FoxO4 controls sGCβ transcription in vascular smooth muscle

Author:

Galley Joseph C.12ORCID,Miller Megan P.1,Sanker Subramaniam2ORCID,Liu Mingjun13,Sharina Iraida4,Martin Emil4,Gomez Delphine15,Straub Adam C.126ORCID

Affiliation:

1. Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania

2. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania

3. Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania

4. Department of Cardiovascular Medicine, University of Texas Health Science Center, Houston, Texas

5. Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

6. Center for Microvascular Research, University of Pittsburgh, Pittsburgh, Pennsylvania

Abstract

One of the key mechanisms of vascular smooth muscle cell (SMC) dilation occurs through nitric oxide (NO)-dependent induction of soluble guanylyl cyclase (sGC) by means of its β-subunit. Herein, we are the first to identify Forkhead box subclass O protein 4 (FoxO4) as a key transcriptional regulator of GUCY1B3 expression, which codes for sGCβ protein in human and animal SMCs. This discovery will likely have important implications for the future usage of antihypertensive and vasodilatory therapies which target NO production, sGC, or FoxO transcription factors.

Funder

American Heart Association

HHS | NIH | National Institute of General Medical Sciences

HHS | NIH | National Heart, Lung, and Blood Institute

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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