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vaspin alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence

Emergency and Critical Care Medicine 2024年第1期4卷 4-15页

作者： Haiying Rui Huaxiang Yu Dan Zou Kai Chi Ping Xu Xiaoshuai Song Lulu Liu Xuting Wu Jinxin Wang Li Xue Department of Emergency Medicine and Chest Pain Center Qilu Hospital of Shandong UniversityJinanShandongChina Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityQilu Hospital of Shandong UniversityJinanShandongChina Key Laboratory of Emergency and Critical Care Medicine of Shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinanShandongChina The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese Ministry of Health and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineQilu Hospital of Shandong UniversityJinanShandongChina.

Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin *** studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and ***,it remains unclear whether vaspin exerts specific effects on pathological cardiac ***:An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol(ISO)in C57BL/6 and vaspin-ko *** was administered intraperitoneally to mice,for further study.H9c2 cells and neonatal rat ventricular myocytes(NRVMs)were treated with ISO to induce *** vaspin fusion protein,the proteasome inhibitor MG132,and chloroquine diphosphate were used for further mechanistic ***:Here,we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy,fibrosis,and cardiomyocyte senescence in mice treated with ***,the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and ***,vaspin significantly potentiated the ISO-induced decrease in *** rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro,respectively,and participated in vaspin-mediated ***,the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and *** data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination ***:Our results show,for the first time,that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence,providing potential preventive and therapeutic targets for pathological cardiac hyper

关键词： Autophagic flux Myocardial senescence Pathological cardiac hypertrophy Ubiquitination vaspin

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Serum omentin and vaspin levels in cirrhotic patients with and without portal vein thrombosis

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World Journal of Gastroenterology 2017年第14期23卷 2613-2624页

作者： Michal Kukla Marek Waluga Michal Zorniak Agnieszka Berdowska Piotr Wosiewicz Tomasz Sawczyn Rafal J Buldak Marek Ochman Katarzyna Ziora Tadeusz Krzemiński Marek Hartleb Department of Gastroenterology and Hepatology Medical University of Silesia in Katowice Department of Microbiology and Biotechnology Jan Dlugosz University Department of Physiology Medical University of Silesia in Katowice Department of Biochemistry in Zabrze Medical University of Silesia in Katowice Department of Cardiac Surgery and Transplantation Silesian Center for Heart Diseases Department of Pediatrics Medical University of Silesia in Katowice Department of Pharmacology Medical University of Silesia in Katowice

AIMTo investigate serum omentin and vaspin levels in cirrhotic patients; and to assess the relationship of these levels with hemostatic parameters, metabolic abnormalities, cirrhosis severity and ***-one cirrhotic patients (17 with portal vein thrombosis) were analyzed. Serum omentin and vaspin levels were measured with commercially available direct enzyme-linked immunosorbent assays (ELISAs). To assess platelet activity, the following tests were performed using a MULTIPLATE®PLATELET FUNCTION ANALYZER: (1) an ADP-induced platelet activation test; (2) a cyclooxygenase dependent aggregation test (ASPI test); (3) a von Willebrand factor and glycoprotein Ib-dependent aggregation (using ristocetin) test (RISTO test); and (4) a test for thrombin receptor-activating peptide-6 induced activation of the thrombin receptor, which is sensitive to IIb/IIIa receptor ***, but not vaspin, serum concentrations were significantly decreased in patients with portal vein thrombosis (PVT) (P = 0.01). Prothrombin levels were significantly increased in patients with PVT (P = 0.01). The thrombin receptor activating peptide (TRAP) test results were significantly lower in the PVT group (P = 0.03). No significant differences in adipokines serum levels were found regarding the etiology or severity of liver cirrhosis assessed according to the Child-Pugh or Model of End-Stage Liver Disease (MELD) scores. There was a significant increase in the TRAP (P = 0.03), ASPI (P = 0.001) and RISTO high-test (P = 0.02) results in patients with lower MELD scores. Serum omentin and vaspin levels were significantly down-regulated in patients without insulin resistance (P = 0.03, P = 0.02, respectively). A positive relationship between omentin and vaspin levels were found both when all of the patients were analyzed (r = 0.41, P = 0.01) and among those with PVT (r = 0.94, P < 0.001).CONCLUSIONSerum omentin levels are increased in patients without PVT. Cirrhosis

关键词： Omentin vaspin Cirrhosis Adipokine Portal vein thrombosis Portal hypertension

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Associations between vaspin Levels and Coronary Artery Disease

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Cardiovascular Innovations and Applications 2020年第1期4卷 211-216页

作者： Lutfu Askin Okan Tanriverdi Hakan Tibilli Serdar Turkmen Department of Cardiology Adiyaman Education and Research HospitalAdiyamanTurkey

The relationship between serum vaspin levels and metabolic or coronary artery disease is currently of interest for *** adipokine concentrations have been shown to be increased signifi cantly in atherosclerotic lesions,the role adipokines in the atherosclerotic process remains to be *** is a new biological marker associated with obesity and impaired insulin *** vaspin concentration has been shown to correlate with the severity of coronary artery *** infl ammation triggered by vaspin inhibits atherogenesis by suppressing macrophage foam cell formation and vascular smooth muscle cell migration and *** also contributes to plaque stabilization by increasing collagen content and reducing the intraplaque macrophage to vascular smooth muscle cell *** therapeutic goal concerning vaspin is to fi ght atherosclerosis and related diseases,as well as to maintain vascular health.

关键词： adipokine atherosclerosis infl ammation coronary artery disease vaspin

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vaspin通过PI3K/Akt通路发挥抗炎及血管内皮保护作用减轻脂多糖致急性呼吸窘迫综合征小鼠肺损伤

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南方医科大学学报 2018年第3期38卷 283-288页

作者：李雯戚迪陈兰赵燕邓旺唐旭毛王导新重庆医科大学附属第二医院呼吸内科重庆400010

目的探讨vaspin对LPS致ARDS小鼠的保护作用及其可能机制。方法 40只雄性C57BL/6J小鼠按随机数字表分为对照组、LPS组、vaspin组和wortmannin(PI3K抑制剂)组,每组10只。苏木精-伊红(HE)染色观察肺组织病理改变,肺湿干比评估肺水肿,BCA法... 详细信息

目的探讨vaspin对LPS致ARDS小鼠的保护作用及其可能机制。方法 40只雄性C57BL/6J小鼠按随机数字表分为对照组、LPS组、vaspin组和wortmannin(PI3K抑制剂)组,每组10只。苏木精-伊红(HE)染色观察肺组织病理改变,肺湿干比评估肺水肿,BCA法检测支气管肺泡灌洗液(BALF)中蛋白含量,评估肺组织通透性改变;髓过氧化物酶(MPO)试剂盒检测肺组织MPO活性,ELISA检测肺组织中白细胞介素(IL-1β)和肿瘤坏死因子(TNF-α)的含量,免疫组织化学法(IHC)观察肺组织中VCAM-1表达;Western blot法检测肺组织cleaved caspase-3和Akt磷酸化水平。结果与对照组比较,LPS组小鼠肺组织呈现典型ARDS病理改变,肺组织湿干比W/D值、BALF蛋白含量、肺组织MPO活性、IL-1β和TNF-α水平,肺组织VCAM-1表达及cleaved caspase-3蛋白表达水平显著增高(Pvaspin干预能显著缓解上述变化(Pvaspin组相比,其湿干比W/D值、BALF蛋白含量、MPO活性和IL-1β、TNF-α及cleaved caspase-3蛋白表达水平显著升高(Pvaspin可通过其介导的抗炎、抗凋亡及血管内皮保护效应对LPS致ARDS肺损伤发挥保护性调控,其可能机制为上调了PI3K/Akt通路。

关键词：急性呼吸窘迫综合征 vaspin 炎症血管内皮 PI3K/Akt

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vaspin在糖尿病心肌病中的作用及机制研究

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中国药理学通报 2018年第10期34卷 1403-1408页

作者：柯旋李宾公郝艳琴李雪莲邹晋南昌大学第一附属医院心内科江西南昌330006 武汉市第三医院心内科湖北武汉430000 江西省人民医院心内科江西南昌330006

目的观察内脏脂肪丝氨酸蛋白酶抑制剂vaspin对糖尿病心肌病(diabetic cardiomyopathy, DCM)大鼠心肌纤维化及心功能的影响。方法♂SD大鼠一次性腹腔注射链脲霉素(60 mg·kg^(-1))制备糖尿病模型,模型成功后12周为DCM组,对照组腹腔注射... 详细信息

目的观察内脏脂肪丝氨酸蛋白酶抑制剂vaspin对糖尿病心肌病(diabetic cardiomyopathy, DCM)大鼠心肌纤维化及心功能的影响。方法♂SD大鼠一次性腹腔注射链脲霉素(60 mg·kg^(-1))制备糖尿病模型,模型成功后12周为DCM组,对照组腹腔注射生理盐水(0.5 mL·kg^(-1)·d^(-1)),vaspin组为模型成功后腹腔注射vaspin(320 ng·kg^(-1)·d^(-1))。心脏彩超观察大鼠左室射血分数(LVEF)、短轴收缩率(FS)、左室舒张末内径(LVEDd)、左室收缩末内径(LVEDs),并检测E峰/A峰(Em/Am);ELISA检测大鼠血清中TNF-α水平;Masson染色检测心肌胶原纤维,并分析胶原容积分数(CVF);Western blot测定心肌组织中自噬及凋亡蛋白表达。结果与对照组相比,DCM组TNF-α升高(Pvaspin组LVEF、FS、Em/Am升高(P0.05)。结论 vaspin可增加DCM大鼠心肌组织自噬水平,改善DCM大鼠心肌纤维化。

关键词： vaspin 自噬心肌纤维化糖尿病心肌病凋亡氧化应激

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Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha

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Chinese Medical Journal 2010年第7期123卷 936-941页

作者： WANG You-min WANG Wen-ping WANG Li-ping LU Qi-huan ZHOU Xiao-hui Institute of Endocrinology & Metabolism Anhui Medical University Department of Endocrinology First Affiliated Hospital of Anhui Medical University Hefei Anhui 230022 China

Background vaspin was recently identified as a novel adipokine that is predominantly secreted from adipose tissue and exerts insulin-sensitizing effects. This study was undertaken to elucidate the regulative effects of calorie control on the expression of vaspin and its potential *** Diet-induced obese Sprague Dawley （SD） rats were adopted as experimental models and accepted interventions of various ingestions and pioglitazone. Various differentiated stages of cultured 3T3-L1 cells were dealt with pioglitazone or TNFα in vitro for 48 hours to further verify findings in animal *** The rats were successfully induced into an obese experimental model with hyperinsulinemia, hyperlipidemia, and increased serum free fatty acid and TNFa by 12-week high-fat diet. It was found that depending on whether the rats were fed by a high-fat diet or a basal diet, there was extremely higher vaspin in the periepididymal fat pad than in subcutaneous adipose tissues by 16 weeks. vaspin in sera and the periepididymal fat pad was much lower in rats with a high-fat diet than those with a basal diet （all P 〈0.05）, but vaspin in subcutaneous fat tissues was prone to increase in rats with a high-fat diet. A 4-week calorie restriction or pioglitazone on the obese rats resulted in a partial recovery of vaspin levels in sera and periepididymal adipose tissues, especially the latter revealed a more obvious superiority and increased vaspin levels of subcutaneous adipose. Surprisingly, the treatment of 4-week high-fat diet on non-obese rats did not significantly depress vaspin of sera and periepididymal adipose tissues. However, it is unknown if re-feeding generated the effect on vaspin levels of obese and non-obese rats on sera or adipose tissues. The correlation analysis showed that vaspin levels of serum and periepididymal fat tissues were negatively correlated with serum FFA, TNFα and insulin; meanwhile, there was a positive correlation between serum vaspin and vasp

关键词： vaspin diet-induced obese rats pioglitazone calorie control

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vaspin通过胰岛素信号通路改善地塞米松诱导的3T3-L1脂肪细胞的胰岛素抵抗

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西安交通大学学报（医学版） 2018年第3期39卷 366-370页

作者：刘萍农晰婷刘晓霞张薇武金娥周鑫成淑英孙超峰西安市第三医院内分泌科陕西西安710018 西安市中心医院内分泌科陕西西安710003 西安交通大学第一附属医院心内科陕西西安710061

目的探讨vaspin对胰岛素抵抗脂肪细胞3T3-L1信号通路的作用及其机制。方法前脂肪细胞3T3-L1经地塞米松、IBMX及胰岛素混合诱导剂诱导8d,分化成为成熟脂肪细胞。(1)不同质量浓度vaspin(0、50、100、200ng/mL)处理成熟3T3-L1细胞,观察PAKT... 详细信息

目的探讨vaspin对胰岛素抵抗脂肪细胞3T3-L1信号通路的作用及其机制。方法前脂肪细胞3T3-L1经地塞米松、IBMX及胰岛素混合诱导剂诱导8d,分化成为成熟脂肪细胞。(1)不同质量浓度vaspin(0、50、100、200ng/mL)处理成熟3T3-L1细胞,观察PAKT/AKT通路的变化。(2)采用1μmol/L地塞米松建立胰岛素抵抗模型。分化成熟的脂肪细胞随机分为4组:对照组、模型对照组、实验组、vaspin 200ng/mL+wortmannin 100nmol/L组。(3)观察vaspin作用不同时间对胰岛素抵抗脂肪细胞葡萄糖消耗量的影响,Western blot分析胰岛素信号通路IRS-1、磷脂酰肌醇3激酶(PI3K)及Akt/phospho-Akt蛋白表达。结果 (1)vaspin(0、50、100、200ng/mL)干预成熟脂肪细胞12h,vaspin以浓度依赖的方式增加PAKT蛋白表达,与对照组相比,在100、200ng/mL组均有统计学差异(P0.05)。(3)与对照组相比,模型对照组的IRS-1、PI3K、PAKT的蛋白表达低于对照组,差异有统计学意义(Pvaspin对PAKT/AKT、PI3K、IRS-1蛋白表达的上调。结论 vaspin通过影响胰岛素抵抗的脂肪细胞中的PAKT/AKT胰岛素信号通路,增加葡萄糖的利用,改善了地塞米松诱导的3T3-L1脂肪细胞的胰岛素抵抗。

关键词： vaspin 胰岛素抵抗脂肪细胞胰岛素信号通路

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vaspin：一种新的脂肪源性丝氨酸蛋白酶抑制物

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中华内分泌代谢杂志 2009年第4期25卷 469-470页

作者：叶银贾伟平上海交通大学附属第六人民医院内分泌代谢科 200233

vaspin是新发现的由脂肪细胞特异性表达的脂肪细胞因子，属丝氨酸蛋白酶抑制物家族。研究发现它具有改善胰岛素敏感性的作用，在肥胖、尤其是体脂含量增加时表达增加。但目前对vaspin与胰岛素敏感性之间的相关性研究尚存在分歧，需要进... 详细信息

vaspin是新发现的由脂肪细胞特异性表达的脂肪细胞因子，属丝氨酸蛋白酶抑制物家族。研究发现它具有改善胰岛素敏感性的作用，在肥胖、尤其是体脂含量增加时表达增加。但目前对vaspin与胰岛素敏感性之间的相关性研究尚存在分歧，需要进行大样本的临床研究进一步明确两者的关系。

关键词： vaspin 胰岛素敏感性肥胖糖尿病 2型丝氨酸蛋白酶抑制剂

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vaspin、肥胖及2型糖尿病

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中华内分泌代谢杂志 2011年第5期27卷 448-450页

作者：刘师伟王金华杨静山西医科大学第一医院内分泌科太原030001 美国洛杉矶圣约翰医学中心

vaspin是一种新发现的内脏脂肪因子，具有胰岛素增敏效应。最近研究显示，重组vaspin干预饮食诱导的肥胖小鼠可明显改善胰岛素敏感性和糖耐量，逆转胰岛素抵抗相关基因的表达。然而，胰岛素抵抗患者血清vaspin水平的调节以及其与肥胖、... 详细信息

vaspin是一种新发现的内脏脂肪因子，具有胰岛素增敏效应。最近研究显示，重组vaspin干预饮食诱导的肥胖小鼠可明显改善胰岛素敏感性和糖耐量，逆转胰岛素抵抗相关基因的表达。然而，胰岛素抵抗患者血清vaspin水平的调节以及其与肥胖、2型糖尿病及胰岛素抵抗相关疾病的关系尚不清楚。

关键词：脂肪细胞因子 vaspin 肥胖糖尿病, 2型胰岛素抵抗

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用阻塞性睡眠呼吸暂停低通气综合征动物模型研究vaspin与胰岛素信号通路的相关性

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中国病理生理杂志 2014年第11期30卷 2084-2088页

作者：庄向华倪一虹刘元涛孙爱丽孙福敦姜冬青李晓博陈诗鸿山东大学第二医院内分泌科山东济南250033

目的:通过建立阻塞性睡眠呼吸暂停低通气综合征(OSAHS)大鼠模型,检测其vaspin的血清学以及mRNA、蛋白水平的表达特点,阐述脂肪因子vaspin在OSAHS发生过程中的作用机制。方法:用慢性间歇低氧(CIH)模拟OSAHS。健康雄性Wistar大鼠22只,随... 详细信息

目的:通过建立阻塞性睡眠呼吸暂停低通气综合征(OSAHS)大鼠模型,检测其vaspin的血清学以及mRNA、蛋白水平的表达特点,阐述脂肪因子vaspin在OSAHS发生过程中的作用机制。方法:用慢性间歇低氧(CIH)模拟OSAHS。健康雄性Wistar大鼠22只,随即分为空白对照(control)组和CIH组。每天将CIH组大鼠放入间歇性低氧舱内,共8周。实验前后应用大鼠尾压测量仪测量血压。实验结束后处死动物,检测空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素(FINS)、vaspin和脂联素。应用实时荧光定量PCR和蛋白印迹法(Western blotting)检测vaspin mRNA以及vaspin、Akt、p-Akt蛋白水平。结果:(1)慢性间歇性缺氧下血气结果:缺氧最低点时大鼠动脉血氧分压23.4 mm Hg^32.8 mm Hg,最低血氧饱和度范围为40.8%~65.9%,恢复舱内氧浓度至21%后,测得动脉血氧分压为74.5 mm Hg^102.9 mm Hg,动脉血氧饱和度为93.8%~98.9%。(2)实验前后2组大鼠之间比较体重均无显著差异;血压变化实验前2组大鼠尾动脉收缩压无显著差异,实验后2组大鼠之间比较,CIH组大鼠收缩压明显高于正常对照组。CIH组和control组比较,FPG、FINS、TG和TC均升高,差别有统计学意义(Pvaspin水平与FPG、FINS、HOMA-IR和TC呈正相关。(4)CIH组大鼠脂肪组织的vaspin mRNA和蛋白质的表达水平均增加,差别有统计学意义(Pvaspin;水平的改变可能在胰岛素抵抗发生过程中具有一定作用。

关键词：阻塞性睡眠呼吸暂停低通气综合征 vaspin 胰岛素信号通路

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