Suppressor of cytokine signaling-3 and intimal hyperplasia in porcine coronary arteries following coronary intervention

Gaurav K. Gupta, Kajari Dhar, Michael Del Core, William J. Hunter, Georgios I. Hatzoudis, Devendra K. Agrawal

Research output: Contribution to journalArticle

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Abstract

Aims: The growth and differentiation of cells is regulated by cytokines by binding to cell-surface receptors and activating intracellular signal transduction cascade. Suppressor of cytokine signaling (SOCS)-3 is a negative regulator of cytokines. In this study we examined the expression of SOCS-3 in porcine coronary artery smooth muscle cells (PCASMCs) in vitro and in proliferating smooth muscle cells of neointimal lesions after coronary artery intervention in a swine model. Methods and results: PCASMCs were cultured and stimulated with TNF-α and/or IGF-1 individually or in combination. Protein expression of SOCS-3 was examined using Western blot. For in vivo studies, six female Yucatan miniswine were fed with special high cholesterol diet for 8. months. At 4. months of high cholesterol diet, animals underwent coronary balloon angioplasty. At the end of 8. months animals were euthanized, coronary arteries were isolated and morphological and histological studies were performed. Western blot data revealed significantly high SOCS-3 expression in PCASMCs in the presence of either TNF-α or IGF-1 (5-6 fold) alone. However, in the presence of both TNF-α and IGF-1 the SOCS-3 expression was significantly decreased (4-5 fold). Results from morphological studies including, H&E and Masson's trichrome stain showed typical lesions with significant neointimal proliferation. Histological evaluation showed expression of smooth muscle α-actin and significantly increased proliferating cell nuclear antigen (PCNA) in neointimal lesion. Interestingly, there was significantly decreased expression of SOCS-3 in smooth muscle cells of neointima as compared to control. Conclusions: These data suggest that SOCS-3 expression is decreased in proliferating smooth muscle cells of neointimal lesions. This leads to uncontrolled growth of vascular smooth muscle cells in injured arteries leading to restenosis. Therefore, local delivery of SOCS-3 gene at the site of injury after coronary artery intervention could regulate the proliferation of vascular smooth muscle cells and help in preventing the neointimal hyperplasia and restenosis.

Original languageEnglish
Pages (from-to)346-352
Number of pages7
JournalExperimental and Molecular Pathology
Volume91
Issue number1
DOIs
StatePublished - Aug 2011

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Tunica Intima
Hyperplasia
Coronary Vessels
Smooth Muscle Myocytes
Swine
Muscle
Cytokines
Cells
Insulin-Like Growth Factor I
Vascular Smooth Muscle
Nutrition
Western Blotting
Cholesterol
Animals
Diet
Neointima
Coronary Balloon Angioplasty
Signal transduction
Proliferating Cell Nuclear Antigen
Cell Surface Receptors

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

Suppressor of cytokine signaling-3 and intimal hyperplasia in porcine coronary arteries following coronary intervention. / Gupta, Gaurav K.; Dhar, Kajari; Del Core, Michael; Hunter, William J.; Hatzoudis, Georgios I.; Agrawal, Devendra K.

In: Experimental and Molecular Pathology, Vol. 91, No. 1, 08.2011, p. 346-352.

Research output: Contribution to journalArticle

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