Activation of the Innate Immune System in Atherosclerotic Disease

Abstract

Innate immunity is the first line of defence against invading micro-organisms. The family of Toll-like receptors (TLRs) recognizes pathogen-associated molecular patterns (PAMPs) that are carried by the invading micro-organisms. Infectious pathogens have been implicated to play an important role in atherosclerosis. Nowadays, evidence is accumulating that TLRs play an important role in the initiation and progression of atherosclerosis too. A lot is known about the exogenous ligands that are able to activate the TLRs, but it is also known that endogenous ligands have the capacity to activate TLRs when exogenous ligands are absent. Studies on knockout mice, epidemiological studies and even human polymorphism studies confirmed the important role of TLRs in development and progression of atherosclerotic disease. Studies with antagonists against TLR ligands and vaccination studies demonstrated that TLR signaling might be a potential target for intervention in the initiation and progression of atherosclerosis.

Endogenous Inflammatory Molecules Engage Toll-Like Receptors in Cardiovascular Disease

“…Previous epidemiological studies have proved that exogenous bacterial ligands can induce an inflammatory response in the arterial wall and initiate atherosclerosis [8] , and therefore, a link between atherosclerosis and TLRs has been established. Experimental data have shown that lipopolysaccharide (LPS) and peptidoglycan (PGN), both potent TLR activators, can accelerate plaque formation in atherosclerotic mice [6] . These results point to a potential role of TLR-2 and TLR-4 in the pathogenesis of atherosclerotic disease.…”

“…Fundamental cells of the innate immune system, namely monocytes and macrophages, are present within atherosclerotic lesions and express various pattern-recognition receptors, among which, Toll-like receptors (TLRs). TLRs occur in atherosclerotic lesions [5] where they are triggered by both exogenous (bacterial and viral pathogens) and endogenous (tissue damage-associated) molecules [6] . Several endogenous ligands for TLRs are expressed during inflammation in atherosclerotic plaques or ischemic heart where they might play a role in disease pathogenesis and progression.…”

SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease

“…The American Heart Association suggested that the blood C-reactive protein (CRP) level is a risk factor in coronary disease development [9]. In addition, the immune capacity in the human body plays a critical role in the induction and deterioration of atherosclerosis, with monocytes/macrophages playing critical roles in this action [10]. Monocyte participation in the progression of atherosclerotic plaques was demonstrated in the 1970s, with monocyte aggregation manifested in atherosclerotic lesions [11].…”

7 Monocyte subpopulations in patients following st-elevation myocardial infarction: implications for post-infarction left ventricular remodelling and clinical outcomes

“…The innate immune system plays a major role in the initiation and propagation of atherosclerosis, with monocytes/macrophages being the key players in this process (Oude Nijhuis et al, 2007).…”