Abstract
BackgroundThe association between dilated cardiomyopathy (DCM) and low thyroid hormone (TH) levels has been previously described. In these patients abnormal thyroid function is significantly related to impaired left ventricular (LV) function and increased risk of death. Although TH was originally thought to be produced exclusively by the thyroid gland, we recently reported TH biosynthesis in the human ischemic heart.ObjectivesBased on these findings, we evaluated whether the genes required for TH production are also altered in patients with DCM.MethodsTwenty-three LV tissue samples were obtained from patients with DCM (n = 13) undergoing heart transplantation and control donors (n = 10), and used for RNA sequencing analysis. The number of LV DCM samples was increased to 23 to determine total T4 and T3 tissue levels by ELISA.ResultsWe found that all components of TH biosynthesis are expressed in human dilated heart tissue. Expression of genes encoding thyroperoxidase (–2.57-fold, P < 0.05) and dual oxidase 2 (2.64-fold, P < 0.01), the main enzymatic system of TH production, was significantly altered in patients with DCM and significantly associated with LV remodeling parameters. Thyroxine (T4) cardiac tissue levels were significantly increased (P < 0.01), whilst triiodothyronine (T3) levels were significantly diminished (P < 0.05) in the patients.ConclusionsExpression of TH biosynthesis machinery in the heart and total tissue levels of T4 and T3, are altered in patients with DCM. Given the relevance of TH in cardiac pathology, our results provide a basis for new gene-based therapeutic strategies for treating DCM.
Highlights
We found that all components of thyroid hormone (TH) biosynthesis are expressed in human dilated heart tissue
Given the relevance of TH in cardiac pathology, our results provide a basis for new gene-based therapeutic strategies for treating dilated cardiomyopathy (DCM)
Dilated cardiomyopathy (DCM) is characterized by cardiac chambers dilation and ventricular dysfunction that frequently results in heart failure (HF), a condition that is associated with a high mortality rate [1]
Summary
Dilated cardiomyopathy (DCM) is characterized by cardiac chambers dilation and ventricular dysfunction that frequently results in heart failure (HF), a condition that is associated with a high mortality rate [1]. The association between DCM and low thyroid hormone (TH) levels has been described [2,3,4]. H2O2 produced by DUOX is used by TPO to oxidize iodide and iodinate tyrosyl residues of thyroglobulin (TG), forming iodinated tyrosyl intermediates. TPO couples these intermediates to form the hormones T3 and T4, which are endocytosed, hydrolyzed, and secreted into the blood [13,14]. The association between dilated cardiomyopathy (DCM) and low thyroid hormone (TH) levels has been previously described. In these patients abnormal thyroid function is significantly related to impaired left ventricular (LV) function and increased risk of death. TH was originally thought to be produced exclusively by the thyroid gland, we recently reported TH biosynthesis in the human ischemic heart
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
