Down-regulation of vasoactive intestinal peptide and altered expression of its receptors in rat diabetic cardiomyopathy
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- down regulace * MeSH
- experimentální diabetes mellitus komplikace metabolismus patologie MeSH
- imunohistochemie MeSH
- kardiomyocyty metabolismus patologie MeSH
- kardiomyopatie etiologie metabolismus patologie MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus patologie MeSH
- peritoneální makrofágy metabolismus patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteinové prekurzory biosyntéza metabolismus MeSH
- radioimunoanalýza MeSH
- receptory vazoaktivního intestinálního peptidu typu I biosyntéza MeSH
- receptory vazoaktivního intestinálního peptidu typu II biosyntéza MeSH
- srdeční komory metabolismus MeSH
- vazoaktivní intestinální peptid biosyntéza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- proteinové prekurzory MeSH
- receptory vazoaktivního intestinálního peptidu typu I MeSH
- receptory vazoaktivního intestinálního peptidu typu II MeSH
- vazoaktivní intestinální peptid MeSH
Vasoactive intestinal peptide (VIP) is a vasorelaxant peptide that addresses two receptor subtypes, VPAC1 and VPAC2. It stimulates insulin secretion and mediates anti-inflammatory effects and has been proposed for treatment of type 2 and autoimmune diabetes. In the heart, VIP is produced and released primarily by intrinsic neurons and improves cardiac perfusion and function. Here, we investigated the involvement of this system in the events underlying development of experimentally induced diabetic cardiomyopathy. Rats received a single streptozotocin injection, and cardiac VIP content [radioimmune assay (RIA)], expression of the VIP precursors VPAC1 and VPAC2 [real-time reverse transcription-polymerase chain reaction (RT-PCR)], and VPAC1 and VPAC2 tissue distribution (immunohistochemistry) were assessed 4, 8, and 16 weeks thereafter and compared with corresponding vehicle-treated controls. Cardiac neuropathy manifests progressively during the first 4 months of diabetes at the preproVIP mRNA and VIP peptide level and is accompanied by initial down-regulation of VPAC2 at one prime target of VIP-containing axons, i.e., smooth muscle cells of coronary arterioles. VPAC1 is expressed by macrophages. After initial changes that are specific for atria and ventricles, respectively, VPAC1 and VPAC2 expression return to control levels at 16 weeks despite ongoing loss of VIP. Given the cardioprotective role of the VIP signaling system, the persistence of receptors has therapeutic implications since it is the prerequisite for trials with VPAC2 agonists.
Citace poskytuje Crossref.org
Substance P Receptor in the Rat Heart and Regulation of Its Expression in Long-Term Diabetes
