Restoration of Endothelial Function in Pparα−/− Mice by Tempol
Peroxisome proliferator activated receptor alpha (PPARα) is one of the PPAR isoforms belonging to the nuclear hormone receptor superfamily that regulates genes involved in lipid and lipoprotein metabolism. PPARα is present in the vascular wall and is thought to be involved in protection against vasc...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2015/728494 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849396226840068096 |
|---|---|
| author | Neerupma Silswal Nikhil Parelkar Jon Andresen Michael J. Wacker |
| author_facet | Neerupma Silswal Nikhil Parelkar Jon Andresen Michael J. Wacker |
| author_sort | Neerupma Silswal |
| collection | DOAJ |
| description | Peroxisome proliferator activated receptor alpha (PPARα) is one of the PPAR isoforms belonging to the nuclear hormone receptor superfamily that regulates genes involved in lipid and lipoprotein metabolism. PPARα is present in the vascular wall and is thought to be involved in protection against vascular disease. To determine if PPARα contributes to endothelial function, conduit and cerebral resistance arteries were studied in Pparα−/− mice using isometric and isobaric tension myography, respectively. Aortic contractions to PGF2α and constriction of middle cerebral arteries to phenylephrine were not different between wild type (WT) and Pparα−/−; however, relaxation/dilation to acetylcholine (ACh) was impaired. There was no difference in relaxation between WT and Pparα−/− aorta to treatment with a nitric oxide (NO) surrogate indicating impairment in endothelial function. Endothelial NO levels as well as NO synthase expression were reduced in Pparα−/− aortas, while superoxide levels were elevated. Two-week feeding with the reactive oxygen species (ROS) scavenger, tempol, normalized ROS levels and rescued the impaired endothelium-mediated relaxation in Pparα−/− mice. These results suggest that Pparα−/− mice have impaired endothelial function caused by decreased NO bioavailability. Therefore, activation of PPARα receptors may be a therapeutic target for maintaining endothelial function and protection against cardiovascular disease. |
| format | Article |
| id | doaj-art-b4a7a5dbd6dd47dda2189d8656ecc48a |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-b4a7a5dbd6dd47dda2189d8656ecc48a2025-08-20T03:39:23ZengWileyPPAR Research1687-47571687-47652015-01-01201510.1155/2015/728494728494Restoration of Endothelial Function in Pparα−/− Mice by TempolNeerupma Silswal0Nikhil Parelkar1Jon Andresen2Michael J. Wacker3University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USAUniversity of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USAUniversity of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USAUniversity of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USAPeroxisome proliferator activated receptor alpha (PPARα) is one of the PPAR isoforms belonging to the nuclear hormone receptor superfamily that regulates genes involved in lipid and lipoprotein metabolism. PPARα is present in the vascular wall and is thought to be involved in protection against vascular disease. To determine if PPARα contributes to endothelial function, conduit and cerebral resistance arteries were studied in Pparα−/− mice using isometric and isobaric tension myography, respectively. Aortic contractions to PGF2α and constriction of middle cerebral arteries to phenylephrine were not different between wild type (WT) and Pparα−/−; however, relaxation/dilation to acetylcholine (ACh) was impaired. There was no difference in relaxation between WT and Pparα−/− aorta to treatment with a nitric oxide (NO) surrogate indicating impairment in endothelial function. Endothelial NO levels as well as NO synthase expression were reduced in Pparα−/− aortas, while superoxide levels were elevated. Two-week feeding with the reactive oxygen species (ROS) scavenger, tempol, normalized ROS levels and rescued the impaired endothelium-mediated relaxation in Pparα−/− mice. These results suggest that Pparα−/− mice have impaired endothelial function caused by decreased NO bioavailability. Therefore, activation of PPARα receptors may be a therapeutic target for maintaining endothelial function and protection against cardiovascular disease.http://dx.doi.org/10.1155/2015/728494 |
| spellingShingle | Neerupma Silswal Nikhil Parelkar Jon Andresen Michael J. Wacker Restoration of Endothelial Function in Pparα−/− Mice by Tempol PPAR Research |
| title | Restoration of Endothelial Function in Pparα−/− Mice by Tempol |
| title_full | Restoration of Endothelial Function in Pparα−/− Mice by Tempol |
| title_fullStr | Restoration of Endothelial Function in Pparα−/− Mice by Tempol |
| title_full_unstemmed | Restoration of Endothelial Function in Pparα−/− Mice by Tempol |
| title_short | Restoration of Endothelial Function in Pparα−/− Mice by Tempol |
| title_sort | restoration of endothelial function in pparα mice by tempol |
| url | http://dx.doi.org/10.1155/2015/728494 |
| work_keys_str_mv | AT neerupmasilswal restorationofendothelialfunctioninpparamicebytempol AT nikhilparelkar restorationofendothelialfunctioninpparamicebytempol AT jonandresen restorationofendothelialfunctioninpparamicebytempol AT michaeljwacker restorationofendothelialfunctioninpparamicebytempol |