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

• Grant number: 17/14797-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2018
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Lusiane Maria Bendhack
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Cristina Antoniali Silva

Abstract

The endothelial glycocalyx is formed primarily by proteoglycans, glycoproteins and glycosaminoglycans (GAGs) and it 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 nitric oxide (NO) production. Essential hypertension is a multifactorial disorder that is associated with reduced NO bioavailability. Spontaneously hypertensive rats (SHR) have genetic predisposition to the development of essential hypertension without specific etiology. It is 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 as compared to normotensive rat arteries. It is also known that the number of caveolae is lower in the SHR than in normotensive rat vessels. Additionally, changes occur on proteoglycans in resistance vessels of SHR, which suggest 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)

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)

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, APR 30 2019. (17/14797-9, 16/22180-9, 16/21239-0)