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Increased OPG expression and impaired OPG/TRAIL ratio in the aorta of diabetic rats
Mauro Vaccarezza1, Roberta Bortul, Roberto Fadda
1Department of Health and Motor Sciences, University of Cassino, Viale Bonomi, 03043 Cassino (FR), Italy. m.vaccarezza@unicas.it
Abstract:
Despite accumulating evidence showing that TNF-related apoptosis inducing ligand (TRAIL) plays a role in vascular biology and that its decoy receptor osteoprotegerin (OPG) is expressed in the vessel wall, modulation of these TNF and TNF-R family members in the early phases of diabetes mellitus has not been investigated. The expression of TRAIL and of OPG was examined both at the mRNA and protein levels in control and streptozotocin (SZT)-induced diabetic rats at early time points after the induction of diabetes mellitus. No differences in the steady-state mRNA levels of TRAIL were noticed by quantitative RT-PCR among the two groups of animals. On the other hand, diabetic rats showed a rapid and significant increase of the steady-state mRNA levels of OPG in the aortic wall of diabetic animals with respect to vehicle-treated (control) animals. These findings were confirmed at the protein level by analysing the amount of TRAIL and OPG proteins in aortic lysates by either Western blot or immunohistochemistry. Thus, an abnormal elevation of the OPG/TRAIL ratio in the vessel wall characterizes the early onset of diabetes mellitus and might represent a molecular mechanism involved in the vascular dysfunction characterizing diabetes mellitus.
Insights
Early diabetes mellitus in rats rapidly increases osteoprotegerin (OPG) mRNA and protein in the aorta, while TNF-related apoptosis inducing ligand (TRAIL) levels remain unchanged. This altered OPG/TRAIL ratio may drive vascular dysfunction in diabetes.
Area of Science:
- Vascular Biology
- Endocrinology
- Molecular Medicine
Background:
- TNF-related apoptosis inducing ligand (TRAIL) and its decoy receptor osteoprotegerin (OPG) are implicated in vascular biology.
- Their role in the early stages of diabetes mellitus remains largely uninvestigated.
Purpose of the Study:
- To investigate the modulation of TRAIL and OPG expression in the early phases of streptozotocin (SZT)-induced diabetes mellitus in rats.
- To determine if changes in OPG/TRAIL ratio contribute to early vascular dysfunction in diabetes.
Main Methods:
- Quantitative RT-PCR to assess mRNA levels of TRAIL and OPG in rat aortas.
- Western blot and immunohistochemistry to confirm protein levels of TRAIL and OPG.
- Comparison between control (vehicle-treated) and diabetic (SZT-induced) rat models.
Main Results:
- No significant difference in TRAIL mRNA levels between control and diabetic rats.
- A rapid and significant increase in OPG mRNA levels was observed in the aortic wall of diabetic rats compared to controls.
- Protein levels of OPG were elevated, while TRAIL levels remained comparable, in diabetic aortas, confirming mRNA findings.
Conclusions:
- Early diabetes mellitus is characterized by an abnormal elevation of the OPG/TRAIL ratio in the vessel wall.
- This altered ratio may represent a key molecular mechanism contributing to the vascular dysfunction observed in diabetes mellitus.
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