Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism

Ahmad, Abrar; Sundquist, Kristina; Zöller, Bengt; Svensson, Peter; Sundquist, Jan; Memon, Ashfaque A.

doi:10.1007/s11239-017-1491-3

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…Furthermore, sex differences associated with TLR9 and TLR8 polymorphisms have also been described in CVDs. In whole blood of aging patients with venous thromboembolism, it was observed an association between the TLR9 rs5743836 polymorphism and the risk of venous thromboembolism recurrence in aged women; however, this association was not observed in aged men ( Ahmad et al, 2017 ). Moreover, in whole blood of aging patients with ischemic stroke, it was observed that the TLR8 rs3764880 polymorphism is associated with the susceptibility to ischemic stroke in aging men.…”

Section: Toll-like Receptors Sex Differences and Cardiovascular Agingmentioning

confidence: 94%

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

Echem

Akamine

2021

Front. Aging

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Human life span expectancy has increased, and aging affects the organism in several ways, leading, for example, to an increased risk of cardiovascular diseases. Age-adjusted prevalence of the cardiovascular diseases is higher in males than females. Aging also affects the gonadal sex hormones and the sex differences observed in cardiovascular diseases may be therefore impacted. Hormonal changes associated with aging may also affect the immune system and the immune response is sexually different. The immune system plays a role in the pathogenesis of cardiovascular diseases. In this context, toll-like receptors (TLRs) are a family of pattern recognition receptors of the immune system whose activation induces the synthesis of pro-inflammatory molecules. They are expressed throughout the cardiovascular system and their activation has been widely described in cardiovascular diseases. Some recent evidence demonstrates that there are sex differences associated with TLR responses and that these receptors may be affected by sex hormones and their receptors, suggesting that TLRs may contribute to the sex differences observed in cardiovascular diseases. Recent evidence also shows that sex differences of TLRs in cardiovascular system persists with aging, which may represent a new paradigm about the mechanisms that contribute to the sex differences in cardiovascular aging. Therefore, in this mini review we describe the latest findings regarding the sex differences of TLRs and associated signaling in cardiovascular diseases during aging.

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Section: Toll-like Receptors Sex Differences and Cardiovascular Agingmentioning

confidence: 94%

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

Echem

Akamine

2021

Front. Aging

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“…NET-related extracellular DNA is recognized by the toll-like receptor 9 (TLR9) on both monocytes and PMNs [ 99 , 100 ], and a mutation in this receptor has been linked to VTE in patients [ 101 , 102 ]. TLR9 −/− mouse VT models have demonstrated larger VT, decreased collagen and fibrin deposition, and an increase in PMNs at 2 days and Mo/MΦ cells after 1 week [ 103 ].…”

Section: Neutrophils and Early Thrombogenesismentioning

confidence: 99%

Immune cell–mediated venous thrombus resolution

Henke,

Nicklas,

Obi

2023

Research and Practice in Thrombosis and Haemostasis

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“…NET-related extracellular DNA is recognized by the toll-like receptor 9 (TLR9) on both monocytes and PMNs, [72,73] and a mutation in this receptor has been linked to VTE in human patients [74,75]. TLR9 -/mouse VT models have demonstrated a consistent pattern of enlarged thrombus, reductions in collagen and fibrin deposition, and a dramatic increase in PMNs at 2 days and Mo/MΦ cells after 1 week [76].…”

Section: Neutrophils and The Potential Regulation Of Early Structuralmentioning

confidence: 99%

Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms

Nicklas

Gordon

Henke

2020

IJMS

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Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy. already progressed past the point of anticoagulant efficacy [12,13]. Thus, there is potential clinical utility in investigating and controlling the process by which DVTs resolve in order to provide better care to these later-stage patients, with less bleeding risk. Overview of Venous Thrombus Development in HumansThe time sequence of DVT development and resolution was correctly suggested as early as 1962, based on empirical stains that detected changes in the nanoscopic roughness of clotted material [14]. As Lendrum et. al. remarked, "we consider that the intracytoplasmic granules, which we think are engulfed fibrin, seen in pulmonary phagocytes and in the endothelium of arteries and veins containing thrombus, are better shown by this (methyl-scarlet-blue) method than by any of the others." In fresh clot (whether in deep veins or in diabetic kidneys), platelets and erythrocytes are initially linked in a fine mesh yielding a relatively smooth surface (stage 1). A mat of the medium-textured fibrin replaces the initial thrombus (stage 2), which is gradually replaced by much coarser collagen (stage 3). This staging of clot development quickly became the basis of a pathological guide to grade thrombi [15]. The current three-stage refinement of the DVT grading scheme indicates that the turnover of erythrocyte-rich to fibrin-rich clot in humans is complete approximately seven days after the initial thrombotic event [16], whereas fibrin deposition commences after one day [17]. Various leukocytes, initially neutrophils and later macrophages, are believed to control this progression of DVTs development from a mass of erythrocytes, to fibrin, and finally to collagen [18]. Infiltrating T-lymphocytes and macrophages conta...

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Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism

Cited by 6 publications

References 45 publications

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

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

Immune cell–mediated venous thrombus resolution

Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms

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