title: Chronic Treatment with Minoxidil Induces Elastic Fiber Neosynthesis and Functional Improvement in the Aorta of Aged Mice.
abstract: Normal arterial aging processes involve vascular cell dysfunction associated with wall stiffening, the latter being due to progressive elastin and elastic fiber degradation, and elastin and collagen cross-linking by advanced glycation end products (AGEs). These processes progressively lead to cardiovascular dysfunction during aging. Elastin is only synthesized during late gestation and childhood, and further degradation occurring throughout adulthood cannot be physiologically compensated by replacement of altered material. However, the ATP-dependent K+channel opener minoxidil has been shown to stimulate elastin expression in vitro and in vivo in the aorta of young adult rats. Therefore, we have studied the effect of a 10-week chronic oral treatment with minoxidil (120 mg/L in drinking water) on the aortic structure and function in aged 24-month-old mice. Minoxidil treatment increased tropoelastin, fibulin-5, and lysyl-oxidase messenger RNA levels, reinduced a moderate expression of elastin, and lowered the levels of AGE-related molecules. This was accompanied by the formation of newly synthesized elastic fibers, which had diverse orientations in the wall. A decrease in the glycation capacity of aortic elastin was also produced by minoxidil treatment. The ascending aorta also underwent a minoxidil-induced increase in diameter and decrease in wall thickness, which partly reversed the age-associated thickening and returned the wall thickness value and strain-stress relation closer to those of younger adult animals. In conclusion, our results suggest that minoxidil presents an interesting potential for arterial remodeling in an antiaging perspective, even when treating already aged animals.
authors.affiliation: 1 PVICSV-INSERM U882-iRTSV-CEA, Université Joseph Fourier , Grenoble, France .
authors.forename: Marion
authors.initials: M
authors.lastname: Coquand-Gandit
authors.affiliation: 2 INSERM, U1148, and Hôpital Bichat-Claude Bernard , Paris, France .
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Jacob
authors.affiliation: 1 PVICSV-INSERM U882-iRTSV-CEA, Université Joseph Fourier , Grenoble, France .|3 Université Grenoble Alpes , HP2, Grenoble, France .|4 INSERM U1042 , HP2, Grenoble, France .|5 CHU de Grenoble , HP2, Grenoble, France .
authors.forename: Wassim
authors.initials: W
authors.lastname: Fhayli
authors.affiliation: 6 Departments of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain; Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain .
authors.forename: Beatriz
authors.initials: B
authors.lastname: Romero
authors.affiliation: 7 Medical University of Pleven, Department of Biology, Pleven, Bulgaria .
authors.forename: Miglena
authors.initials: M
authors.lastname: Georgieva
authors.affiliation: 1 PVICSV-INSERM U882-iRTSV-CEA, Université Joseph Fourier , Grenoble, France .|8 BCI-BPCR-INSERM UMR_S1036-iRTSV-CEA, Université Grenoble Alpes , Grenoble, France .
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bouillot
authors.affiliation: 1 PVICSV-INSERM U882-iRTSV-CEA, Université Joseph Fourier , Grenoble, France .|3 Université Grenoble Alpes , HP2, Grenoble, France .|4 INSERM U1042 , HP2, Grenoble, France .|5 CHU de Grenoble , HP2, Grenoble, France .
authors.forename: Eric
authors.initials: E
authors.lastname: Estève
authors.affiliation: 9 IBS Platform of the Grenoble Instruct Center (ISBG: UMS 3518 CNRS-CEA- Université Grenoble Alpes -EMBL), Grenoble, France .
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Andrieu
authors.affiliation: 3 Université Grenoble Alpes , HP2, Grenoble, France .|4 INSERM U1042 , HP2, Grenoble, France .|5 CHU de Grenoble , HP2, Grenoble, France .
authors.forename: Sandrine
authors.initials: S
authors.lastname: Brasseur
authors.affiliation: 3 Université Grenoble Alpes , HP2, Grenoble, France .|4 INSERM U1042 , HP2, Grenoble, France .|5 CHU de Grenoble , HP2, Grenoble, France .
authors.forename: Sophie
authors.initials: S
authors.lastname: Bouyon
authors.affiliation: 6 Departments of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain; Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain .
authors.forename: Natalio
authors.initials: N
authors.lastname: Garcia-Honduvilla
authors.affiliation: 1 PVICSV-INSERM U882-iRTSV-CEA, Université Joseph Fourier , Grenoble, France .|8 BCI-BPCR-INSERM UMR_S1036-iRTSV-CEA, Université Grenoble Alpes , Grenoble, France .
authors.forename: Philippe
authors.initials: P
authors.lastname: Huber
authors.affiliation: 6 Departments of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain; Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain .
authors.forename: Julia
authors.initials: J
authors.lastname: Buján
authors.affiliation: 7 Medical University of Pleven, Department of Biology, Pleven, Bulgaria .
authors.forename: Milena
authors.initials: M
authors.lastname: Atanasova
authors.affiliation: 1 PVICSV-INSERM U882-iRTSV-CEA, Université Joseph Fourier , Grenoble, France .|3 Université Grenoble Alpes , HP2, Grenoble, France .|4 INSERM U1042 , HP2, Grenoble, France .|5 CHU de Grenoble , HP2, Grenoble, France .
authors.forename: Gilles
authors.initials: G
authors.lastname: Faury
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D001696:Biomechanical Phenomena / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004547:Elastic Tissue / Q000187:drug effects / Q000502:physiology*; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008914:Minoxidil / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D008914:Minoxidil; D003094:Collagen; D004549:Elastin
keywords: advanced glycation end products; aging; arteries; elastin; mechanics; minoxidil