I BNS regulates interleukin-6 production and inhibits neointimal formation after vascular injury in mice

Niida, Tomiharu; Isoda, Kikuo; Kitagaki, Manabu; Ishigami, Norio; Adachi, Takeshi; Matsubara, Osamu; Takeda, Kiyoshi; Kishimoto, Tadamitsu; Ohsuzu, Fumitaka

doi:10.1093/cvr/cvr323

Cited by 19 publications

(16 citation statements)

References 35 publications

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“…These cytokines include tumor necrosis factor-α, interferon-γ, and interleukin-6, etc. 37–40 Since STAT3 is a central regulator in vascular responses to the inflammatory cytokines, 41 and JAK3 can regulate STAT3 activation, it is likely that JAK3 also mediate the function of these cytokines in vascular remodeling, which can be studied in the future.…”

Section: Discussionmentioning

confidence: 99%

Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling

Wang

Cui

Chuang

et al. 2017

ATVB

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Objective Vascular remodeling due to smooth muscle cell (SMC) proliferation is a common process occurring in a number of vascular diseases such as atherosclerosis, aortic aneurysm, post-transplant vasculopathy, and restenosis after angioplasty, etc. The molecular mechanism underlying SMC proliferation, however, is not completed understood. The objective of this study is to determine the role and mechanism of Janus kinase 3 (JAK3) in vascular remodeling and SMC proliferation. Approach and Results Platelet-derived growth factor (PDGF)-BB, a SMC mitogen, induces JAK3 expression and phosphorylation while stimulating SMC proliferation. Janex-1, a specific inhibitor of JAK3, or knockdown of JAK3 by shRNA, inhibits the SMC proliferation. Conversely, ectopic expression of JAK3 promotes SMC proliferation. Mechanistically, JAK3 promotes the phosphorylation of signal transducer and activator of transcription 3 and c-Jun N-terminal kinase in SMC, two signaling pathways known to be critical for SMC proliferation and vascular remodeling. Blockade of these two signaling pathways by their inhibitors impeded the JAK3-mediated SMC proliferation. In vivo, knockdown of JAK3 attenuates injury-induced neointima formation with attenuated neointimal SMC proliferation. Knockdown of JAK3 also induces neointimal SMC apoptosis in rat carotid artery balloon-injury model. Conclusion Our results demonstrate that JAK3 mediates SMC proliferation and survival during injury-induced vascular remodeling, which provides a potential therapeutic target for preventing neointimal hyperplasia in proliferative vascular diseases.

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Section: Discussionmentioning

confidence: 99%

Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling

Wang

Cui

Chuang

et al. 2017

ATVB

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“…IL-6 effects on vascular system are mediated via NF- κ B signaling, which plays a key role in vascular remodeling. Inhibition of NF- κ B via deletion of I κ BNS, a nuclear I κ B regulatory protein of NF- κ B, reduces intimal hyperplasia after vascular injury in mice via NF- κ B-mediated IL-6 production [41]. …”

Section: Inflammation and Cardiovascular Diseasementioning

confidence: 99%

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

Pacurari

Kafoury

Tchounwou

et al. 2014

International Journal of Inflammation

299

230

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The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

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“…It has been well established that during the repair of vascular injury, multiple cytokines and growth factors are released that stimulate vascular cell proliferation (5–7). For example, following angioplasty, the upregulated production of platelet-derived growth factor (PDGF) initiates proliferation-related signaling pathways to stimulate VSMC proliferation in response to vascular injury (8,9).…”

Section: Introductionmentioning

confidence: 99%

Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway

Gan

Wang

et al. 2013

Experimental and Therapeutic Medicine

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An imbalance in the proliferation and migration of vascular smooth muscle cells (VSMCs) is significant in the onset and progression of vascular diseases, including arteriosclerosis and restenosis subsequent to vein grafting or coronary intervention. Rosuvastatin, a selective inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, has pharmacological properties including the ability to reduce low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) levels, slow atherosclerosis progression and improve coronary heart disease outcomes. However, little is known concerning the molecular mechanism by which rosuvastatin affects vascular cell dynamics. In this study, we studied the inhibitory role of rosuvastatin on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, as well as the molecular mechanisms involved. MTT data showed that rosuvastatin markedly inhibited the proliferation of PDGF-BB-induced VSMCs in a time-dependent manner. VSMCs are able to dedifferentiate into a proliferative phenotype in response to PDGF-BB stimulation; however, rosuvastatin effectively attenuated this phenotype switching. Moreover, we also showed that rosuvastatin significantly suppressed PDGF-BB-induced VSMC migration, which may be a result of its inhibitory effect on the protein expression of matrix metalloproteinase-2 (MMP2) and MMP9. Investigation into the molecular mechanisms involved revealed that rosuvastatin inhibited the mitogen-activated protein kinase (MAPK) signaling pathway by downregulating extracellular signal-regulated kinase (ERK) and p38 MAPK, although the phosphorylation level of c-Jun N-terminal kinase (c-JNK) was not altered following rosuvastatin treatment. In conclusion, the present study showed that rosuvastatin suppressed PDGF-BB-induced VSMC proliferation and migration, indicating that rosuvastatin has the potential to become a promising therapeutic agent for the treatment of atherosclerosis and restenosis.

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I BNS regulates interleukin-6 production and inhibits neointimal formation after vascular injury in mice

Abstract: IκBNS down-regulates TLR4 expression, NF-κB activity, and IL-6 production after vascular injury. IκBNS might suppress intimal hyperplasia caused by vascular inflammation such as atherosclerosis, and restenosis after angioplasty.

Cited by 19 publications

References 35 publications

Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling

Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway

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