Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto's thyroiditis

Area of Science:

• Endocrinology
• Cardiovascular Research
• Inflammation Biology

Background:

• Subclinical hypothyroidism (sHT) is associated with peripheral endothelial dysfunction and chronic low-grade inflammation.
• Understanding the interplay between inflammation and endothelial function in sHT is crucial for identifying therapeutic targets.

Purpose of the Study:

• To investigate the role of low-grade systemic inflammation in the pathogenesis of endothelial dysfunction in patients with sHT and autoimmune thyroiditis.
• To elucidate the specific inflammatory pathways involved in endothelial dysfunction in sHT.

Main Methods:

• Forearm blood flow response to acetylcholine was measured in sHT patients and healthy controls.
• Vascular function was assessed with and without local blockade of cyclooxygenase (COX) or nitric oxide synthase (NOS), and with antioxidant administration.
• The effects of systemic COX inhibition (indomethacin) and selective COX-2 blockade (celecoxib) were evaluated.

Main Results:

• sHT patients exhibited higher C-reactive protein and IL-6 levels, indicating increased inflammation.
• Endothelial dysfunction in sHT was characterized by impaired vasodilation to acetylcholine, which was resistant to NOS blockade but improved with vitamin C.
• Systemic, but not local, indomethacin or celecoxib normalized vasodilation in sHT patients, suggesting a COX-2-dependent mechanism.

Conclusions:

• Low-grade chronic inflammation in sHT patients contributes to endothelial dysfunction.
• This dysfunction involves impaired nitric oxide availability mediated by a COX-2-dependent pathway.
• The process leads to increased oxidative stress, highlighting a potential therapeutic target for managing endothelial dysfunction in sHT.