Heparan sulfate proteoglycans as regulators of vascular tone

• Grant number: 19/06653-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2019
• End date: March 20, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Simone Regina Potje
• Supervisor: Andreia Zago Chignalia
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Arizona, United States
• Associated to the scholarship: 16/21239-0 - Structure of caveolae and its modulation on glycocalyx and the mechanotransducer process in essential hypertension, BP.PD

Abstract

The glycocalyx is a known regulator of eNOS activity and thus, a regulator o NO production. We have made the novel discovery that knockout animals for glypican-1 and syndecan-1, components of the glycocalyx, have impaired endothelium-dependent vasodilation and vasocontriction. These effects are more significant in the glypican-1 knockout (Gpc-1-/-) when compared to the syndecan-1 knockout (Sdc-1-/-) and thus we hypothesize that glypican-1 (Gpc-1) is the main proteoglycan acting as a vascular tone modulator. Furthermore, the absence of Gpc-1 and Scd-1 alters calcium dynamics in vascular cells by unknown mechanisms. Herein, we seek to evaluate the relative contribution of Gpc-1 and Sdc-1 to the regulation of vascular tone and to dissect the mechanisms that result in changes of calcium dynamics in vascular cells with resulting impaired vasoconstriction. We will explore how impaired vasoconstriction may relate to the control of blood pressure in these knockout mice. Syndecan-1 knockout (Sdc-1-/-), glypican-1 knockout (Gpc-1-/-) and wild-type mice (CD1 will be used as control to Gpc-1-/- and C57BL6 will be used as control to Sdc-1-/-) will be used in this study. We will promote silencing of Gpc-1 in aortic rings of Sdc-1-/-, silence Sdc-1 in aortic rings of Gpc-1-/- and rescue the expression of Gpc-1 and Sdc-1 in aortic rings of the global knockouts. We will perform experiments of vascular reactivity and assess myogenic response. Furthermore, calcium fluorescence will be assessed in isolated cells and aortic rings by confocal and spinning disc microscopy.

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.; ISBATAN, AYMAN; TOSTES, RITA C.; BENDHACK, LUSIANE M.; DULL, RANDAL O.; CARVALHO-DE-SOUZA, JOAO L.; CHIGNALIA, ANDREIA Z.. Glypican 1 and syndecan 1 differently regulate noradrenergic hypertension development: Focus on IP3R and calcium. PHARMACOLOGICAL RESEARCH, v. 172, OCT 2021. (19/06653-2, 18/01853-0)

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., 2019-12-01. (18/01853-0, 19/06653-2, 16/21239-0)