, ANIBAL E.; OLIVEIRA, HELENA C. F.. Novel Role of CETP in Macrophages: Reduction of Mitochondrial Oxidants Production and Modulation of Cell Immune-Metabolic Profile. ANTIOXIDANTS, v. 11, n. 9, p. 17-pg., 2022-09-01. (13/07607-8, 17/17728-8, 17/02903-9, 19/18431-4, 21/02401-9, 17/03402-3)

DORIGHELLO, GABRIEL G.; ROVANI, JULIANA C.; PAIM, BRUNO A.; RENTZ, THIAGO; ASSIS, LEANDRO H. P.; VERCESI, ANIBAL E.; OLIVEIRA, HELENA C. F.. Mild Mitochondrial Uncoupling Decreases Experimental Atherosclerosis, A Proof of Concept. JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, v. 29, n. 6, p. 14-pg., 2022-01-01. (17/17728-8, 13/07607-8, 17/02903-9, 14/02819-0, 17/03402-3)