Role of Toll like receptor signaling pathway in ischemic coronary artery disease

Abstract

Inflammatory process plays a fundamental role in ischemic coronary artery disease (CAD) in terms of both the etiology of atherosclerosis and the pathophysiology of CAD. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. It is therefore important to clarify the mechanism underlying the activation of the immune response in the pathogenesis of CAD. Currently 10 toll-like receptors (TLRs) have been reported in mammalian species, and these appear to recognize distinct pathogen-associated molecular patterns controlling innate immune responses. In recent studies, signaling of two forms of human TLR (TLR2 and TLR4) has been shown to be involved in the pathogenesis of CAD, establishing a key link between the progression of coronary atherosclerosis and immune response to both foreign pathogens and endogenously generated inflammatory ligands. A better understanding of TLR signal may provide a novel therapeutic agent for the treatment of CAD. This review summarizes the relationship between the pathogenesis of ischemic coronary artery disease and the human TLR system.

Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer

“…The D299G SNP is implicated in gastric cancer, athero-182 sclerosis, sepsis, and asthma, and a G11481C mutation has been linked to prostate cancer (El-Omar et al, 2008). A number of studies also suggest a possible role for TLR4 in cardiovascular disease (Frantz et al, 2007;Satoh et al, 2008), inflammatory bowel disease (Fukata and Abreu, 2007), Alzheimer's disease (Balistreri et al, 2008), rheumatoid arthritis (van den Berg et al, 2007), renal disease (Anders et al, 2004), obesity, and diabetes types I and II (Kim, 2006); whether the genetic evidence will support the disease tissue and model observations remains to be proven. In mouse models, for example, inhibition of TLR4 is beneficial in mouse models of rheumatoid arthritis (Eder et al, 2004), and patients with the disease carrying the D299G mutation have altered macrophage responses to LPS (Roelofs et al, 2008), but a clear genetic link between TLR4 and rheumatoid arthritis has yet to be found.…”

“…Atherosclerosis models have been studied extensively with TLR2, and TLR4 is possibly associated with lesion development in mice (Tobias and Curtiss, 2008); much evidence supports a role for both TLR2 and TLR4 in atherosclerosis and ischemic coronary artery disease in humans (Satoh et al, 2008). Asthma and atopy have been linked to TLR2, and a promoter polymorphism TLR2 (Ϫ16,934 A/T) in children of European farmers was associated with a lower risk of developing these diseases (Eder et al, 2004).…”

A novel method to quantify gene set functional association based on gene ontology

“…Of the 10 pathways seven (which are marked with superscript 'a' in the table), reportedly play important roles in CHD. Additionally, the remaining three pathways (which are marked with superscript 'b'), have recently been associated with CHD [43,[45][46][47][49][50][51]. For example, the sigma-1 receptor causes the pathway for neuroactive ligand-receptor interaction to malfunction, leading to memory process and cognitive disorders [42].…”

Toll-Like Receptors in Angiogenesis

“…Furthermore, the detection of several TLR members in multiple tissues and cell typesbesides cells of the immune system -led to a more wide-ranging view on TLRs. Inflammatory disorders such as atherosclerosis [8] and liver disease [9], but also autoimmune diseases [10], are critically influenced by TLRs especially. Moreover, an involvement of TLRs in allograft acceptance/rejection during transplantation [11] or contact allergy to nickel [12] has been shown.…”