Biomarkers of endothelial dysfunction and cytokine levels in hypothyroidism: a series of meta-analyses.

BACKGROUND

Hypothyroidism (HT) is associated with different comorbidities comprising increased arterial stiffness and decreased flow-mediated dilatation. The exact pathological mechanism of endothelial activation and dysfunction (ED) in HT remains unknown. We conducted a systematic review and meta-analyses to provide an overview of the pathogenesis of ED in HT.

METHODS

The literature search was done in February 2024 for studies analyzing traditional and novel circulating biomarkers of ED in patients with HT, including cytokines and chemokines. Random-effect models were used except when no heterogeneity was found. Protocol was registered under the number PROSPERO CRD42024540560.

RESULTS

25 macromolecules and 66 studies were entered into analyses. HT was associated with increased levels of E-selectin, soluble intercellular adhesion molecule-1, osteoprotegerin, and oxidized-LDL (p < 0.02). Results were not conclusive for endothelin-1. Interleukin (IL)-6, IL-12 and CXCL10 were higher in HT (p < 0.05). Subjects with overt HT may display a proinflammatory tendency with increased levels of IL-6 and interferon-γ, and decreased levels of TGF-β (p < 0.05).

CONCLUSIONS

The data presented and discussed here highlights the association between HT and soluble biomarkers of ED. Inflammatory mediators released by activated T-cells and macrophages may aggravate local and systemic inflammation, which arouses more inflammation, forming a vicious circle leading to ED.