C1q/<scp>TNF</scp>‐related protein 9 inhibits the cholesterol‐induced Vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP‐dependent kinase

Liu, Qi; Zhang, Hui; Lin, Jianzhong; Zhang, Ruoxi; Chen, Shuyuan; Liu, Wei; Sun, Meng; Du, Wenjuan; Hou, Jingbo; Yu, Bo

doi:10.1111/jcmm.13196

Cited by 35 publications

(34 citation statements)

References 50 publications

(58 reference statements)

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“…CTRP9 has been suggested to act as a regulator of vascular function, and to exert protective effects in ischemic diseases (12). The cytoprotective effects of CTRP9 have been well documented, through promoting cell proliferation, inhibiting the oxidative response, and modulating endoplasmic reticulum stress (13,33). The present study demonstrated that CTRP9 treatment promoted MSC proliferation and viability and increased their immunoregulatory and angiogenic abilities, accompanied by elongation of telomere length and recovery of telomerase activity.…”

Section: Discussionsupporting

confidence: 57%

CTRP9 ameliorates cellular senescence via PGC‑1α/AMPK signaling in mesenchymal stem cells

Zhu

Wang

et al. 2018

Int J Mol Med

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Stroke is the second most common cause of death worldwide, and thus, it imposes great financial burdens on both individuals and society. Mesenchymal stem cell (MSC) therapy is a promising approach for ischemic brain injury. However, MSC treatment potential is progressively reduced with age, limiting their therapeutic efficacy for brain repair post‑stroke. C1q and tumor necrosis factor‑related protein 9 (CTRP9) is a novel cytoprotective cytokine with antioxidant effects, which is highly expressed in brain tissue. The present study tested the hypothesis that CTRP9 might act as an antisenescence factor to promote the rejuvenation of aged MSCs. MSCs were isolated from the bone marrow of young (8‑weeks‑old) and aged (18‑months‑old) male C57BL/6 mice. Cell proliferation was measured by Cell Counting Kit‑8 assay and cell viability was determined by MTT assay. Gene expression levels of interleukin (IL)‑6 and IL‑10 were evaluated with reverse transcription‑quantitative polymerase chain reaction, and secretion of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and insulin‑like growth factor were measured by ELISA. The expression levels of proteins in the peroxisome proliferator‑activated receptor γcoactivator (PGC)‑1α/AMP‑activated protein kinase (AMPK) signaling pathway were investigated with western blotting. Oxidative stress was evaluated by detecting mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity and malondialdehyde. MSCs isolated from aged mice exhibited reduced proliferation and viability, and impaired immunoregulatory and paracrine abilities, compared with MSCs from younger mice. CTRP9 had a significant antisenescence effect in aged MSCs by activating PGC‑1α/AMPK signaling and decreasing the oxidative response. Silencing either PGC‑1α or AMPK abolished the above effects of CTRP9. These results suggest that CTRP9 may have a critical role in cellular senescence by facilitating stem cell rejuvenation, and may therefore have the potential to enhance the efficacy of stem cell therapy.

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Section: Discussionsupporting

confidence: 57%

CTRP9 ameliorates cellular senescence via PGC‑1α/AMPK signaling in mesenchymal stem cells

Zhu

Wang

et al. 2018

Int J Mol Med

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“…Simultaneously, we consider that cardiac CTRP9 expression might be regulated by PPAR-γ (Su et al, 2013), and CTRP9 prevents activation of the TLR4-MyD88-p65 pathway by activating AMPK to inhibit the cholesterol-induced vascular smooth muscle cell (VSMC) phenotype switch (Q. Liu et al, 2017). Conversely, we have known that the signaling molecules TLR4, AMPK, NF-κB, and PPAR-γ, which are associated with CTRP9, are involved in macrophage polarization.…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF‐related protein‐9 promotes macrophage polarization and improves cardiac dysfunction after myocardial infarction

Liu

Yin

et al. 2019

Journal Cellular Physiology

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The timely regulation of inflammatory M1 macrophage polarization toward regenerative M2 macrophages suggests the possibility of immunotherapy after myocardial infarction (MI). C1q/TNF‐related protein‐9 (CTRP9) has anti‐inflammatory effects and can ameliorate heart function in mice after long‐term myocardial infarction. The role of CTRP9 in macrophage polarization remains completely unclear. This study determined whether CTRP9 can preserve post‐MI early cardiac function through the regulation of macrophage polarization. In the present study, an adenovirus‐delivered CTRP9 supplement promoted macrophage polarization at Day 3 post MI and improved cardiac function at Day 7 post MI. Pretreatment with gCTRP9 promoted the M1 to M2 polarization transition and attenuated inflammation after lipopolysaccharide + interferon‐γ stimulation; the effects were partly abrogated by the adenosine monophosphate kinase (AMPK) inhibitor compound C and were obviously reinforced by pyrrolidine dithiocarbamate, a nuclear factor‐κB (NF‐κB) inhibitor. Meanwhile, CTPR9 markedly reduced the expression of toll‐like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF‐κB p65 phosphorylation by promoting AMPK phosphorylation in vivo and in vitro. Moreover, the competitive binding of gCTRP9 and LPS to the myeloid differentiation protein 2 (MD2)/TLR4 complex was associated with direct binding to MD2, thereby inhibiting the downstream signaling molecule MyD88. Taken together, we demonstrated that CTRP9 improved post‐MI early cardiac function, at least in part, by modulating M1/M2 macrophage polarization, largely via the TLR4/MD2/MyD88 and AMPK‐NF‐κB pathways.

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“…Nevertheless, CTRP9 could inhibit NF‐κB activation and reduce expression of adhesion molecules (Jung et al, ). Finally, CTRP9 could protect the blood vessels through inhibiting cholesterol uptake in vascular smooth muscle cells (Liu, Zhang et al, ) and promoting cholesterol efflux to reduce the formation of foam cell in virtue of inducing autophagy in an AMPK/mTOR signaling pathway‐dependent manner (Zhang, Liu et al, ), particularly in that the high cholesterol level has been considered as a risk factor for vascular remodeling at present.…”

Section: Introductionmentioning

confidence: 99%

“…Besides, another research showed that CTRP9 could reduce the levels of inflammatory cytokines in coronary atherosclerotic plaques in ApoE knockout mice, thereby increasing atherosclerotic plaque stability (Zhang et al, ). In addition, CTRP9 may enhance atherosclerotic plaque stability via inhibiting the phenotypic switch of vascular smooth muscle cells which are closely related to atherosclerotic plaque stability (Liu, Zhang et al, ).…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF‐related protein 9: A novel therapeutic target in ischemic stroke?

Yang

Fan

Sawmiller

et al. 2018

J of Neuroscience Research

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| INTRODUC TI ONIschemic stroke and coronary atherosclerosis disease (CAD) are both kinds of atherosclerotic diseases with high morbidity and high mortality, which have already been on the spotlight in both clinic and research. Vascular lesion is the major feature in the pathogenesis of these two diseases. Initially, the endothelial cells (EC) are damaged by risk factors, followed with activated platelets, inflammatory reactions, and accelerated vessel wall remodeling. Consequently, atherosclerotic plaques forming, rupture and erosion, with different subtypes of surface thrombosis, vasospasm and distal vascular embolization, lead to ischemic lesions, including ischemic stroke and CAD. However, the molecular mechanism of vascular lesion is complicated, which requires further research for the full understanding of pathogenesis of atherosclerotic diseases.C1q/TNF-related protein 9 (CTRP9) is a newly discovered adipokine. By searching databases of Medline and Web of Science (WOS), we found only a few reports about this factor, most of which were published in the past two years. Meanwhile, they mainly expounded the role of CTRP9 in the blood vessels related pathogenesis of CAD, including regulating energy metabolism, modulating vasomotion, protecting EC, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting heart. Here, we reviewed the genic features, proteinic features and physiologic functions of CTRP9, and proposed some possible associations between CTRP9 and ischemic stroke as well. AbstractIschemic stroke has become a serious public health problem, which is in need of advanced research on the prevention and treatment. As a newly discovered adipokine, C1q/TNF-related protein 9 (CTRP9) plays a vital role in the pathogenesis of coronary atherosclerosis disease (CAD), including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting heart. The present review raised a critical question of whether CTRP9 could also have the capacity of protecting the brain tissue and decreasing the severity of brain lesions in the ischemic stroke since CAD and ischemic stroke are both the major subtypes of atherosclerotic vascular diseases which share a large of common pathogenesis in the vascular lesion particularly. Therefore, we proposed that CTRP9 could be a feasible biomarker and potential therapeutic target in ischemic stroke on the basis of the reviewed research reports. K E Y W O R D Sadipokine, coronary atherosclerosis disease, CTRP9, ischemic stroke | 129 YANG et al.

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C1q/TNF‐related protein 9 inhibits the cholesterol‐induced Vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP‐dependent kinase

Cited by 35 publications

References 50 publications

CTRP9 ameliorates cellular senescence via PGC‑1α/AMPK signaling in mesenchymal stem cells

CTRP9 ameliorates cellular senescence via PGC‑1α/AMPK signaling in mesenchymal stem cells

C1q/TNF‐related protein‐9 promotes macrophage polarization and improves cardiac dysfunction after myocardial infarction

C1q/TNF‐related protein 9: A novel therapeutic target in ischemic stroke?

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