Arterial hypertension is a persistent global health issue increasingly identified as a low-grade chronic inflammatory condition (Fisher and Curfman, 2018). This condition is characterized by elevated levels of pro-inflammatory cytokines in the vascular system and circulation (Patrick et al., 2021; Harrison and Patrick, 2024; Guzik et al., 2024). Vascular inflammation is closely associated with changes in vascular tone and remodeling (Lin and Davis, 2023). Numerous experimental and clinical studies have shown that both innate and adaptive immune responses play pivotal roles in the pathophysiology of cardiovascular diseases, including arterial hypertension (Harrison et al., 2010). Particularly, T and B lymphocytes within the adaptive immune system are significant contributors to angiotensin II and deoxycorticosterone-induced arterial hypertension (Guzik et al., 2007). However, the role of the innate immune system in the initiation and progression of arterial hypertension remains under-explored and warrants further investigation.

The innate immune response serves as the body's primary defense against pathogens, identifying these agents through pattern recognition receptors (PRRs) like toll-like receptors (TLRs) (Takeuchi and Akira, 2010). Previously, it has been noted that spontaneously hypertensive rats (SHR) display an overexpression of TLR4 in resistance arteries compared to Wistar rats. Additionally, chronic inhibition of TLR4 through an anti-TLR4 antibody has been shown to reduce blood pressure and reverse vascular hypercontractility via a cyclooxygenase-dependent mechanism (Bomfim et al., 2012, 2015).

TLR9 has emerged as an important receptor for recognizing mitochondrial DNA released during trauma, apoptosis, or cell necrosis (Latz et al., 2004). TLR9 is expressed not only in immune cells but also in non-immune cells, including endothelial cells, fibroblasts, adipocytes, and cardiomyocytes (Erridge et al., 2008; Garrafa et al., 2011; Marques and Boneca, 2011). Upon activation, TLR9 moves from the endoplasmic reticulum to the endosome and lysosomal compartments, triggering the MyD88 signaling pathway, which leads to the production of pro-inflammatory cytokines (Akira and Hoshino, 2003; Vollmer, 2006). TLR9 is a key player in the pathogenesis of cardiovascular diseases such as atherosclerosis, preeclampsia, and arterial hypertension by promoting inflammation and vascular dysfunction (Erridge et al., 2008; Goulopoulou et al., 2012; Harwani et al., 2012; McCarthy et al., 2015). For instance, during myocardial infarction, the release of large amounts of mitochondrial DNA activates TLR9, initiating an inflammatory response in cardiac tissue and resulting in elevated blood pressure levels (Zhang et al., 2010).

Perivascular adipose tissue (PVAT), a layer of fat surrounding blood vessels, plays a crucial role in regulating vascular tone. PVAT acts as a paracrine modulator, releasing substances that influence vessel contraction and relaxation, such as adipokines, cytokines, and vasodilatory factors (Soltis and Cassis, 1991; Costa et al., 2018; Victorio et al., 2020). Under normal conditions, PVAT exerts a protective effect on the cardiovascular system, aiding in the maintenance of vascular homeostasis and blood pressure regulation. However, in diseases like obesity and hypertension, PVAT can become dysfunctional and inflamed (Fernández-Alfonso et al., 2013; Ayala-Lopez and Watts, 2017). Excessive fat accumulation induces a pro-inflammatory state, characterized by the release of inflammatory cytokines like TNF-α and IL-6 and a decrease in the production of anti-inflammatory agents such as adiponectin and nitric oxide (NO). This inflammatory milieu contributes to endothelial dysfunction, insulin resistance, oxidative stress, and vessel stiffening, exacerbating arterial hypertension and increasing cardiovascular risk (Nosalski and Guzik, 2017; Adachi et al., 2022).

Given the presence of systemic and tissue inflammation in arterial hypertension, the expression of TLR9 receptors in non-immune cells fostering pro-inflammatory cytokine production, and the promotion of redox imbalance by inflammation, this study hypothesizes that in arterial hypertension, there is activation of TLR9 receptors, production of pro-inflammatory cytokines, oxidative stress in PVAT, and consequent dysfunction of this tissue.