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.

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

Ferrari Davide
Primo
;
Milani Daniela;Celeghini Claudio;Casciano Fabio
Ultimo
2021

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.
2021
Ferrari, Davide; la Sala, Andrea; Milani, Daniela; Celeghini, Claudio; Casciano, Fabio
File in questo prodotto:
File Dimensione Formato  
Ferrari 2020_proof.pdf

accesso aperto

Descrizione: Proof di stampa
Tipologia: Post-print
Licenza: Creative commons
Dimensione 2.29 MB
Formato Adobe PDF
2.29 MB Adobe PDF Visualizza/Apri
fimmu-11-617804.pdf

accesso aperto

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: Creative commons
Dimensione 3.11 MB
Formato Adobe PDF
3.11 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2438858
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 11
social impact