Salusin-β contributes to vascular remodeling associated with hypertension via promoting vascular smooth muscle cell proliferation and vascular fibrosis

Sun, Hai-Jian; Liu, Tongyan; Zhang, Feng; Xiong, Xiao-Qing; Wang, Juejin; Qi, Chunjian; Li, Yuehua; Kang, Yu-Ming; Zhou, Ye-Bo; Han, Ying; Gao, Xing-Ya; Zhu, Guo‐Qing

doi:10.1016/j.bbadis.2015.05.008

Cited by 65 publications

(65 citation statements)

References 49 publications

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“…3). The peptide that opposes salusin-α, salusin-β, promotes the migration and proliferation of VSMCs and is involved in vascular remodeling [19,20,26]. VSMC proliferation in the development of atherosclerosis is most likely initiated and regulated by growth factors such as PDGF-BB.…”

Section: Discussionmentioning

confidence: 99%

“…Atherosclerosis development is accelerated by salusin-β via increased acyl-coenzyme A:cholesterol acyltransferase-1 expression in human monocyte-derived macrophages, whereas salusin-α may have the opposite effect: serum salusin-α levels are inversely correlated with the maximum intima-media thickness in patients with coronary artery disease [15,16]. Although there is a link between salusin-α and atherosclerosis [11,16,17], it is unclear whether salusin-α plays a role in the proliferation and migration of SMCs, another important cellular event in atherosclerotic lesion formation, even though some reports have shown that salusin-β promotes SMC migration and proliferation and vascular inflammation and fibrosis [18][19][20]. In this study, we attempted to examine the effects of salusin-α on rabbit atherosclerosis, with emphasis on the role of the peptide in SMCs and the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Gao

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. Methods: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. Results: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. Conclusion: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Gao

Zhang

et al. 2018

Cell Physiol Biochem

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“…The infusion rate was selected on the basis of previous study that this dose induces a slowly progressive hypertension in which the Ang II effects of appetite suppression and depressed body weight gain are avoided [28]. Blood pressure of tail artery was measured weekly in a conscious state with a noninvasive computerized tail-cuff system (NIBP, AD Instruments, Sydney, Australia), and blood pressure of carotid artery was measured with an direct intubation method under anesthesia as we previously reported [29]. Mice were sacrificed using 4% isoflurane in air and subsequent exsanguination or decapitation.…”

Section: Methodsmentioning

confidence: 99%

“…The DNA synthesis of VSMCs was measured using a Cell-Light TM EdU Apollo®567. The EdU positive cells were counted and normalized by the total number of Hoechst 33342 stained cells [29]. In addition, expression of proliferating cell nuclear antigen (PCNA) was measured with Western blotting and used as an marker of proliferation in aortic media of mice [37, 38].…”

Section: Methodsmentioning

confidence: 99%

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

Ren

Tong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Angiotensin (Ang) II plays vital roles in vascular inflammation and remodeling in hypertension. Phenotypic transformation of vascular smooth muscle cells (VSMCs) is a major initiating factor for vascular remodeling. The present study was designed to determine the roles of NLRP3 inflammasome activation in Ang II-induced VSMC phenotypic transformation and vascular remodeling in hypertension. Methods: Primary VSMCs from the aorta of NLRP3 knockout (NLRP3^-/-) mice and wild-type (WT) mice were treated with Ang II for 24 h. Subcutaneous infusion of Ang II via osmotic minipump for 2 weeks was used to induce vascular remodeling and hypertension in WT and NLRP3^-/- mice. Results: NLRP3 gene deletion attenuates Ang II-induced NLRP3 inflammasome activation, phenotypic transformation from a contractile phenotype to a synthetic phenotype and proliferation in primary mice VSMCs. Ang II-induced hypertension and vascular remodeling in WT mice were attenuated in NLRP3^-/- mice. Furthermore, Ang II-induced NLRP3 inflammasome activation, phenotypic transformation and proliferating cell nuclear antigen (PCNA) upregulation were inhibited in the media of aorta of NLRP3^-/- mice. Conclusions: NLRP3 inflammasome activation contributes to Ang II-induced VSMC phenotypic transformation and proliferation as well as vascular remodeling and hypertension.

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“…The absorbance was measured at 450 nm using a microplate reader (SYNERGY H4, BioTek, VT, USA). EdU incorporation was also applied to determine the DNA synthesis of HUVECs using In Vitro Imaging Kit (Guangzhou RiboBio, Guangzhou, China) [52,53]. The collected HUVECs were harvested and fixed in ice-cold 70% ethanol overnight at −20 °C.…”

Section: Methodsmentioning

confidence: 99%

C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

Sun

Zhu

Zhou

et al. 2017

IJMS

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Oxidized low-density lipoprotein (ox-LDL) accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9) is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO) production and oxidative stress in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS) production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL), as well as endothelial nitric oxide synthase (eNOS). Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α) and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation.

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Salusin-β contributes to vascular remodeling associated with hypertension via promoting vascular smooth muscle cell proliferation and vascular fibrosis

Cited by 65 publications

References 49 publications

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

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