Attenuated Recovery of Contractile Function in Aging Hearts Following Global Ischemia/Reperfusion: Role of Extracellular HSP27 and TLR4

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

“…One novel role for TLR4 is to regulate autophagy within the heart in a process mediated by the Histone Deacetylase - HDAC1 [ 124 ]. Furthermore, TLR4 signaling plays an important role in promoting inflammation following ischemia/reperfusion injury in the aging heart [ 125 ]. These studies suggest that evaluating the role of TLR4 signaling within the heart of old COVID-19 patients may provide prognostic capacities to predict cardiovascular disease outcomes in these patients.…”

Toll-like receptor 4 and the inflammation during aging

“…The central role of TLR4 in adipose tissue inflammation during the aging process was confirmed by the study conducted by He and colleagues 48 . Additionally, there are several reports regarding the inflammatory roles of TLR4 in age-related disorders in the animal models 2,49,50 . Therefore, it seems that the animal models directed us to consider TLR4 as an important receptor involved in the pathogenesis of inflammation in the elderly population.…”

“…Campbell and colleagues reported a TLR4-dependent increasing in platelet granzyme A, a serine protease that regulates monocyte-induced inflammatory gene synthesis and promotes inflammasome activation 51 . Altogether, upregulation and TLR4 overexpression and its corresponding intracellular signaling pathways can be a risk factor for the induction or stimulation of inflammation in the elderly population and the subsequent induction of aging complications 2,49,50 . Figure 1 provides up-to-date information confirming the role of TLR4 and its associated intracellular signaling pathways in the pathogenesis of age-related complications.…”

Toll-Like Receptors Represent an Important Link for Sex Differences in Cardiovascular Aging and Diseases

“…Aortic smooth muscle cells from aged female mice showed higher TLR4 protein and mRNA expression compared to young female mice ( Song et al, 2012 ). Furthermore, TLR2 and TLR4 protein expression, pro-inflammatory molecules and some DAMPs were higher in aged than in young male mice ( Karuppagounder et al, 2016 ; Ao et al, 2017 ). In another study, it was observed that although aged male mice hearts did not show a higher TLR4 protein expression compared to young male mice, the TLR4 knockout improved aging-associated cardiac changes, suggesting that this receptor is a possible therapeutic target in aging ( Wang et al, 2018 ).…”