Endothelin-mediated remodeling in aortas of diabetic rats

Gen Fukuda, Zia A. Khan, Yousef P. Barbin, Hana Farhangkhoee, Ronald Tilton, Subrata Chakrabarti

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Smooth muscle cells proliferation and extracellular matrix (ECM) protein deposition are key features of diabetic macroangiopathy. In the present study, we have studied the role of endothelinA (ETA) receptor, the predominant receptor on smooth muscle cells, in diabetes-induced vascular hypertrophy and remodeling. Methods: Streptozotocin-induced diabetic rats were administrated a selective ETA receptor antagonist, TBC3214, for 26 weeks. Following treatment, aortas were harvested and subjected to gene expression and morphometric analyses. We quantified fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) expression as indicators of increased ECM protein synthesis. ET-1, ET-3, transforming growth factor-β1 (TGF-β1) and angiotensinogen mRNA levels were measured to elucidate genes involved in FN expression. We have investigated an embryonic splice variant of FN, oncofetal FN, and nonmuscle myosin heavy chain (SMemb) as vascular remodeling indicators. Results: Our results show that diabetes leads to upregulation of FN, PAI-1, ET-1, ET-3, TGF-β1 and angiotensinogen mRNA levels in association with increased medial thickness. Immunohistochemical analyses revealed concurrent protein level changes. Diabetes also upregulated oncofetal FN and SMemb mRNA levels. Treatment with TBC3214 attenuated the mRNA levels of several genes and prevented increased medial thickness. Conclusions: These results indicate that diabetes-induced vascular hypertrophy and remodeling is associated with reexpression of embryonic forms of FN and myosin heavy chain. Such changes are ET-dependent and may be mediated via TGF-β1 and angiotensin.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalDiabetes/Metabolism Research and Reviews
Volume21
Issue number4
DOIs
StatePublished - Jul 2005

Fingerprint

Endothelins
Medical problems
Fibronectins
Aorta
Rats
Transforming Growth Factors
Angiotensinogen
Messenger RNA
Myosin Heavy Chains
Extracellular Matrix Proteins
Plasminogen Activator Inhibitor 1
Muscle
Genes
Hypertrophy
Smooth Muscle Myocytes
Angiotensins
Cell proliferation
Streptozocin
Gene expression
Cells

Keywords

  • Endothelins
  • Extracellular matrix
  • Macroangiopathy
  • Oncofetal fibronectin
  • SMemb

ASJC Scopus subject areas

  • Endocrinology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Fukuda, G., Khan, Z. A., Barbin, Y. P., Farhangkhoee, H., Tilton, R., & Chakrabarti, S. (2005). Endothelin-mediated remodeling in aortas of diabetic rats. Diabetes/Metabolism Research and Reviews, 21(4), 367-375. https://doi.org/10.1002/dmrr.527

Endothelin-mediated remodeling in aortas of diabetic rats. / Fukuda, Gen; Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Tilton, Ronald; Chakrabarti, Subrata.

In: Diabetes/Metabolism Research and Reviews, Vol. 21, No. 4, 07.2005, p. 367-375.

Research output: Contribution to journalArticle

Fukuda, G, Khan, ZA, Barbin, YP, Farhangkhoee, H, Tilton, R & Chakrabarti, S 2005, 'Endothelin-mediated remodeling in aortas of diabetic rats', Diabetes/Metabolism Research and Reviews, vol. 21, no. 4, pp. 367-375. https://doi.org/10.1002/dmrr.527
Fukuda G, Khan ZA, Barbin YP, Farhangkhoee H, Tilton R, Chakrabarti S. Endothelin-mediated remodeling in aortas of diabetic rats. Diabetes/Metabolism Research and Reviews. 2005 Jul;21(4):367-375. https://doi.org/10.1002/dmrr.527
Fukuda, Gen ; Khan, Zia A. ; Barbin, Yousef P. ; Farhangkhoee, Hana ; Tilton, Ronald ; Chakrabarti, Subrata. / Endothelin-mediated remodeling in aortas of diabetic rats. In: Diabetes/Metabolism Research and Reviews. 2005 ; Vol. 21, No. 4. pp. 367-375.
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