Evaluation of the phenotype and the anticontractile effect of aortic PVAT in rats with hypothyroidism

• Grant number: 25/13334-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciana Venturini Rossoni
• Grantee: Luciana Venturini Rossoni
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/03813-4 - The role of mineralocorticoid receptor on perivascular adipose tissue dysfunction in renovascular hypertension., AP.R

Abstract

Triiodothyronine (T3), the active form of thyroid hormone (TH), plays a crucial role in regulating metabolism and maintaining energy homeostasis. Its metabolic action occurs primarily through interaction with nuclear receptors (TR¿1, TR¿2, TR¿1, and TR¿2), by which T3 regulates gene expression and function in various tissues such as adipose tissue (AT), heart, and blood vessels. Hypothyroidism, characterized by T3 deficiency, induces a hypometabolic state, with decreased energy expenditure, impaired lipolysis, and accumulation of adipose tissue, resulting in a higher risk of dyslipidemias, such as elevated cholesterol levels, and cardiovascular diseases -given that the heart and blood vessels are targets of this hormone. In the heart, there is a reduction in the expression of ion channels in nodal cells (HCN2 and HCN4) and ¿-adrenergic receptors, resulting in decreased heart rate, myocardial mechanics, and consequently, reduced cardiac output. At the same time, vascular resistance increases due to decreased nitric oxide bioavailability and reduced expression/activity of ion channels, which impair endothelium-induced vasodilation and favor vasoconstriction. However, vascular dysfunction in hypothyroidism appears to depend on the degree and duration of T3 deficiency, potentially affecting both the endothelium and vascular smooth muscle. T3 is also well known to influence adipose tissue differentiation and adipocyte metabolic activity, modulating thermogenesis through the stimulation of UCP-1 expression, and influencing the phenotypes of white adipose tissue (WAT) and brown adipose tissue (BAT)]. However, when analyzing the vasculature, there are no studies evaluating how reduced T3 availability affects the function of perivascular adipose tissue (PVAT). PVAT is a type of adipose tissue with unique characteristics, located around blood vessels, and it plays a crucial role in regulating vascular function and structure through the secretion of adipokines, inflammatory factors, and hormones. Dysfunction of PVAT is involved in the pathophysiology of cardiovascular diseases. Preliminary data from our group identified the expression of T3 nuclear receptors (TR¿1, TR¿2, TR¿1, and TR¿2) in thoracic aorta PVAT (tPVAT) of healthy rats, suggesting that this tissue may respond directly to the action of THs. Thus, considering the importance of T3 in vascular and peripheral adipose tissue physiology, and the key role of PVAT in vascular homeostasis, the present project hypothesizes that T3 deficiency will impair the anticontractile action of tPVAT, associated with tissue whitening and a pro-inflammatory effect. (AU)