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P311‐null mice are hypotensive due to a systemic decrease in TGF‐beta level and activity
Author(s) -
Badri Kameswara Rao,
Aramgam Sree Latha,
Dhru Urmil,
Cao Jun,
Schuger Lucia
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb483
Subject(s) - contractility , downregulation and upregulation , medicine , endocrinology , in vivo , contraction (grammar) , blood pressure , electrical impedance myography , vascular smooth muscle , homeostasis , biology , chemistry , smooth muscle , vasodilation , biochemistry , microbiology and biotechnology , gene
P311 is an 8 kDa protein highly expressed in brain and vascular smooth muscle (VSM). Telemetry and VPR tail cuff plethysmography demonstrated that p311 ‐null (P311 KO) mice exhibit pronounced systemic hypotension in the absence of phenotypic abnormalities. Myography and collagen gel contraction studies revealed a severe decrease in blood vessel and VSM cell contraction respectively. The hypofunctionality of the VSM contractile apparatus was confirmed by immunoblot analysis. Since we and others found that P311 is involved in TGF‐β regulation and since TGF‐β participates in blood pressure control, we determined the level and activity of TGF‐β in the VSM and blood of P311 KO mice. These studies revealed a significant downregulation in all TGF‐β1‐3 levels and activity. Treatment with exogenous recombinant TGF‐β1 or 3, but not TGF‐β2 partially rescued the defective contractile phenotype, whereas combined treatment restored normal contractility in vivo and in vitro. Our studies demonstrated that P311 controls the systemic levels and activity of TGF‐β1‐3 and thereby plays a critical role in vascular homeostasis. This work is supported by NHLBI.