Purinergic Signaling in Controlling Macrophage and T Cell Functions During Atherosclerosis Development

Abstract

Atherosclerosis is a hardening and narrowing of arteries causing a reduction of blood flow. It is a leading cause of death in industrialized countries as it causes heart attacks, strokes, and peripheral vascular disease. Pathogenesis of the atherosclerotic lesion (atheroma) relies on the accumulation of cholesterol-containing low-density lipoproteins (LDL) and on changes of artery endothelium that becomes adhesive for monocytes and lymphocytes. Immunomediated inflammatory response stimulated by lipoprotein oxidation, cytokine secretion and release of pro-inflammatory mediators, worsens the pathological context by amplifying tissue damage to the arterial lining and increasing flow-limiting stenosis. Formation of thrombi upon rupture of the endothelium and the fibrous cup may also occur, triggering thrombosis often threatening the patient’s life. Purinergic signaling, i.e., cell responses induced by stimulation of P2 and P1 membrane receptors for the extracellular nucleotides (ATP, ADP, UTP, and UDP) and nucleosides (adenosine), has been implicated in modulating the immunological response in atherosclerotic cardiovascular disease. In this review we will describe advancements in the understanding of purinergic modulation of the two main immune cells involved in atherogenesis, i.e., monocytes/macrophages and T lymphocytes, highlighting modulation of pro- and anti-atherosclerotic mediated responses of purinergic signaling in these cells and providing new insights to point out their potential clinical significance.

Doppler Ultrasound Study on the Effects of Different Blood Uric Acid Levels on the Carotid Artery Intima-media Thickness in Patients with Gout

“…Age and LDL-C increasing the risk of atherosclerosis has been confirmed by many studies [23,25], and the results of this study also confirmed this. In addition, the results of this study showed that the course of gout increased the risk of CCAIMT thickening, which was inconsistent with the results of the study by Mariano Andrés [16].…”

“…In addition, the results of this study showed that LY% was a protective factor for CCAIMT, and LY% could reduce the risk of CCAIMT thickening. Studies have shown that macrophages and LY % play a key role in the development of atherosclerosis and can provide signals for the potential pro-inflammatory background of atherosclerosis [23]. The results of this study were inconsistent with the aforementioned pathological process.…”

TDP43 Exacerbates Atherosclerosis Progression by Promoting Inflammation and Lipid Uptake of Macrophages

“…response and lipid uptake tightly connects with atherosclerotic progression (Ferrari et al, 2020). Specifically blocking these undesirable functions in macrophages may be an attractive choice for alleviating AS and its complications.…”

“…Cardiovascular disease is still the leading cause of death all over the world, and AS is one of the major etiologies ( Kuznetsova et al, 2020 ). Macrophage-mediated inflammatory response and lipid uptake tightly connects with atherosclerotic progression ( Ferrari et al, 2020 ). Specifically blocking these undesirable functions in macrophages may be an attractive choice for alleviating AS and its complications.…”

The Adenosine Pathway and Human Immunodeficiency Virus-Associated Inflammation

“…NLRP3 inflammasome activation and IL-1β production are factors that contribute to HIV-associated inflammation, and these are strongly implicated in the development of atherosclerosis and hypertension [ 78 , 79 ]. Activation of the NLRP3 inflammasome and release of IL-1β are strongly tied to purinergic signaling, particularly P2X 7 R stimulation [ 78 , 80 ]. In addition, the inflammasome system may contribute to the loss of CD4 + T-cell populations and overall lack of immune recovery seen in PWH [ 81 ].…”