Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction

Abstract

Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and other mediators, which may enter the circulation in soluble form. These primary cytokines also induce production of the messenger cytokine interleukin-6, which stimulates the liver to increase production of acute-phase reactants such as C-reactive protein. In addition, platelets and adipose tissue can generate inflammatory mediators relevant to atherothrombosis. Despite the irreplaceable utility of plasma lipid profiles in assessment of atherosclerotic risk, these profiles provide an incomplete picture. Indeed, many cardiovascular events occur in individuals with plasma cholesterol concentrations below the National Cholesterol Education Program thresholds of 200 mg/dL for total cholesterol and 130 mg/dL for low-density lipoprotein (LDL) cholesterol. The concept of the involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. C-reactive protein is currently the best validated inflammatory biomarker; in addition, soluble CD40 ligand, adiponectin, interleukin 18, and matrix metalloproteinase 9 may provide additional information for cardiovascular risk stratification and prediction. This review retraces the biology of atherothrombosis and the evidence supporting the role of inflammatory biomarkers in predicting primary cardiovascular events in this biologic context.

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

“…We selected several proinflammatory molecules considered to be representative inflammatory mediators involved in atherogenesis to test this hypothesis 8, 9, 10. Of these selected mediators, we observed that IL‐1 β expression was significantly higher in clots from patients with large artery atherosclerosis than in those with either cardioembolism or undetermined etiology.…”

“…Large artery atherosclerosis is an important etiology of acute ischemic stroke and inflammation is well‐known to play a pivotal role in all stages of atherosclerosis, from lesion initiation to progression and destabilization 8. The pathogenesis of atherosclerosis is crucially influenced by inflammatory mediators such as proinflammatory cytokines and extracellular proteases secreted by smooth muscle cells, endothelial cells, and immune cells 8, 9, 10.…”

The associations of interleukin-6 (IL-6) and downstream inflammatory markers with risk of cardiovascular disease: The Caerphilly Study

“…There is increasing evidence that inflammation plays an important role in atherosclerosis and its clinical complications: cardiovascular disease (CVD) including coronary heart disease (CHD) and ischaemic stroke [1]. Previous reports from the prospective Caerphilly Study have shown that circulating inflammatory markers including fibrinogen, plasma viscosity and leucocyte count [2,3]; C-reactive protein (CRP) [4]; and ␣1-antitrypsin and ␣2-macroglobulin [5] are associated with CHD risk.…”

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

“…A large body of evidence also indicates a central role for inflammation in atherosclerotic disease [14,15]. Multiple epidemiological studies have associated C-reactive protein (CRP), an acute-phase reactant and marker of inflammation, with CVD risk [16].…”