Inflammasome, T Lymphocytes and Innate-Adaptive Immunity Crosstalk: Role in Cardiovascular Disease and Therapeutic Perspectives

Abstract

Over the past few decades, lot of evidences have shown atherosclerosis as a chronic progressive disease with an exquisite inflammatory feature. More recently, the role of innate immune response in the onset and progression of coronary artery disease (CAD) and an adaptive immunity imbalance, mostly involving T cell sub-sets, have been documented. Therefore, like in many other inflammatory and autoimmune disorders, an altered innate-adaptive immunity crosstalk could represent the key of the inflammatory burden leading to atherosclerotic plaque formation and progression and to the breakdown of plaque stability. In this review, we will address the role of inflammasome in innate immunity and in the imbalance of adaptive immunity. We will discuss how this altered immune crosstalk is related to CAD onset and progression. We will also discuss how unravelling the key molecular mechanisms is of paramount importance in the development of therapeutic tools to delay the chronic progression and prevent the acute destabilization of atherosclerotic plaque.

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture

“…The pathophysiology of ACS is strictly related to an outburst of inflammatory (Biasucci et al, 2017) and immune-mediated response (Crea and Liuzzo, 2013), taking over the concept of the atheroma as a mere lipid-driven lesion (Soehnlein and Libby, 2021). Differences in innate and adaptive immune system have been described in ACS patients (Liuzzo et al, 2007(Liuzzo et al, , 2020Flego et al, 2016;Leers et al, 2017;Pedicino et al, 2018a;Leistner et al, 2020). Starting from PBMCs as source material, our group documented an altered hyaluronan metabolism in NSTE-ACS patients presenting with plaque erosion (Pedicino et al, 2018b), further confirmed by later investigations on platelets and monocyte-platelet interaction (Vinci et al, 2021).…”

Changes in the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios before and after percutaneous coronary intervention and their impact on the prognosis of patients with acute coronary syndrome

“…Inflammation plays an important role in the occurrence and development of atherosclerotic cardiovascular disease and is related to the poor prognosis of ACS ( 5 , 6 , 22 ). NLR and PLR are inflammatory indicators that have been used to assess the levels of inflammation in cardiovascular diseases in recent years ( 15 , 18 ).…”

Inflammation in coronary artery disease: Which biomarker and which treatment?

“…In addition, it has been shown that the tryptophan metabolite 3-hydroxyanthranilic acid has immune regulatory properties that can be used to decrease atherosclerosis in mice by regulating T-cell-dependent inflammation and lowering plasma lipids. 12 Second, which patients might benefit from an antiinflammatory treatment? Although a large body of evidence suggests that CRP is a good biomarker for the identification of patients with residual inflammatory risk and blood cell count, as suggested by the study of Zhao et al, 5 there might be another interesting biomarker of risk in this setting: T-cell perturbation seems to identify patients with ACS at high risk of major coronary events even better than high-sensitivity CRP.…”

“…In addition, it has been shown that the tryptophan metabolite 3-hydroxyanthranilic acid has immune regulatory properties that can be used to decrease atherosclerosis in mice by regulating T-cell-dependent inflammation and lowering plasma lipids. 12…”