Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet

Harald Mangge, Florian Prüller, Sieglinde Zelzer, Herwig Ainödhofer, Sabine Pailer, Petra Kieslinger, Johannes Haybaeck, Barbara Obermayer-Pietsch, Gerhard Cvirn, Hans-Jürgen Gruber, Harald Mangge, Florian Prüller, Sieglinde Zelzer, Herwig Ainödhofer, Sabine Pailer, Petra Kieslinger, Johannes Haybaeck, Barbara Obermayer-Pietsch, Gerhard Cvirn, Hans-Jürgen Gruber

Abstract

Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased-and hyperthyroid animals significantly decreased-ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.

Keywords: Sprague Dawley rats; endogenous thrombin potential (ETP); fat feeding; hyperthyroidism; hypothyroidism.

Figures

Figure 1
Figure 1
Levels of endogenous thrombin potential within the different treatment groups of hypo-, normo-, and hyperthyreote rats. Rats with hypothyreosis who receive a high fat diet show by far the highest endogenous thrombin potential levels. Hypothyroid rats under normal diet have also significantly increased endogenous thrombin potential levels compared to the euthyreote control group.

References

    1. Bubber P., Chauhan A., Sharma A., Bubber N., Bansal D.D. Effect of thyroxine on fibrinolytic system in rat. Indian J. Physiol. Pharmacol. 2012;56:267–272.
    1. Duntas L.H., Wartofsky L. Cardiovascular risk and subclinical hypothyroidism: Focus on lipids and new emerging risk factors. What is the evidence? Thyroid. 2007;17:1075–1084. doi: 10.1089/thy.2007.0116.
    1. Biondi B., Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004;24:1–13. doi: 10.1385/ENDO:24:1:001.
    1. Horacek J., Maly J., Svilias I., Smolej L., Cepkova J., Vizda J., Sadilek P., Fatorova I., Zak P. Prothrombotic changes due to an increase in thyroid hormone levels. Eur. J. Endocrinol. 2015;172:537–542. doi: 10.1530/EJE-14-0801.
    1. Chen Q., Yan Y., Zhang L., Cheng K., Liu Y., Zhu W. Effect of hyperthyroidism on the hypercoagulable state and thromboembolic events in patients with atrial fibrillation. Cardiology. 2014;127:176–182. doi: 10.1159/000356954.
    1. Lippi G., Franchini M., Targher G., Montagnana M., Salvagno G.L., Guidi G.C., Favaloro E.J. Hyperthyroidism is associated with shortened APTT and increased fibrinogen values in a general population of unselected outpatients. J. Thromb. Thrombolysis. 2009;28:362–365. doi: 10.1007/s11239-008-0269-z.
    1. Squizzato A., Romualdi E., Buller H.R., Gerdes V.E. Clinical review: Thyroid dysfunction and effects on coagulation and fibrinolysis: A systematic review. J. Clin. Endocrinol. Metab. 2007;92:2415–2420. doi: 10.1210/jc.2007-0199.
    1. Jabbar A., Razvi S. Thyroid disease and vascular risk. Clin. Med. 2014;14(Suppl. 6):S29–S32. doi: 10.7861/clinmedicine.14-6-s29.
    1. Pruller F., Raggam R.B., Posch V., Almer G., Truschnig-Wilders M., Horejsi R., Moller R., Weghuber D., Ille R., Schnedl W., et al. Trunk weighted obesity, cholesterol levels and low grade inflammation are main determinants for enhanced thrombin generation. Atherosclerosis. 2012;220:215–218. doi: 10.1016/j.atherosclerosis.2011.09.035.
    1. Sanchez C., Poggi M., Morange P.E., Defoort C., Martin J.C., Tanguy S., Dutour A., Grino M., Alessi M.C. Diet modulates endogenous thrombin generation, a biological estimate of thrombosis risk, independently of the metabolic status. Arterioscler. Thromb. Vasc. Biol. 2012;32:2394–2404. doi: 10.1161/ATVBAHA.112.250332.
    1. Schneider J.G., Isermann B., Kleber M.E., Wang H., Boehm B.O., Grammer T.B., Prueller F., Nawroth P.P., Maerz W. Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Int. J. Cardiol. 2014;176:139–144. doi: 10.1016/j.ijcard.2014.07.026.
    1. Tobias D.K., Pan A., Jackson C.L., O’Reilly E.J., Ding E.L., Willett W.C., Manson J.E., Hu F.B. Body-mass index and mortality among adults with incident type 2 diabetes. N. Engl. J. Med. 2014;370:233–244. doi: 10.1056/NEJMoa1304501.
    1. Seehaus S., Shahzad K., Kashif M., Vinnikov I.A., Schiller M., Wang H., Madhusudhan T., Eckstein V., Bierhaus A., Bea F., et al. Hypercoagulability inhibits monocyte transendothelial migration through protease-activated receptor-1-, phospholipase-Cβ-, phosphoinositide 3-kinase-, and nitric oxide-dependent signaling in monocytes and promotes plaque stability. Circulation. 2009;120:774–784. doi: 10.1161/CIRCULATIONAHA.109.849539.
    1. Boyle J.J., Johns M., Lo J., Chiodini A., Ambrose N., Evans P.C., Mason J.C., Haskard D.O. Heme induces heme oxygenase 1 via NRF2: Role in the homeostatic macrophage response to intraplaque hemorrhage. Arterioscler. Thromb. Vasc. Biol. 2011;31:2685–2691. doi: 10.1161/ATVBAHA.111.225813.
    1. Sadrzadeh S.M., Graf E., Panter S.S., Hallaway P.E., Eaton J.W. Hemoglobin. A biologic Fenton reagent. J. Biol. Chem. 1984;259:14354–14356.
    1. Ardissino D., Merlini P.A., Bauer K.A., Galvani M., Ottani F., Franchi F., Bertocchi F., Rosenberg R.D., Mannucci P.M. Coagulation activation and long-term outcome in acute coronary syndromes. Blood. 2003;1:2731–2735. doi: 10.1182/blood-2002-03-0954.
    1. Ragginer C., Bernecker C., Ainoedhofer H., Pailer S., Kieslinger P., Truschnig-Wilders M., Gruber H.J. Treatment with the nitric oxide donor SNP increases triiodothyronine levels in hyper- and hypothyroid Sprague-Dawley rats. Horm. Metab. Res. 2013;45:808–812. doi: 10.1055/s-0033-1349892.
    1. McAllister R.M., Albarracin I., Price E.M., Smith T.K., Turk J.R., Wyatt K.D. Thyroid status and nitric oxide in rat arterial vessels. J. Endocrinol. 2005;185:111–119. doi: 10.1677/joe.1.06022.
    1. Messarah M., Saoudi M., Boumendjel A., Boulakoud M.S., Feki A.E. Oxidative stress induced by thyroid dysfunction in rat erythrocytes and heart. Environ. Toxicol. Pharmacol. 2011;31:33–41. doi: 10.1016/j.etap.2010.09.003.
    1. Weltman N.Y., Ojamaa K., Savinova O.V., Chen Y.F., Schlenker E.H., Zucchi R., Saba A., Colligiani D., Pol C.J., Gerdes A.M. Restoration of cardiac tissue thyroid hormone status in experimental hypothyroidism: A dose-response study in female rats. Endocrinology. 2013;154:2542–2552. doi: 10.1210/en.2012-2087.
    1. Li W., Wang D., Song G., Zuo C., Qiao X., Qin S. The effect of combination therapy of allicin and fenofibrate on high fat diet-induced vascular endothelium dysfunction and liver damage in rats. Lipids Health Dis. 2010;9:131. doi: 10.1186/1476-511X-9-131.
    1. Bhandari U., Kumar V., Khanna N., Panda B.P. The effect of high-fat diet-induced obesity on cardiovascular toxicity in Wistar albino rats. Hum. Exp. Toxicol. 2011;30:1313–1321. doi: 10.1177/0960327110389499.
    1. Nadal-Casellas A., Proenza A.M., Gianotti M., Llad I. Brown adipose tissue redox status in response to dietary-induced obesity-associated oxidative stress in male and female rats. Stress. 2011;14:174–184.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe