Document Detail

Vascular smooth muscle Emilin-1 is a regulator of arteriolar myogenic response and blood pressure.
MedLine Citation:
PMID:  22814752     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Emilin-1 is a protein of elastic extracellular matrix involved in blood pressure (BP) control by negatively affecting transforming growth factor (TGF)-β processing. Emilin1 null mice are hypertensive. This study investigates how Emilin-1 deals with vascular mechanisms regulating BP.
METHODS AND RESULTS: This study uses a phenotype rescue approach in which Emilin-1 is expressed in either endothelial cells or vascular smooth muscle cells of transgenic animals with the Emilin1(-/-) background. We found that normalization of BP required Emilin-1 expression in smooth muscle cells, whereas expression of the protein in endothelial cells did not modify the hypertensive phenotype of Emilin1(-/-) mice. We also explored the effect of treatment with anti-TGF-β antibodies on the hypertensive phenotype of Emilin1(-/-) mice, finding that neutralization of TGF-β in Emilin1 null mice normalized BP quite rapidly (2 weeks). Finally, we evaluated the vasoconstriction response of resistance arteries to perfusion pressure and neurohumoral agents in different transgenic mouse lines. Interestingly, we found that the hypertensive phenotype was coupled with an increased arteriolar myogenic response to perfusion pressure, while the vasoconstriction induced by neurohumoral agents remained unaffected. We further elucidate that, as for the hypertensive phenotype, the increased myogenic response was attributable to increased TGF-β activity.
CONCLUSIONS: Our findings clarify that Emilin-1 produced by vascular smooth muscle cells acts as a main regulator of resting BP levels by controlling the myogenic response in resistance arteries through TGF-β.
Gaia Litteri; Daniela Carnevale; Alessandra D'Urso; Giuseppe Cifelli; Paola Braghetta; Antonio Damato; Dario Bizzotto; Alessandro Landolfi; Francesco Da Ros; Patrizia Sabatelli; Nicola Facchinello; Angelo Maffei; Dino Volpin; Alfonso Colombatti; Giorgio M Bressan; Giuseppe Lembo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-19
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-16     Completed Date:  2012-10-29     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2178-84     Citation Subset:  IM    
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MeSH Terms
Antibodies, Neutralizing / administration & dosage
Arterioles / metabolism,  physiopathology
Blood Pressure* / drug effects,  genetics
Blood Pressure Monitoring, Ambulatory / methods
Dose-Response Relationship, Drug
Echocardiography, Doppler
Endothelial Cells / metabolism
Gene Expression Regulation
Hypertension / genetics,  metabolism*,  physiopathology
Membrane Glycoproteins / deficiency,  genetics,  metabolism*
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Muscle, Smooth, Vascular / drug effects,  metabolism*,  physiopathology
Nitric Oxide Synthase Type III / genetics,  metabolism
Time Factors
Transforming Growth Factor beta / immunology,  metabolism
Vasoconstriction* / drug effects,  genetics
Vasoconstrictor Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/Membrane Glycoproteins; 0/Transforming Growth Factor beta; 0/Vasoconstrictor Agents; 0/elastin microfibril interface located protein; EC Oxide Synthase Type III; EC protein, mouse

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