Limits...
Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease.

Meuwese CL, Olauson H, Qureshi AR, Ripsweden J, Barany P, Vermeer C, Drummen N, Stenvinkel P - PLoS ONE (2015)

Bottom Line: Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels.Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

View Article: PubMed Central - PubMed

Affiliation: Department of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT

Introduction: Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho.

Methods and material: In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively.

Results: fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.

Discussion: The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

No MeSH data available.


Related in: MedlinePlus

A hypothesis on the impact of non-thyroidal illness on vascular calcification.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492991&req=5

pone.0132353.g001: A hypothesis on the impact of non-thyroidal illness on vascular calcification.

Mentions: Recent in vitro studies have suggested functional links between thyroid hormones, MGP and Klotho. First, Sato et al.[16] observed that physiological concentrations of T3 facilitate MGP gene expression in smooth muscle cells, an effect that is likely mediated by thyroid hormone response element in the promotor region of the MGP gene.[16] Similarly, Klotho synthesis was reported to be under control of thyroid hormone stimulation.[17] These findings lead us to speculate that nonthyroidal illness could initiate an increased vascular calcification through down-regulation of the protective effects by MGP and Klotho (Fig 1). Therefore, we studied; 1) the association between thyroid hormone concentrations and (i) vascular calcification/arterial stiffness, (ii) sKlotho and (iii), MGP as well as; 2) the association of plasma MGP and sKlotho concentrations with surrogate markers of vascular calcification/arterial stiffness in a carefully phenotyped cohort of younger ESRD patients.


Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease.

Meuwese CL, Olauson H, Qureshi AR, Ripsweden J, Barany P, Vermeer C, Drummen N, Stenvinkel P - PLoS ONE (2015)

A hypothesis on the impact of non-thyroidal illness on vascular calcification.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492991&req=5

pone.0132353.g001: A hypothesis on the impact of non-thyroidal illness on vascular calcification.
Mentions: Recent in vitro studies have suggested functional links between thyroid hormones, MGP and Klotho. First, Sato et al.[16] observed that physiological concentrations of T3 facilitate MGP gene expression in smooth muscle cells, an effect that is likely mediated by thyroid hormone response element in the promotor region of the MGP gene.[16] Similarly, Klotho synthesis was reported to be under control of thyroid hormone stimulation.[17] These findings lead us to speculate that nonthyroidal illness could initiate an increased vascular calcification through down-regulation of the protective effects by MGP and Klotho (Fig 1). Therefore, we studied; 1) the association between thyroid hormone concentrations and (i) vascular calcification/arterial stiffness, (ii) sKlotho and (iii), MGP as well as; 2) the association of plasma MGP and sKlotho concentrations with surrogate markers of vascular calcification/arterial stiffness in a carefully phenotyped cohort of younger ESRD patients.

Bottom Line: Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels.Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

View Article: PubMed Central - PubMed

Affiliation: Department of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT

Introduction: Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho.

Methods and material: In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively.

Results: fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness.

Discussion: The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

No MeSH data available.


Related in: MedlinePlus