Evaluation of Cholesterol Synthesis and Absorption Pathways in Patients with Cardiovascular Diseases

Document Type : Original Article (s)

Authors

1 Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran

3 Professor, Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences AND Isfahan Cardiovascular Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Nowadays, coronary artery diseases (CADs) are among the most common diseases in societies. The aim of this study was to study the interplay between cholesterol absorption and synthesis in two groups of Iranian patients with CAD by measuring the markers of cholesterol synthesis and absorption pathways in plasma.Methods: The study population included 128 patients undergoing clinically indicated coronary angiography. Patients were divided into two groups after scoring the severity of their coronary stenosis; the S-stenosis group (patients with CAD, n = 75) had a significant stenosis indicated by coronary angiography, and the second group, N-stenosis (n = 55), had no significant coronary stenosis. Fasting plasma samples were used to measure cholesterol absorption and synthesis markers by gas chromatography-mass spectrometry (GC-MS).Findings: The level of cholesterol absorption markers in patients with coronary artery stenosis was slightly increased compared to patients without coronary artery stenosis, but this change was statistically significant only for cholestanol (P < 0.050). In terms of cholesterol synthesis markers, the results did not show any significant differences between the two groups (P > 0.050 for all).Conclusion: Study of cholesterol synthesis and absorption markers has not been reported in Iranian patients before. This article reports the results of such study for the first time. Considering the high prevalence of CADs and the importance of cholesterol metabolism in pathology of these diseases, the results may be used to understand some underlying mechanisms of development and progression of these diseases, and to manage the patient better.

Keywords

References

  1. Dawber TR, Moore FE, Mann GV. II. Coronary Heart Disease in the Framingham Study. Int J Epidemiol 2015; 44(6): 1767-80.
  2. Silbernagel G, Genser B, Nestel P, Marz W. Plant sterols and atherosclerosis. Curr Opin Lipidol 2013; 24(1): 12-7.
  3. Othman RA, Myrie SB, Jones PJ. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia. Atherosclerosis 2013; 231(2): 291-9.
  4. Phillips KM, Ruggio DM, Bailey JA. Precise quantitative determination of phytosterols, stanols, and cholesterol metabolites in human serum by capillary gas-liquid chromatography. J Chromatogr B Biomed Sci Appl 1999; 732(1): 17-29.
  5. Escurriol V, Cofan M, Moreno-Iribas C, Larranaga N, Martinez C, Navarro C, et al. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J Lipid Res 2010; 51(3): 618-24.
  6. Grundy SM, Ahrens EH, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res 1969; 10(3): 304-15.
  7. Hiramitsu S, Ishiguro Y, Matsuyama H, Yamada K, Kato K, Noba M, et al. The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia. J Atheroscler Thromb 2010; 17(1): 106-14.
  8. Simonen P, Gylling H, Miettinen TA. The validity of serum squalene and non-cholesterol sterols as surrogate markers of cholesterol synthesis and absorption in type 2 diabetes. Atherosclerosis 2008; 197(2): 883-8.
  9. Ahmida HS, Bertucci P, Franzo L, Massoud R, Cortese C, Lala A, et al. Simultaneous determination of plasmatic phytosterols and cholesterol precursors using gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring (SIM). J Chromatogr B Analyt Technol Biomed Life Sci 2006; 842(1): 43-7.
  10. Vinaixa M, Schymanski EL, Neumann S, Navarro M, Salek RM, Yanes O. Mass spectral databases for LC/MS- and GC/MS-based metabolomics: State of the field and future prospects. TrAC Trends in Analytical Chemistry 2016; 78: 23-35.
  11. Halket JM, Waterman D, Przyborowska AM, Patel RK, Fraser PD, Bramley PM. Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS. J Exp Bot 2005; 56(410): 219-43.
  12. Kelley RI. Diagnosis of Smith-Lemli-Opitz syndrome by gas chromatography/mass spectrometry of 7-dehydrocholesterol in plasma, amniotic fluid and cultured skin fibroblasts. Clin Chim Acta 1995; 236(1): 45-58.
  13. Booth GL, Kapral MK, Fung K, Tu JV. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: A population-based retrospective cohort study. Lancet 2006; 368(9529): 29-36.
  14. Wilson PW, Kannel WB, Silbershatz H, D'Agostino RB. Clustering of metabolic factors and coronary heart disease. Arch Intern Med 1999; 159(10): 1104-9.
  15. Bastien M, Poirier P, Lemieux I, Despres JP. Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis 2014; 56(4): 369-81.
  16. Subramanian S, Chait A. Hypertriglyceridemia secondary to obesity and diabetes. Biochim Biophys Acta 2012; 1821(5): 819-25.
  17. Miettinen TA, Gylling H, Strandberg T, Sarna S. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 1998; 316(7138): 1127-30.
  18. Ishibashi Y, Karino K, Yano S, Kijima T, Takahashi N, Yamagata S, et al. Relationship between cholesterol synthesis/absorption marker and vascular function in healthy subjects. Vascular Failure 2018; 2: 20-4.
  19. Weingartner O, Pinsdorf T, Rogacev KS, Blomer L, Grenner Y, Graber S, et al. The relationships of markers of cholesterol homeostasis with carotid intima-media thickness. PLoS One 2010; 5(10): e13467.
  20. Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich ) 2014; 16(1): 14-26.
  21. Silbernagel G, Fauler G, Renner W, Landl EM, Hoffmann MM, Winkelmann BR, et al. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J Lipid Res 2009; 50(2): 334-41.
  22. Herron KL, McGrane MM, Waters D, Lofgren IE, Clark RM, Ordovas JM, et al. The ABCG5 polymorphism contributes to individual responses to dietary cholesterol and carotenoids in eggs. J Nutr 2006; 136(5): 1161-5.
  23. Kastelein JJF, Akdim ES, Stroes AH, Zwinderman ML, Bots AF. Stalenhoef FL, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358: 1431-43.
  24. Miettinen TA, Strandberg TE, Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Arterioscler Thromb Vasc Biol 2000; 20(5): 1340-6.
  25. Matthan NR, Pencina M, LaRocque JM, Jacques PF, D'Agostino RB, Schaefer EJ, et al. Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res 2009; 50(9): 1927-35.
  26. Miettinen TA, Gylling H, Viikari J, Lehtimaki T, Raitakari OT. Synthesis and absorption of cholesterol in Finnish boys by serum non-cholesterol sterols: the cardiovascular risk in Young Finns Study. Atherosclerosis 2008; 200(1): 177-83.
Journal of Isfahan Medical School
Volume 37, Issue 523 - Serial Number 523
March and April 2019
Pages 385-391

Files

History

  • Receive Date: 13 December 2018
  • Revise Date: 02 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics