The why and how of adaptive immune responses in ischemic cardiovascular disease

Abstract

yslipidemia and elevated low-density lipoprotein (LDL) cholesterol levels are causally involved in the chronic inflammatory response of the vascular wall 1 . LDL oxidation in the intima and the sterile vascular inflammation associated with it engage adaptive immune responses that profoundly modulate atherosclerosis, from lesion initiation and progression to the occurrence of clinical events 2 (Box 1). Accumulating evidence also implicates adaptive immunity in the response to ischemic heart injury 3 as a modulator of both post-ischemic cardiac remodeling and atherosclerosis progression 4 .Recent studies have provided proof of concept that targeting inflammation may limit the occurrence of cardiovascular (CV) events 5,6 . Here, we consider the intimate and complex interactions of the immune system with the heart and the vasculature in health and atherosclerotic disease, with a particular focus on adaptive immune mechanisms and their selective manipulation for patient benefit.

Pleiotropic genetic architecture and novel loci for C-reactive protein levels

“…Metabolic and immune are evolutionarily conserved and functionally entangled systems whose interplay is believed to play a central role in the pathophysiology of a wide spectrum of cardiovascular diseases 1 . As a result, metabolic disturbances are commonly associated with immune responses in relation to cardiovascular outcomes.…”

Adverse Cardiac Effects of CAR T-Cell Therapy: Characteristics, Surveillance, Management, and Future Research Directions

“…24 Other developing cardiovascular immune therapies include engineered CAR Treg cells directed against atherosclerosisrelevant epitopes to suppress local inflammation and developing tolerogenic Treg-based vaccines to prevent and treat cardiovascular diseases. 56 Overall this highlights how an improved understanding of T-cell biology in cardiovascular disease can be leveraged for both better management of cardiovascular adverse events and to expand CAR T-cell use for directed immunotherapy of cardiovascular diseases.…”

Macrophage mediators and mechanisms in cardiovascular disease

“…192 However, broad interventions in the immune system might impair host immunity against infections and cancer and not all immune interventions yielded successful results in CVD. 193,194 Low-dose methotrexate (LDM), an established therapy in patients with inflammatory diseases including Crohn's disease and rheumatoid arthritis, did not alter serum levels of IL-1, IL-6, and hsCRP and cardiovascular events in patients with stable atherosclerosis in comparison to placebo controls. 195 It is tempting to speculate that the recently uncovered macrophage subsets might differ between patients in composition and functionality and thus contribute to the moderate success of some of these therapies.…”