Correlation between biopterin levels and intimal-media thickness in type-2 diabetic hypertensive patients

Journal of Diabetes & Metabolic Disorders

Bruno Alfonso Escalante-Acosta²  Montserrat Berenice Duran-Salgado⁴  Saul Huerta-Ramirez⁴  Alberto Maceda-Serrano⁴  Leonardo Del Valle-Mondragon¹  Hilda Vargas-Robles³  Alberto Francisco Rubio-Guerra⁴ 

[1] Departamento de Farmacología, Instituto Nacional de Cardiología “Ignacio Chávez”, México, Mexico;Centro de Investigación y de Estudios Avanzados del IPN, Monterrey, NL, Mexico;Centro de Investigación y de Estudios Avanzados del IPN, México, DF, Mexico;Hospital General de Ticomán SS and Mexican Group for Basic And Clinical Research in Internal Medicine, México, DF C.P. 03600, Mexico

关键词: Endothelial dysfunction;    BH4/BH2 ratio. intima-media thickness;    Dihydrobiopterin;    Tetrahydrobiopterin;   

Others  :  806565
DOI  :  10.1186/2251-6581-13-6

 received in 2013-08-14, accepted in 2013-11-11,  发布年份 2014

【 摘 要 】

Background

Biopterins have a crucial role in the function of nitric oxide synthase, uncoupling of the enzyme leads to endothelial dysfunction and vascular damage, The aim of this study was to evaluate the relationship between the levels of biopterins with carotid intima-media thickness (CIMT) in hypertensive type-2 diabetic patients.

Methods

We studied 30 hypertensive type-2 diabetic patients and 30 normotensive non-diabetic age-matched subjects, in whom biopterins levels were measured by reverse phase high performance liquid chromatography with fluorescence detection. Additionally, the CIMT of both the common and internal carotid arteries was measured. The levels of biopterins and CIMT were correlated using the Pearson correlation coefficient test.

Results

We did not find a significantly correlation between biopterins levels and CIMT. However, we found a significantly inverse correlation between the BH4/BH2 ratio and the CIMT in patients (r = -0.54, p < 0.01). A multiple regression analysis revealed that the CIMT correlated significantly and independently with the BH4/BH2 ratio.

Conclusion

Our results suggest that the BH4/BH2 ratio seems to be a better marker of vascular disease than biopterin levels.

【 授权许可】

   
2014 Rubio-Guerra et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Rubio-Guerra AF, Vargas-Robles H, Ramos-Brizuela LM, Escalante-Acosta BA: Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients? Integr Blood Press Control 2010, 3:125-132.
• [2]Cunnington C, Channon KM: Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology. Heart 2010, 96:1872-1877.
• [3]Noguchi K, Hamadate N, Matsuzaki T, Sakanashi M, Nakasone J, Uchida T, et al.: Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo. Am J Physiol Heart Circ Physiol 2011, 301:H721-H729.
• [4]Takeda M, Yamashita T, Shinohara M, Sasaki N, Takaya T, Nakajima K, et al.: Plasma tetrahydrobiopterin/dihydrobiopterin ratio. A posible marker of endothelial dysfunction. Cir J 2009, 73:955-962.
• [5]Mansouri M, Heshmat R, Tabatabaei-Malazy O, Sharifi F, Badamchizadeh Z, Alatab S, Omidfar K, Fakhrzadeh H, Larijani B: The association of carotid intima media thickness with retinol binding protein-4 and total and high molecular weight adiponectin in type 2 diabetic patients. J Diabetes Metab Disord 2012, 11:2. BioMed Central Full Text
• [6]American Diabetes Association: Standards of medical care in diabetes – 2011. Diabetes Care 2011, 34:S27.
• [7]Kotb NA, Gaber R, Salama M, Nagy HM, Elhendy A: Clinical and biochemical predictors of increased carotid intima-media thickness in overweight and obese adolescents with type 2 diabetes. Diab Vasc Dis Res 2012, 9:35-41.
• [8]Alp NJ, Channon KM: Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 2005, 24:413-420.
• [9]Rubio-Guerra AF, Vargas-Robles H, Del Valle-Mondragon L, Lozano-Nuevo JJ, Escalante-Acosta BA: Association between the levels of circulating adhesion molecules and biopterins in type-2 diabetic normotensive patients adhesion molecules and biopterins. Endocr Metab Immune Disord Drug Targets 2012, 12:243-246.
• [10]Rubio AF, Vargas H, Maceda A, Lozano JJ, Escalante BA: Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients. Cell Adh Migr 2009, 3:369-372.
• [11]Katusic ZS, D’Uscio L, Nath KA: Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects. Trends Pharmacol Sci 2009, 30:48-54.
• [12]Ueda S, Matsuoka H, Miyazaki H, Usui M, Okuda S, Imaizumi T: Tetrahydrobiopterin restores endothelial function in long-term smokers. J Am Coll Cardiol 2009, 35:71-75.
• [13]Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, et al.: Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation 2011, 124:335-345.