LDL in patients with subclinical hypothyroidism shows increased lipid peroxidation

Lipids in Health and Disease

Chao Xu⁴  Ling Gao⁴  Jiajun Zhao⁴  Yunjia Wang⁴  Bei Wang⁵  Yan Zhang⁶  Bingchang Zhang⁷  Aihong Wang²  Changting Zuo¹  Kexi Zha³ 

[1] Department of gynaecology and obstetrics, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong, China;Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong, China;Department of endocrinology, Shanghai Second People’s Hospital, Shanghai 250021, China;Institute of Endocrinology and metabolism, Shandong Academy of Clinical Medicine, 324, Jing 5 Rd, Jinan, Shandong, China;Department of Health Care, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, China;Department of endocrinology, Shuguang Hospital Baoshan Branch, Shanghai 250021, China;Clinical Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, Shandong, China

关键词: Low density lipoproteins;    Oxidative stress;    Subclinical hypothyroidism;   

Others  :  1233285
DOI  :  10.1186/s12944-015-0092-4

 received in 2015-03-16, accepted in 2015-08-06,  发布年份 2015

【 摘 要 】

Background

Population-based studies have demonstrated that subclinical hypothyroidism (SCH) is an independent risk factor for atherosclerosis (OR = 1.9). However, this connection cannot be entirely explained by dyslipidemia accompanied by SCH. Lipid peroxidation also plays an important role in the development of atherosclerosis. In this study, we aimed to evaluate oxidative stress in SCH patients, as measured according to concentrations of hydroxy-octadecadienoic acids (HODEs) and hydroxy-eicosatetraenoic acids (HETEs) in both plasma and low density lipoproteins (LDL).

Subjects and methods

The concentrations of HODEs and HETEs in both LDL and plasma were examined in euthyroid (n = 10), mild SCH (4.5 ≤ TSH <10 mU/L, n = 10), and significant SCH (TSH ≥ 10 mU/L, n = 10) subjects, using a liquid chromatograph-electrospray ionization- mass spectrometer. Then, we explored the relationship among LDL oxidation, TSH levels, and carotid intima-media thickness (IMT), a biomarker of subclinical atherosclerosis.

Results

Serum LDL-C levels and mean-IMT in the significant SCH group were higher than in the euthyroid group (p < 0.05). The HODE and HETE concentrations clearly increased in the significant SCH patients compared with the euthyroid subjects, but there was no difference between the mild SCH and euthyroid groups. Among all subjects, linear and significant positive correlations were identified between TSH and mean-IMT after adjustment for confounding factors (r = 0.480, p = 0.018). Both 9-HODE (r = 0.376, p = 0.041) and 13-HODE (r = 0.447, p = 0.013) in LDL were linearly and positively correlated with TSH. The concentrations of HODEs (both 9-HODE and 13-HODE) in LDL were much higher in the thickened IMT group than in the normal IMT group (p = 0.017 and 0.015, respectively). HODEs in LDL were also positively associated with mean-IMT.

Conclusions

Our findings showed that lipid peroxidation was higher in the significant SCH patients than in the euthyroid subjects, which suggested that qualitative as well as quantitative changes in serum lipids resulting from SCH may add to atherosclerosis risk.

【 授权许可】

   
2015 Zha et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】

• [1]Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham Survey cohort. J Clin Endocrinol Metab. 2010; 95:1734-1740.
• [2]Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, Michelangeli V. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med. 2005; 165:2467-2472.
• [3]Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH et al.. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010; 304:1365-1374.
• [4]Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med. 2000; 132:270-278.
• [5]MacMahon SW, Cutler JA, Furberg CD, Payne GH. The effects of drug treatment for hypertension on morbidity and mortality from cardiovascular disease: a review of randomized controlled trials. Prog Cardiovasc Dis. 1986; 29:99-118.
• [6]Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000; 160:526-534.
• [7]Hueston WJ, Pearson WS. Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann Fam Med. 2004; 2:351-355.
• [8]Imaizumi S, Grijalva V, Navab M, Van Lenten BJ, Wagner AC, Anantharamiah GM, Fogelman AM, Reddy ST. L-4 F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL in mice. Drug Metab Lett. 2010; 4:139-148.
• [9]Yin H, Zhou Y, Zhu M, Hou S, Li Z, Zhong H, Lu J, Meng T, Wang J, Xia L et al.. Role of mitochondria in programmed cell death mediated by arachidonic acid-derived eicosanoids. Mitochondrion. 2013; 13:209-224.
• [10]Vangaveti V, Baune BT, Kennedy RL. Hydroxyoctadecadienoic acids: novel regulators of macrophage differentiation and atherogenesis. Ther Adv Endocrinol Metab. 2010; 1:51-60.
• [11]Wigren J, Surapureddi S, Olsson AG, Glass CK, Hammarstrom S, Soderstrom M. Differential recruitment of the coactivator proteins CREB-binding protein and steroid receptor coactivator-1 to peroxisome proliferator-activated receptor gamma/9-cis-retinoic acid receptor heterodimers by ligands present in oxidized low-density lipoprotein. J Endocrinol. 2003; 177:207-214.
• [12]Geng H, Zhang X, Wang C, Zhao M, Yu C, Zhang B, et al. Even mildly elevated TSH is associated with an atherogenic lipid profile in postmenopausal women with subclinical hypothyroidism. Endocr Res. 2014.
• [13]Bauer M, Caviezel S, Teynor A, Erbel R, Mahabadi AA, Schmidt-Trucksass A. Carotid intima-media thickness as a biomarker of subclinical atherosclerosis. Swiss Med Wkly. 2012; 142:w13705.
• [14]Kathuria C, Molinari F, Suri J. Atherosclerosis Disease Management. Springer, Berlin; 2010.
• [15]Vierhapper H, Nardi A, Grosser P, Raber W, Gessl A. Low-density lipoprotein cholesterol in subclinical hypothyroidism. Thyroid. 2000; 10:981-984.
• [16]Santi A, Duarte MM, de Menezes CC, Loro VL. Association of lipids with oxidative stress biomarkers in subclinical hypothyroidism. Int J Endocrinol. 2012; 2012:856359.
• [17]Torun AN, Kulaksizoglu S, Kulaksizoglu M, Pamuk BO, Isbilen E, Tutuncu NB. Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol (Oxf). 2009; 70:469-474.
• [18]Haribabu A, Reddy VS, Pallavi C, Bitla AR, Sachan A, Pullaiah P, Suresh V, Rao PV, Suchitra MM. Evaluation of protein oxidation and its association with lipid peroxidation and thyrotropin levels in overt and subclinical hypothyroidism. Endocrine. 2013; 44:152-157.
• [19]Mutlu S, Parlak A, Aydogan U, Aydogdu A, Soykut B, Akay C, et al. The effect of levothyroxine replacement therapy on lipid profile and oxidative stress parameters in patients with subclinical hypothyroid. Arch Pharm Res. 2013.
• [20]Wang D, Strandgaard S, Iversen J, Wilcox CS. Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension. Am J Physiol Regul Integr Comp Physiol. 2009; 296:R195-200.
• [21]Colas R, Sassolas A, Guichardant M, Cugnet-Anceau C, Moret M, Moulin P, Lagarde M, Calzada C. LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets. Diabetologia. 2011; 54:2931-2940.
• [22]Esterbauer H, Gebicki J, Puhl H, Jurgens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med. 1992; 13:341-390.
• [23]Spiteller P, Spiteller G. 9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE): excellent markers for lipid peroxidation. Chem Phys Lipids. 1997; 89:131-139.
• [24]Jira W, Spiteller G, Carson W, Schramm A. Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients. Chem Phys Lipids. 1998; 91:1-11.
• [25]Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell. 1998; 93:229-240.
• [26]Han KH, Chang MK, Boullier A, Green SR, Li A, Glass CK, Quehenberger O. Oxidized LDL reduces monocyte CCR2 expression through pathways involving peroxisome proliferator-activated receptor gamma. J Clin Invest. 2000; 106:793-802.
• [27]Proudfoot JM, Barden AE, Loke WM, Croft KD, Puddey IB, Mori TA. HDL is the major lipoprotein carrier of plasma F2-isoprostanes. J Lipid Res. 2009; 50:716-722.
• [28]Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA et al.. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004; 291:228-238.
• [29]Zhang X, Shao S, Geng H, Yu Y, Wang C, Liu Z, Yu C, Jiang X, Deng Y, Gao L, Zhao J. Expression profiles of six circulating microRNAs critical to atherosclerosis in patients with subclinical hypothyroidism: a clinical study. J Clin Endocrinol Metab. 2014; 99:E766-774.
• [30]Pauletto P, Palatini P, Da Ros S, Pagliara V, Santipolo N, Baccillieri S, Casiglia E, Mormino P, Pessina AC. Factors underlying the increase in carotid intima-media thickness in borderline hypertensives. Arterioscler Thromb Vasc Biol. 1999; 19:1231-1237.
• [31]Colas R, Pruneta-Deloche V, Guichardant M, Luquain-Costaz C, Cugnet-Anceau C, Moret M, Vidal H, Moulin P, Lagarde M, Calzada C. Increased lipid peroxidation in LDL from type-2 diabetic patients. Lipids. 2010; 45:723-731.
• [32]Yin H, Davis T, Porter NA. Simultaneous analysis of multiple lipid oxidation products in vivo by liquid chromatographic-mass spectrometry (LC-MS). Methods Mol Biol. 2010; 610:375-386.