L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex

Lamia Heikal; Anna Starr; Dania Hussein; Jesus Prieto-Lloret; Philip  Aaronson; Lea Ann Dailey; Manasi Nandi

doi:10.1016/j.jacbts.2018.01.015

L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex

Lamia Heikal, Anna Starr, Dania Hussein, Jesus Prieto-Lloret, Philip Aaronson, Lea Ann Dailey, Manasi Nandi

Institute of Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

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Abstract

Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH4. Here, the authors demonstrate that l-phenylalanine administration restores vascular function in a rodent model of hypertension, suggesting the GCH1-GFRP complex represents a rational therapeutic target for diseases underpinned by endothelial dysfunction.

Original language	English
Pages (from-to)	366-377
Journal	Journal of the American College of Cardiology
Volume	3
Issue number	3
Early online date	30 May 2018
DOIs	https://doi.org/10.1016/j.jacbts.2018.01.015
Publication status	E-pub ahead of print - 30 May 2018

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l-Phenylalanine Restores Vascular Function_HEIKAL_Accepted24January2018_GOLD VoR (CC BY)Final published version, 1.95 MBLicence: CC BY

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title = "L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex",

abstract = "Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH4. Here, the authors demonstrate that l-phenylalanine administration restores vascular function in a rodent model of hypertension, suggesting the GCH1-GFRP complex represents a rational therapeutic target for diseases underpinned by endothelial dysfunction.",

author = "Lamia Heikal and Anna Starr and Dania Hussein and Jesus Prieto-Lloret and Philip Aaronson and Dailey, {Lea Ann} and Manasi Nandi",

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T1 - L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex

AU - Heikal, Lamia

AU - Starr, Anna

AU - Hussein, Dania

AU - Prieto-Lloret, Jesus

AU - Aaronson, Philip

AU - Dailey, Lea Ann

AU - Nandi, Manasi

PY - 2018/5/30

Y1 - 2018/5/30

N2 - Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH4. Here, the authors demonstrate that l-phenylalanine administration restores vascular function in a rodent model of hypertension, suggesting the GCH1-GFRP complex represents a rational therapeutic target for diseases underpinned by endothelial dysfunction.

AB - Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH4. Here, the authors demonstrate that l-phenylalanine administration restores vascular function in a rodent model of hypertension, suggesting the GCH1-GFRP complex represents a rational therapeutic target for diseases underpinned by endothelial dysfunction.

U2 - 10.1016/j.jacbts.2018.01.015

DO - 10.1016/j.jacbts.2018.01.015

M3 - Article

SN - 0735-1097

VL - 3

SP - 366

EP - 377

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 3

ER -

L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex

Abstract

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