title: Sonic hedgehog carried by microparticles corrects angiotensin II-induced hypertension and endothelial dysfunction in mice.
abstract: Microparticles are small fragments of the plasma membrane generated after cell stimulation. We recently showed that Sonic hedgehog (Shh) is present in microparticles generated from activated/apoptotic human T lymphocytes and corrects endothelial injury through nitric oxide (NO) release. This study investigates whether microparticles bearing Shh correct angiotensin II-induced hypertension and endothelial dysfunction in mice. Male Swiss mice were implanted with osmotic minipumps delivering angiotensin II (0.5 mg/kg/day) or NaCl (0.9%). Systolic blood pressure and heart rate were measured daily during 21 days. After 7 day of minipump implantation, mice received i.v. injections of microparticles (10 µg/ml) or i.p. Shh receptor antagonist cyclopamine (10 mg/kg/2 days) during one week. Angiotensin II induced a significant rise in systolic blood pressure without affecting heart rate. Microparticles reversed angiotensin II-induced hypertension, and cyclopamine prevented the effects of microparticles. Microparticles completely corrected the impairment of acetylcholine- and flow-induced relaxation in vessels from angiotensin II-infused mice. The improvement of endothelial function induced by microparticles was completely prevented by cyclopamine treatment. Moreover, microparticles alone did not modify NO and O2 . (-) production in aorta, but significantly increased NO and reduced O2. (-) productions in aorta from angiotensin II-treated mice, and these effects were blocked by cyclopamine. Altogether, these results show that microparticles bearing Shh correct angiotensin II-induced hypertension and endothelial dysfunction in aorta through a mechanism associated with Shh-induced NO production and reduction of oxidative stress. These microparticles may represent a new therapeutic approach in cardiovascular diseases associated with decreased NO production.
authors: LUNAM Université, Angers, France.
authors: Vannina González
authors: VG
authors: Marrachelli
authors: Maria Letizia
authors: ML
authors: Mastronardi
authors: Mamadou
authors: M
authors: Sarr
authors: Raffaella
authors: R
authors: Soleti
authors: Daniela
authors: D
authors: Leonetti
authors: María Carmen
authors: MC
authors: Martínez
authors: Ramaroson
authors: R
authors: Andriantsitohaina
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D000838:Anions / Q000378:metabolism; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003326:Coronary Circulation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D006339:Heart Rate; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D066298:In Vitro Techniques; D007260:Infusion Pumps; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism; D013599:Systole; D014664:Vasodilation
chemical_list: D000838:Anions; D053823:Hedgehog Proteins; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D000109:Acetylcholine
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