Overexpression of CTRP9 attenuates the development of atherosclerosis in apolipoprotein E-deficient mice

Huang, Chengmin; Zhang, Peng; Li, Tingting; Li, Jun; Liu, Tianjiao; Zuo, Anju; Chen, Jiying; Guo, Yuan

doi:10.1007/s11010-018-3473-y

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…In this study, our results suggest that CTRP9 may be closely related to the development and progression of CAP. However, numerous studies have demonstrated the protective role of CTRP9 in atherosclerosis and its associated ischemic cardiomyopathy, which seems to be inconsistent with our conclusions (Huang et al, 2019; Li et al, 2019; Zhang et al, 2019;). One possible explanation is that CTRP9 is increased by feedback in hypertension and atherosclerosis to counter pathologic factors, similar to BNP, which has a diuretic and vasodilatory effect and is increased in patients with chronic heart failure.…”

Section: Discussioncontrasting

confidence: 99%

C1q/TNF‐related protein‐9 is elevated in hypertension and associated with the occurrence of hypertension‐related atherogenesis

Zhou

Cheng

Wang

et al. 2021

Cell Biology International

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C1q‐tumor necrosis factor‐related protein‐9 (CTRP9) is an important adipocytokine that is closely associated with cardiovascular disease. This study aimed to detect CTRP9 expression in hypertensive patients and mice and to analyze its effects on hypertension‐related atherogenesis. First, circulating CTRP9 levels were detected in both nonhypertensive subjects and hypertensive patients. The results showed that plasma CTRP9 levels were increased in hypertension patients compared with control subjects and gradually elevated in the Grade I, Grade II, and Grade III groups. While nondipper state did not affect CTRP9 expression in hypertension patients. Hypertension patients with carotid atherosclerotic plaque (CAP) exhibited higher CTRP9 levels and the high CTRP9 group exhibited significantly higher CAP morbidity, CTRP9 levels were positively correlated with the occurrence of CAP. Then, effects of CTRP9 on angiotensin II (Ang II)‐induced endothelial dysfunction were analyzed in vitro, and the results exhibited that treatment with Ang II significantly increased CTRP9 mRNA expression in endothelial cells (ECs), and downregulation of CTRP9 expression aggravated Ang II‐induced endothelial dysfunction in ECs. Mice were infused with Ang II, and CTRP9 was also increased in Ang II‐infused mice and mainly secreted by ECs. In Ang II‐infused ApoE−/− mice, treatment with recombinant CTRP9 significantly reduced atherosclerotic area and alleviated endothelial dysfunction. In conclusion, our results may found that CTRP9 delayed the progression of hypertension‐related arteriosclerosis by alleviating endothelial dysfunction.

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Section: Discussioncontrasting

confidence: 99%

C1q/TNF‐related protein‐9 is elevated in hypertension and associated with the occurrence of hypertension‐related atherogenesis

Zhou

Cheng

Wang

et al. 2021

Cell Biology International

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“…Furthermore, elevated levels of CTRP9 improved the vascular plaque stability and alleviated the development of atherosclerosis in ApoE knockout mice by decreasing pro-in ammatory cytokines in macrophages [29,30]. The current ndings are consistent with previous results [27][28][29][30] in terms of the protective effects of CTRP9 in the pathogenesis of atherosclerosis.…”

Section: Discussionsupporting

confidence: 91%

“…CTRP9 has been suggested to act as regulator of vascular function, with bene cial effects on atherosclerosis and CVD [10,26]. In several previous animal studies, CTRP9 contributed to an advantageous vascular effect, especially concerning atherosclerosis [27][28][29][30]. CTRP9 was demonstrated to mediate endothelium-dependent vasorelaxation [27] and suppress vascular smooth muscle cell proliferation and neointimal formation [28].…”

Section: Discussionmentioning

confidence: 99%

“…CTRP9 has attracted a lot of attention since it was discovered in 2009 [31]. Accumulating evidence has indicated the protective effects of CTRP9 against atherosclerosis through multiple mechanisms including inhibition of the in ammatory response [11,29,30,32,33] and amelioration of endothelial dysfunction [10,32,34]. The ndings implicate the CTRP9 adipokine as a promising target to prevent and treat atherosclerosis-associated disease.…”

Section: Discussionmentioning

confidence: 99%

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C1q/TNF-related protein-9 attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy

Lee

Yoo

Kim

et al. 2021

Molecular and Cellular Endocrinology

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Background: Autophagy is an important process in the pathogenesis of atherosclerosis. C1q/tumor necrosis factor-related protein 9 (CTRP9) is the closest adiponectin paralog. CTRP9 has purported antiaging and anti-atherogenic effects, but its roles in autophagy and endothelial senescence are unknown.The aim of this study was to evaluate whether CTRP9 prevents palmitic acid (PA)-induced endothelial senescence by promoting autophagy.Methods: After no treatment or pre-treatment of human umbilical vein endothelial cells with CTRP9 prior to PA treatment, the level of senescence was measured by senescence associated acidic β-galactosidase staining and the level of hyperphosphorylated pRB protein. Autophagy was evaluated by LC3 conversion and the level of p62/SQSTM1, a protein degraded during autophagy. Autophagosome-lysosome fusion was detected by uorescence microscopy.Results: Pre-treatment with CTRP9 attenuated PA-induced endothelial senescence. CTRP9 increased the conversion of LC3-I to LC3-II, and decreased the level of p62 in time-and dose-dependent manners.Although both CTRP9 and PA treatment increased the LC3 conversion, treatment of PA increased p62 and decreased the fusion of autophagosomes and lysosomes, which represented decreased autophagic ux. However, pre-treatment with CTRP9 recovered the autophagic ux inhibited by PA. AMP-activated kinase (AMPK) activation was involved in LC3 conversion and decreased p62 induced by CTRP9.Conclusion: CTRP9 inhibits PA-induced endothelial senescence by recovering autophagy and autophagic ux through AMPK activation.

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“…We have demonstrated that administration of CTRP9 attenuates the neointimal hyperplasia in response to vascular injury in wild-type (WT) mice (Uemura et al, 2013). Overexpression of CTRP9 also reduced atherosclerotic lesion formation in apolipoprotein E knockout mice fed a high-fat diet (Huang et al, 2019). We and others have shown that systemic delivery of CTRP9 attenuates myocardial infarct size in WT or diabetic mice after ischemia-reperfusion injury (IRI) (Kambara et al, 2012;Su et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF-Related Protein 9 Promotes Revascularization in Response to Ischemia via an eNOS-Dependent Manner

et al. 2020

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Strategies to promote revascularization are valuable for ischemic cardiovascular disease. Although C1q/TNF-related protein (CTRP) 9 is an adiponectin paralog with protective properties against cardiometabolic disorders, the role of endogenous CTRP9 in endothelial function is largely unknown. This study aimed to investigate the effects of CTRP9 on revascularization processes and dissected the potential mechanisms. CTRP9knockout (KO) and wild-type (WT) mice were subjected to unilateral hindlimb ischemic surgery. CTRP9-KO mice exhibited impaired blood flow recovery and decreased capillary density in the ischemic limb compared with WT mice. In both CTRP9-KO and WT mice, systemic delivery of an adenoviral vector expressing CTRP9 (Ad-CTRP9) accelerated blood flow recovery. Treatment with recombinant CTRP9 protein increased network formation and migration of cultured human umbilical vein endothelial cells (HUVECs). CTRP9 promoted the phosphorylation of AMP-activated kinase (AMPK), Akt, and endothelial nitric oxide synthase (eNOS) in HUVECs. CTRP9-KO mice also showed reduced phosphorylation levels of AMPK, Akt, and eNOS in the ischemic limbs compared with WT mice. Furthermore, blockade of AMPK or Akt signaling pathway reversed the CTRP9-stimulated eNOS phosphorylation in HUVECs. Treatment with the NOS inhibitor significantly reduced CTRP9-stimulated network formation and migration of HUVECs. Of note, Ad-CTRP9 had no effects on blood flow of the ischemic limb in eNOS-KO mice. These results indicated that CTRP9 promotes endothelial cell function and ischemia-induced revascularization through the eNOS-dependent mechanism, suggesting that CTRP9 represents a target molecule for treatment of ischemic vascular diseases.

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Overexpression of CTRP9 attenuates the development of atherosclerosis in apolipoprotein E-deficient mice

Cited by 20 publications

References 43 publications

C1q/TNF‐related protein‐9 is elevated in hypertension and associated with the occurrence of hypertension‐related atherogenesis

C1q/TNF‐related protein‐9 is elevated in hypertension and associated with the occurrence of hypertension‐related atherogenesis

C1q/TNF-related protein-9 attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy

C1q/TNF-Related Protein 9 Promotes Revascularization in Response to Ischemia via an eNOS-Dependent Manner

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