title: Vascular smooth muscle Emilin-1 is a regulator of arteriolar myogenic response and blood pressure.
abstract: 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.
  
  
  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.
authors: Department of Biomedical Sciences, University of Padova, Viale G. Colombo, 3, 35131 Padova, Italy.
authors: Gaia
authors: G
authors: Litteri
authors: Daniela
authors: D
authors: Carnevale
authors: Alessandra
authors: A
authors: D'Urso
authors: Giuseppe
authors: G
authors: Cifelli
authors: Paola
authors: P
authors: Braghetta
authors: Antonio
authors: A
authors: Damato
authors: Dario
authors: D
authors: Bizzotto
authors: Alessandro
authors: A
authors: Landolfi
authors: Francesco Da
authors: FD
authors: Ros
authors: Patrizia
authors: P
authors: Sabatelli
authors: Nicola
authors: N
authors: Facchinello
authors: Angelo
authors: A
authors: Maffei
authors: Dino
authors: D
authors: Volpin
authors: Alfonso
authors: A
authors: Colombatti
authors: Giorgio M
authors: GM
authors: Bressan
authors: Giuseppe
authors: G
authors: Lembo
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015150:Echocardiography, Doppler; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D013686:Telemetry; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D014662:Vasoconstrictor Agents; C030340:elastin microfibril interface located protein; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse