title: Protection from cigarette smoke-induced vascular injury by recombinant human relaxin-2 (serelaxin).
abstract: Smoking is regarded as a major risk factor for the development of cardiovascular diseases (CVD). This study investigates whether serelaxin (RLX, recombinant human relaxin-2) endowed with promising therapeutic properties in CVD, can be credited of a protective effect against cigarette smoke (CS)-induced vascular damage and dysfunction. Guinea pigs exposed daily to CS for 8 weeks were treated with vehicle or RLX, delivered by osmotic pumps at daily doses of 1 or 10 μg. Controls were non-smoking animals. Other studies were performed on primary guinea pig aortic endothelial (GPAE) cells, challenged with CS extracts (CSE) in the absence and presence of 100 ng/ml (17 nmol/l) RLX. In aortic specimens from CS-exposed guinea pigs, both the contractile and the relaxant responses to phenylephrine and acetylcholine, respectively, were significantly reduced in amplitude and delayed, in keeping with the observed adverse remodelling of the aortic wall, endothelial injury and endothelial nitric oxide synthase (eNOS) down-regulation. RLX at both doses maintained the aortic contractile and relaxant responses to a control-like pattern and counteracted aortic wall remodelling and endothelial derangement. The experiments with GPAE cells showed that CSE significantly decreased cell viability and eNOS expression and promoted apoptosis by sparkling oxygen free radical-related cytotoxicity, while RLX counterbalanced the adverse effects of CSE. These findings demonstrate that RLX is capable of counteracting CS-mediated vascular damage and dysfunction by reducing oxidative stress, thus adding a tile to the growing mosaic of the beneficial effects of RLX in CVD.
authors.affiliation: Department of Experimental & Clinical Medicine, Section of Anatomy & Histology & Research Unit of Histology & Embryology, University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.affiliation: Department of Experimental & Clinical Medicine, Section of Anatomy & Histology & Research Unit of Histology & Embryology, University of Florence, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Boccalini
authors.affiliation: Section of Physiology, University of Florence, Florence, Italy.
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Baccari
authors.affiliation: Department of Experimental & Clinical Biomedical Sciences 'Mario Serio', Section of Biochemistry, University of Florence, Florence, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.affiliation: Section of Physiology, University of Florence, Florence, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Garella
authors.affiliation: Department of Experimental & Clinical Biomedical Sciences 'Mario Serio', Section of Biochemistry, University of Florence, Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.affiliation: Department of Experimental & Clinical Medicine, Section of Anatomy & Histology & Research Unit of Histology & Embryology, University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calosi
authors.affiliation: Department of Experimental & Clinical Medicine, Section of Anatomy & Histology & Research Unit of Histology & Embryology, University of Florence, Florence, Italy.
authors.forename: Daniele
authors.identifier: http://orcid.org/0000-0001-6302-901X
authors.initials: D
authors.lastname: Bani
authors.affiliation: Department of Experimental & Clinical Medicine, Section of Anatomy & Histology & Research Unit of Histology & Embryology, University of Florence, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D045424:Complex Mixtures / Q000633:toxicity*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006168:Guinea Pigs; D015918:Infusion Pumps, Implantable; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009995:Osmosis; D018384:Oxidative Stress; D010656:Phenylephrine / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012065:Relaxin / Q000494:pharmacology*; D014026:Nicotiana / Q000737:chemistry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D057772:Vascular System Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D045424:Complex Mixtures; D020011:Protective Agents; D011994:Recombinant Proteins; D014028:Tobacco Smoke Pollution; D010656:Phenylephrine; D009569:Nitric Oxide; D012065:Relaxin; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine
keywords: aorta; cigarette smoke; eNOS; oxidative stress; relaxin