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Structure of caveolae and its modulation on glycocalyx and the mechanotransducer process in essential hypertension

Grant number: 16/21239-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): April 01, 2017
Effective date (End): April 30, 2021
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Rita de Cassia Aleixo Tostes Passaglia
Grantee:Simone Regina Potje
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):19/06653-2 - Heparan sulfate proteoglycans as regulators of vascular tone, BE.EP.PD   18/01853-0 - The mechanotransduction pathways activated by increased intravascular pressure in glypican-1 and syndecan-1 knockout mice, BE.EP.PD


The endothelial glycocalyx is formed primarily of proteoglycans, glycoproteins and glycosaminoglycans (GAGs) and has been described as a structure responsible for mechanotransduction which is a translation of the biomechanical forces in biochemical signaling in endothelial cells, promoting activation of endothelial nitric oxide synthase (eNOS) and production nitric oxide (NO). Essential hypertension is a disorder of multifactorial origin, which affects 20% of adults in industrialized countries and is associated with reduced bioavailability of NO. Spontaneously hypertensive rats (SHR) has genetic predisposition to the development of essential hypertension without specific etiology becomeing an excellent model for the study of essential hypertension. In SHR, the expression of eNOS is reduced in conductance vessels. However, there is no change in eNOS expression in resistance arteries, but eNOS activity is reduced when compared to normotensive rats. It is also known that the number of caveolae is diminished in the SHR compared with normotensive rats. Additionally, changes occur on proteoglycans in resistance vessels of SHR, which suggests that proteoglycans contribute to the increased peripheral vascular resistance in hypertensive states. Therefore, the hypothesis of our work is that essential hypertension causes changes in glycocalyx composition leading to impairment of caveolae structure. This leads to the loss in the mechanotransduction process and consequently to lower activity of eNOS and reduced NO production in resistance vessels of SHR, contributing to essential hypertension. (AU)

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Scientific publications (5)
(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)
POTJE, SIMONE R.; GRANDO, MARCELLA D.; CHIGNALIA, ANDREIA Z.; ANTONIALI, CRISTINA; BENDHACK, LUSIANE M.. Reduced caveolae density in arteries of SHR contributes to endothelial dysfunction and ROS production. SCIENTIFIC REPORTS, v. 9, . (17/14797-9, 16/22180-9, 16/21239-0)
POTJE, SIMONE R.; COSTA, TIAGO J.; FRAGA-SILVA, THAIS F. C.; MARTINS, RONALDO B.; BENATTI, MAIRA N.; ALMADO, CARLOS E. L.; DE SA, KEYLA S. G.; BONATO, VANIA L. D.; ARRUDA, EURICO; LOUZADA-JUNIOR, PAULO; et al. Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients. Life Sciences, v. 276, . (17/25116-2, 16/21239-0, 13/08216-2, 20/05270-0)
POTJE, SIMONE R.; BENDHACK, LUSIANE MARIA; TOSTES, RITA DE CASSIA; DULL, RANDAL; CARVALHO-DE-SOUZA, JOAO; CHIGNALIA, ANDREIA. Heparan Sulfate Proteoglycans Modulate Calcium Storage and Mobility in Aortic Rings. Free Radical Biology and Medicine, v. 145, p. 1-pg., . (18/01853-0, 19/06653-2, 16/21239-0)
POTJE, SIMONE R.; GRANDO, MARCELLA D.; CHIGNALIA, ANDREIA; ANTONIALI, CRISTINA; BENDHACK, LUSIANE MARIA. Disrupting caveolae promotes eNOS uncoupling and ROS production. Free Radical Biology and Medicine, v. 128, p. 2-pg., . (16/21239-0)
COSTA, TIAGO J.; POTJE, SIMONE R.; FRAGA-SILVA, THAIS F. C.; DA SILVA-NETO, JULIO A.; BARROS, PAULA R.; RODRIGUES, DANIEL; MACHADO, MIRELE R.; MARTINS, RONALDO B.; SANTOS-EICHLER, ROSANGELA A.; BENATTI, MAIRA N.; et al. itochondrial DNA and TLR9 activation contribute to SARS-CoV-2-induced endothelial cell damag. VASCULAR PHARMACOLOGY, v. 142, . (13/08216-2, 16/21239-0, 17/25116-2)

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