The Role of CCR5 in Macrophage Infiltration and Loss of the Anticontractile Effect of Perivascular Adipose Tissue during Systemic Arterial Hypertension

Abstract

Hypertension is a global health condition with significant impacts on morbidity and mortality, often associated with functional and structural changes in perivascular adipose tissue (PVAT). This tissue plays a crucial role in modulating vascular function by regulating vascular tone and contractile response. During hypertension, the renin-angiotensin system, particularly angiotensin II (ANG-II), is closely linked to oxidative stress and inflammation. Under normal conditions, PVAT exerts an anti-contractile effect, attenuating the response to vasoconstrictor agents. However, under pathophysiological conditions such as hypertension, PVAT can become dysfunctional, characterized by the excessive production of inflammatory cytokines and reactive oxygen species (ROS), as well as immune cell infiltration. These events compromise the anti-contractile function of PVAT and contribute to the deterioration of vascular function. Signaling mediated by the AT1 receptor and the production of CCL5 have been implicated in PVAT dysfunction and macrophage polarization, both of which are critical factors in the inflammation and vascular dysfunction associated with hypertension. This study will investigate the hypothesis that CCR5 plays a crucial role in PVAT dysfunction in hypertension by promoting the recruitment and polarization of macrophages toward the M1 phenotype. This polarization is associated with increased production of ROS and pro-inflammatory cytokines, which compromise the anti-contractile function of PVAT and exacerbate vascular dysfunction. Additionally, we will explore the potential role of the AT1 receptor in modulating this dysfunction, examining how its activation may influence the inflammatory response and PVAT function. The expected outcomes of this study may provide a deeper understanding of the molecular and cellular mechanisms involved in inflammation and cardiovascular risk associated with hypertension, as well as offer new perspectives for the development of therapeutic strategies aimed at improving PVAT function and managing arterial hypertension.