Endogenous Inflammatory Molecules Engage Toll-Like Receptors in Cardiovascular Disease

Abstract

Innate immunity is important in the pathogenesis and progression of cardiovascular disease. Innate immune cells express various pattern-recognition receptors, among which also Toll-like receptors (TLRs). TLRs occur in atherosclerotic lesions where they are triggered by both exogenous (bacterial and viral pathogens) and endogenous (tissue damage-associated) molecules. Several endogenous TLR activators are described in relation to atherosclerotic disease or ischemia-induced cardiac injury. Experimental animal models have proved the role of TLR endogenous activators in disease initiation and further development. Nowadays, researchers aim to unravel the exact mechanisms involved in the endogenous ligand-dependent TLR signaling and to discover new potential activators, released during pathological conditions such as atherosclerosis and related ischemic manifestations. This review provides an overview of the currently known endogenous molecules which trigger innate immunity via TLRs in cardiovascular disease.

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

“…In complex, these literature data suggest that the TLR-4 pathway should seem to have a crucial role in sporadic TAA patho-physiology and represent a crucial link between pathways linked to sporadic TAA development and immune system, as suggested in our reports [33,50,[52][53][54][55]. However, this encouraging and increasing evidence is fruit prevalently of animal investigations.…”

“…As above mentioned, it has been suggested that TLR-4 pathway has a key role in the pathophysiology of several CVDs [50,[52][53][54][55]. Recently, the group of Pasterkamp has provided an overview of the endogenous molecules, released under cellular cardiovascular stress and damage, the DAMPs, which can trigger innate immunity via TLR-4-mediated signaling pathway and induce CVD onset as consequence [52].…”

“…Recently, the group of Pasterkamp has provided an overview of the endogenous molecules, released under cellular cardiovascular stress and damage, the DAMPs, which can trigger innate immunity via TLR-4-mediated signaling pathway and induce CVD onset as consequence [52]. In addition, polymorphisms of TLR-4 gene (MIM: 603030), and particularly the rs4986790 TLR-4 polymorphism, have been associated with the risk of several CVDs and other age-related diseases, even if contrasting results have been reported in literature [33,50,[52][53][54][55].…”

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…The model is centered on an innate immunity receptor signaling pathway of [9], the Toll-like receptor-4(TLR-4) signaling pathway, which has the role of a hub. TLR-4 is recognized to have a key function in the host defence against Gram-negative bacteria, viruses, fungi and mycoplasma [10], but also in the patho-physiology of several age-related diseases [9,11], including CVDs, as stressed in our studies [4,8,11,12] and described by other groups [13][14][15]. Recently, its role has emerged in maintaining aortic homeostasis, but also in establishing aorta aneurysm [4,8,[16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Developmental Onset of Bilirubin-induced Neurotoxicity Involves Toll-like Receptor 2-dependent Signaling in Humanized UDP-glucuronosyltransferase1 Mice

“…HSPs are predominantly intracellular molecules and are rapidly released following cell death (28). Recently, HSPs were implicated in modulating immune responses by interaction with TLRs as damage-associated molecular patterns (29,30). The association of HSP27 with cell injury and innate immunity prompted us to examine the role of TLR in response to bilirubin toxicity during neonatal brain development.…”