Human protein S inhibits the uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human macrophages

Liao, Dan; Wang, Xinwen; Li, Min; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

doi:10.1182/blood-2008-05-158048

Cited by 35 publications

(33 citation statements)

References 36 publications

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“…PS and Gas6 may provide a possible recognition bridge between phagocytes and apoptotic cells, acting as socalled "binding molecules" (22). PS could bind and induce the phosphorylation of the Mer receptor tyrosine kinase in tissue macrophages (29), and a Northern blot analysis showed almost exclusive expression of Mer in the murine monocytic cell lineage (14). Therefore, the infiltrating monocytes and/or macrophages may be the cell source of the increased Mer expression in the TG heart.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse myocardium with cardio-specific TNF-α overexpression

Higuchi

Kubota

Koyanagi

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Heart failure (HF) has been recognized as a hypercoagulable state. However, the natural anticoagulation systems in the failing heart have not been studied. Recent experimental and clinical data have indicated that not only the thrombomodulin (TM)/protein C (PC) pathway but also the protein S (PS)/tissue factor pathway inhibitor (TFPI) system function as potent natural anticoagulants. To investigate the balance between procoagulant and anticoagulant activities in the failing heart, we measured the cardiac expression of tissue factor (TF), type 1 plasminogen activator inhibitor (PAI-1), TM, PC, PS, and TFPI by RT-PCR and/or Western blot analysis in male transgenic (TG) mice with heart-specific overexpression of TNF-α. Both procoagulant (TF and PAI-1) and anticoagulant (PS and TFPI) factors were upregulated in the myocardium of 24-wk-old TG (end-stage HF) but not in that of 4-wk-old TG (early decompensated HF) compared with the wild-type mice. Both factors were also upregulated in the infarcted myocardium at 3 days after coronary ligation in the wild-type mice. The expression of TM was downregulated in the TG heart, and PC was not detected in the hearts. The transcript levels of PS orphan receptors, Mer and Tyro3, but not Axl, were significantly upregulated in the TG heart. Double immunohistochemical staining revealed that myocardial infiltrating CD3-positive T cells may produce PS in the TG myocardium. In conclusion, the PS/TFPI was upregulated in the myocardium of a different etiological model of HF, thus suggesting a role for the PS/TFPI system in the protection of the failing heart under both inflammatory and hypercoagulable states.

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Section: Discussionmentioning

confidence: 99%

Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse myocardium with cardio-specific TNF-α overexpression

Higuchi

Kubota

Koyanagi

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…on May 10, 2018. by guest www.bloodjournal.org From low-density lipoprotein uptake in macrophages, thereby reducing the formation of foam cells. 58 These mechanisms can possibly explain part of the recent findings that SNP mutations in TAM receptor genes are correlated with the formation of atherosclerotic plaques. 59,60 Protein S is upregulated by interleukin-4 (IL-4) in primary T cells.…”

Section: Tam Receptorsmentioning

confidence: 97%

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

Meer

Poll

Veer

2014

Blood

275

228

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TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K–dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S+/−, Gas6−/−, TAM−/−, and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.

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“…Recent studies have showed that activation of p38 mitogen-activated protein kinase (MAPK) [18], PI3K-Akt [19][20][21] and Mer receptor tyrosine kinase [22] increases SR-A transcription. Lowbush blueberries [23], ginkgo biloba extract (EGb761) [24], and human protein S [22] targeting these signals can inhibit SR-A expression. The endogenous regulators for SR-A expression are not fully elucidated, and whether SR-A expression is regulated by paracrine/ autocrine factors is particularly not known.…”

Section: Introductionmentioning

confidence: 99%

Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice

Dai

Cai

Mao

et al. 2012

Journal of Molecular and Cellular Cardiology

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Human protein S inhibits the uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human macrophages

Cited by 35 publications

References 36 publications

Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse myocardium with cardio-specific TNF-α overexpression

Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse myocardium with cardio-specific TNF-α overexpression

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice

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