The Effect of CYP1A1 and GSTP1 Isozymes on the Occurrence of Aortic Aneurysms

Abstract

Background Aortic aneurysms are vascular diseases that are associated with high mortality and morbidity. Cytochrome P450 CYP1A1 and glutathione S-transferase (GSTP1) isozymes were searched and compared with the patients who had experienced aortic surgery due to aortic aneurysm and atherosclerotic patients without aneurysm to find the relation of the oxidative stress with the aneurysms.

Materials and Methods Study group consisted of the patients with the diagnosis of aortic aneurysm (group I, n: 12) and control group who were operated for coronary bypass surgery: preoperatively drug users (group II, n: 21) and nonusers (group III, n: 15). Paraffin sections (4 μm thick) of aortic biopsy materials were stained with hematoxylin and eosine, CYP1A1 and GSTP1 immunohistochemical markers. The specimens were evaluated using light microscopy at 40- to 400-fold magnification.

Results The expressions of CYP1A1 and GSTP1 isozymes were found statistically significantly higher in the patients who have an aortic aneurysm than both the control groups (p < 0.05). There was no significant association between protein expressions, drugs and duration of usage, patient's demographic variables, and smoking (p > 0.05).

Conclusions In this pioneering study, CYP1A1 and GSTP1 isozymes are related with the aneurysms. The strategy that prevents the oxidative stress for the patients who had aortic aneurysms could be a valuable choice of searching to effect the aneurysmal progression.

Keywords

aortic aneurysm - aorta/aortic - artery/arteries - coronary bypass surgery - CYP1A1 - GSTP1 - vascular disease

Note

This article was presented at the 14th Congress of Asian Society for Vascular Surgery on October 26 to 29, 2013.

• References

• 1 Sakalihasan N, Limet R, Defawe OD. Abdominal aortic aneurysm. Lancet 2005; 365 (9470) 1577-1589
• 2 McCormick ML, Gavrila D, Weintraub NL. Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 2007; 27 (3) 461-469
• 3 Satriano JA, Shuldiner M, Hora K, Xing Y, Shan Z, Schlondorff D. Oxygen radicals as second messengers for expression of the monocyte chemoattractant protein, JE/MCP-1, and the monocyte colony-stimulating factor, CSF-1, in response to tumor necrosis factor-alpha and immunoglobulin G. Evidence for involvement of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase. J Clin Invest 1993; 92 (3) 1564-1571
• 4 Thier R, Brüning T, Roos PH , et al. Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GST genes. Int J Hyg Environ Health 2003; 206 (3) 149-171
• 5 Berk BC. Redox signals that regulate the vascular response to injury. Thromb Haemost 1999; 82 (2) 810-817
• 6 Wong PS, Eiserich JP, Reddy S, Lopez CL, Cross CE, van der Vliet A. Inactivation of glutathione S-transferases by nitric oxide-derived oxidants: exploring a role for tyrosine nitration. Arch Biochem Biophys 2001; 394 (2) 216-228
• 7 Swain JA, Darley-Usmar V, Gutteridge JM. Peroxynitrite releases copper from caeruloplasmin: implications for atherosclerosis. FEBS Lett 1994; 342 (1) 49-52
• 8 Zou MH, Ullrich V. Peroxynitrite formed by simultaneous generation of nitric oxide and superoxide selectively inhibits bovine aortic prostacyclin synthase. FEBS Lett 1996; 382 (1–2) 101-104
• 9 MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys 1999; 366 (1) 82-88
• 10 Oguztuzun S, Iscan M, Ozhavzali M, Sak SD. Comparison of GST isoenzyme expression in normal neoplastic breast tissue: Correlation with clinical and prognostic factors. Turk J Biol 2009; 33: 89-100
• 11 Schmidt JV, Bradfield CA. Ah receptor signaling pathways. Annu Rev Cell Dev Biol 1996; 12: 55-89
• 12 Willey JC, Coy EL, Frampton MW , et al. Quantitative RT-PCR measurement of cytochromes p450 1A1, 1B1, and 2B7, microsomal epoxide hydrolase, and NADPH oxidoreductase expression in lung cells of smokers and nonsmokers. Am J Respir Cell Mol Biol 1997; 17 (1) 114-124
• 13 Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005; 45: 51-88
• 14 Yajima N, Masuda M, Miyazaki M, Nakajima N, Chien S, Shyy JY. Oxidative stress is involved in the development of experimental abdominal aortic aneurysm: a study of the transcription profile with complementary DNA microarray. J Vasc Surg 2002; 36 (2) 379-385
• 15 Gil L, Adonis M. Genomics and proteomics offers new hopes towards a personalized approach to lung cancer prevention and treatment. Electron J Biotechnol 2003; 6 (3) 168-173
• 16 Dubick MA, Hunter GC, Casey SM, Keen CL. Aortic ascorbic acid, trace elements, and superoxide dismutase activity in human aneurysmal and occlusive disease. Proc Soc Exp Biol Med 1987; 184 (2) 138-143
• 17 Dubick MA, Keen CL, DiSilvestro RA, Eskelson CD, Ireton J, Hunter GC. Antioxidant enzyme activity in human abdominal aortic aneurysmal and occlusive disease. Proc Soc Exp Biol Med 1999; 220 (1) 39-45