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Farnesyl Pyrophosphate Synthase Blocker Ibandronate Reduces Thoracic Aortic Fibrosis in Diabetic Rats.
- Source :
-
The American journal of the medical sciences [Am J Med Sci] 2019 Apr; Vol. 357 (4), pp. 323-332. Date of Electronic Publication: 2019 Jan 31. - Publication Year :
- 2019
-
Abstract
- Background: This study assessed the effect of ibandronate (IBN), a farnesyl pyrophosphate synthase (FPPS) inhibitor, on vascular remodeling in diabetic rats.<br />Methods: A rat model of diabetes was induced by a high-fat and high-sugar diet combined with a small dose of streptozotocin. The diabetic rats received 5 µg/kg of ibandronate solution or normal saline subcutaneously every morning for 16 weeks. The morphology of the thoracic aorta was assessed by hematoxylin and eosin and Masson's trichrome staining techniques. Gene expression levels of connective tissue growth factor (CTGF) and FPPS were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CTGF and FPPS protein levels were determined by Western blotting analysis.<br />Results: Rats with diabetes mellitus showed moderate hyperglycemia, insulin resistance, hyperlipidemia and thoracic aortic fibrosis. FPPS was significantly upregulated in the thoracic aorta from diabetic animals. Interestingly, IBN treatment for 16 weeks alleviated the diabetes-induced histopathologic changes in the thoracic aortic wall and reduced CTGF protein and mRNA levels.<br />Conclusions: These findings provided evidence that FPPS is involved in thoracic aortic fibrosis in diabetic rats. Meanwhile, IBN could alleviate vascular remodeling in diabetic animals.<br /> (Copyright © 2019. Published by Elsevier Inc.)
- Subjects :
- Animals
Aortic Diseases pathology
Diabetes Mellitus, Experimental etiology
Fibrosis pathology
Male
Rats
Rats, Sprague-Dawley
Aorta, Thoracic pathology
Aortic Diseases drug therapy
Fibrosis drug therapy
Geranyltranstransferase antagonists & inhibitors
Hypoglycemic Agents pharmacology
Ibandronic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-2990
- Volume :
- 357
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The American journal of the medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30904048
- Full Text :
- https://doi.org/10.1016/j.amjms.2019.01.014