Blood pressure homeostasis is maintained by a P311-TGF-beta axis Journal Article

Local Library Link: Find It @ Loyola

Authors: Badri, K. R.; Yue, M.; Carretero, O. A.; Aramgam, S. L.; Cao, J.; Sharkady, S.; Kim, G. H.; Taylor, G. A.; Byron, K. L.; Schuger, L.
Article Title: Blood pressure homeostasis is maintained by a P311-TGF-beta axis
Abstract: P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311-/-) mice display learning and memory defects, but alterations in their vasculature have not been previously described. Here we report that P311-/- mice are markedly hypotensive with accompanying defects in vascular tone and VSMC contractility. Functional abnormalities in P311-/- mice resulted from decreased total and active levels of TGF-beta1, TGF-beta2, and TGF-beta3 that arise as a specific consequence of decreased translation. Vascular hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-beta1-TGF-beta3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF-beta1-TGF-beta3 and subsequent hypertension. Consistent with findings attained in mouse models, arteries recovered from hypertensive human patients displayed increased P311 expression. Thus, we identified P311 as the first protein known to modulate TGF-beta translation and the first pan-regulator of TGF-beta expression under steady-state conditions. Together, our findings point to P311 as a critical blood pressure regulator and establish a potential link between P311 expression and the development of hypertensive disease.
Keywords: Animals; Aorta/pathology/physiopathology; Aortography; Blood Pressure; Cells, Cultured; Female; Gene Expression; Gene Expression Regulation; Homeostasis; Humans; Hypotension/genetics/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle Contraction; Muscle, Smooth, Vascular/pathology/physiopathology; Myocytes, Smooth Muscle/metabolism; Nerve Tissue Proteins/genetics/metabolism; RNA, Messenger/genetics/metabolism; Transforming Growth Factor beta/genetics/metabolism/physiology; Up-Regulation; rho GTP-Binding Proteins/metabolism; Molecular Pharmacology
Journal Title: The Journal of clinical investigation
Volume: 123
Issue: 10
ISSN: 1558-8238; 0021-9738
Publisher: Unknown  
Journal Place: United States
Date Published: 2013
Start Page: 4502
End Page: 4512
Language: eng
DOI/URL:

10.1172/JCI69884
Notes: LR: 20131201; GR: HL-48730/HL/NHLBI NIH HHS/United States; GR: HL-77514/HL/NHLBI NIH HHS/United States; GR: HL-78752/HL/NHLBI NIH HHS/United States; JID: 7802877; 0 (Nerve Tissue Proteins); 0 (P311 protein, mouse); 0 (RNA, Messenger); 0 (Transforming Growth Factor beta); EC 3.6.5.2 (RhoA protein, mouse); EC 3.6.5.2 (rho GTP-Binding Proteins); OID: NLM: PMC3784545; 2013/03/14 [received]; 2013/07/18 [accepted]; 2013/09/16 [aheadofprint]; 2013/09/16 [epublish]; ppublish