Hypothyroidism and pulmonary arterial hypertension

Ghamra, Ziad; Dweik, Raed A.; Arroliga, Alejandro C.

doi:10.1016/j.amjmed.2003.09.040

Cited by 5 publications

(1 citation statement)

References 6 publications

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“…The patients with PAH had low fT3 levels and high miRNA-21 levels. These results support previous studies that showed that PAH is associated with hypothyroidism [55] and that PAH patients have higher circulating miRNA-21 levels than SSc patients without PAH [56]. These publications strengthen the reliability of our results and the link between the levels of the pro-fibrotic miRNA-21, and T3, and suggest that a larger group of PAH patients should be further investigated to better understand the relationship between miRNA-21, D3, and T3.…”

Section: Discussionsupporting

confidence: 92%

αvβ3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis

Kohon

Levy

Hornik-Lurie

et al. 2023

IJMS

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Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Key players mediating fibrosis are myofibroblasts (MF) that, following transforming growth factor β (TGFβ) exposure, produce a collagen-rich extracellular matrix (ECM) that induces myofibroblast differentiation. Myofibroblasts express αvβ3 integrin (a membrane receptor for thyroid hormones) and miRNA-21 that promotes deiodinase-type-3 expression (D3), causing the degradation of triiodothyronine (T3) that attenuates fibrosis. We hypothesized that αvβ3 affects the fibrotic processes through its thyroid hormones (THs) binding site. To test this, dermal fibroblasts (DF) were cultured with/without TGFβ and removed with a base, leaving only normal/fibrotic ECMs in wells. Then, DF were cultured on the ECMs with/without tetrac (αvβ3 ligand, T4 antagonist), and evaluated for pro-fibrotic characteristics, αvβ3, miRNA-21, and D3 levels. Blood free-T3 (fT3), miRNA-21 levels, and the modified Rodnan skin score (MRSS) were evaluated in SSc patients. We found that the “fibrotic-ECM” significantly increased the pro-fibrotic characteristics of DF and the levels of miRNA-21, D3, and αvβ3, compared to the “normal-ECM.” Tetrac significantly inhibited the effects of the “fibrotic-ECM” on the cells. In accordance with tetrac’s effect on D3/miRNA-21, a negative correlation was found between the patients’ fT3 to miRNA-21 levels, and to the development of pulmonary arterial hypertension (PAH). We conclude that occupying the THs binding site of αvβ3 may delay the development of fibrosis.

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Section: Discussionsupporting

confidence: 92%