Medicine and Health Sciences Commons^™

Serum Ctrp9 And High-Molecular Weight Adiponectin Are Associated With Ischemic Stroke., Yan-Qing Zhang, Yan-Wei Zhang, Jian-Li Dai, Chen Li, Wen-Qing Wang, Hai-Feng Zhang, Wayne Bond Lau, Xiao-Ming Wang, Xiao-Gang Liu, Rong Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke.

METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured.

RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke …

Adiponectin Partially Rescues High Glucose/High Fat-Induced Impairment Of Mitochondrial Biogenesis And Function In A Pgc-1Α Dependent Manner., H. Wang, W.-J. Yan, J.-L. Zhang, F.-Y. Zhang, C. Gao, Y.-J. Wang, W.B. Lau, L. Tao

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms.

MATERIALS AND METHODS: Neonatal rat ventricular myocytes (NRVMs) were isolated and incubated in HGHF medium. Mitochondrial function was assessed by ATP content, and fluorescent microscopic analysis of myocardial apoptosis …

Adiponectin Ameliorates The Apoptotic Effects Of Paraquat On Alveolar Type Ⅱ Cells Via Improvements In Mitochondrial Function., Yarong He, Liqun Zou, Yaxiong Zhou, Hai Hu, Rong Yao, Yaowen Jiang, Wayne Bond Lau, Tun Yuan, Wen Huang, Zhi Zeng, Yu Cao

Department of Emergency Medicine Faculty Papers

Previous studies have demonstrated that excessive reactive oxygen/nitrogen species (ROS/RNS)‑induced apoptosis is an important feature of the injury to the lung epithelium in paraquat (PQ) poisoning. However the precise mechanisms of PQ‑induced dysfunction of the mitochondria, where ROS/RNS are predominantly produced, remain to be fully elucidated. Whether globular adiponectin (gAd), a potent molecule protective to mitochondria, regulates the mitochondrial function of alveolar type II cells to reduce PQ‑induced ROS/RNS production remains to be investigated. The current study aimed to investigate the precise mechanisms of PQ poisoning in the mitochondria of alveolar type II cells, and to elucidate the role of …

Adiporon, The First Orally Active Adiponectin Receptor Activator, Attenuates Postischemic Myocardial Apoptosis Through Both Ampk-Mediated And Ampk-Independent Signalings., Yanqing Zhang, Jianli Zhao, Rui Li, Wayne Bond Lau, Yue-Xing Yuan, Bin Liang, Rong Li, Er-He Gao, Walter J. Koch, Xin-Liang Ma, Ya-Jing Wang

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) is a cardioprotective molecule. Its reduction in diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury. Although APN administration in animals attenuates MI/R injury, multiple factors limit its clinical application. The current study investigated whether AdipoRon, the first orally active molecule that binds APN receptors, may protect the heart against MI/R injury, and if so, to delineate the involved mechanisms. Wild-type (WT), APN knockout (APN-KO), and cardiomyocyte specific-AMPK dominant negative (AMPK-DN) mice were treated with vehicle or AdipoRon (50 mg/kg, 10 min prior to MI) and subjected to MI/R (30 min/3-24 h). Compared with vehicle, oral administration of AdipoRon to WT …

Adiponectin Attenuates Lung Fibroblasts Activation And Pulmonary Fibrosis Induced By Paraquat., Rong Yao, Yu Cao, Ya-Rong He, Wayne Bond Lau, Zhi Zeng, Zong-An Liang

Department of Emergency Medicine Faculty Papers

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different …

Adiponectin Inhibits Oxidative/Nitrative Stress During Myocardial Ischemia And Reperfusion Via Pka Signaling., Yanqing Zhang, Xiao-Liang Wang, Jianli Zhao, Ya-Jing Wang, Wayne Bond Lau, Yue-Xing Yuan, Er-He Gao, Walter J. Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

The cardioprotective effects of adiponectin (APN) against myocardial ischemia/reperfusion (MI/R) injury are well known. However, comprehension of the mechanisms mediating intracellular APN signaling remains incomplete. We recently demonstrate the antioxidant/antinitrative effects of APN are not dependent on AMPK. Protein kinase A (PKA) has been previously shown to be activated by APN, with uncertain relevance to APN cardiac protection. The current study determined whether the antioxidative/antinitrative effect of APN is mediated by PKA. Administration of APN (2 μg/g) 10 min before reperfusion significantly enhanced cardiac PKA activity, reduced oxidative stress, and decreased infarct size. Knockdown of cardiac PKA expression (PKA-KD) by …

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Reduced Cardioprotective Action Of Adiponectin In High-Fat Diet-Induced Type Ii Diabetic Mice And Its Underlying Mechanisms., Wei Yi, Yang Sun, Erhe Gao, Xufeng Wei, Wayne Bond Lau, Qijun Zheng, Yajing Wang, Yuexing Yuan, Xiaoliang Wang, Ling Tao, Rong Li, Walter Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent …

Systemic Adiponectin Malfunction As A Risk Factor For Cardiovascular Disease., Wayne Bond Lau, Ling Tao, Yajing Wang, Rong Li, Xin L Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad's metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad's anti-inflammatory …

Dynamic Alteration Of Adiponectin/Adiponectin Receptor Expression And Its Impact On Myocardial Ischemia/Reperfusion In Type 1 Diabetic Mice., Yanzhuo Ma, Yi Liu, Shaowei Liu, Yan Qu, Rutao Wang, Chenhai Xia, Haifeng Pei, Kun Lian, Tao Yin, Xiaoyan Lu, Lu Sun, Lu Yang, Yanjie Cao, Wayne Bond Lau, Erhe Gao, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The present study determined the dynamic change of adiponectin (APN, a cardioprotective adipokine), its receptor expression, and their impact upon myocardial ischemia/reperfusion (MI/R) injury during type 1 diabetes mellitus (T1DM) progression, and involved underlying mechanisms. Diabetic state was induced in mice via multiple intraperitoneal injections of low-dose streptozotocin. The dynamic change of plasma APN concentration and cardiac APN receptor-1 and -2 (AdipoR1/2) expression were assessed immediately after diabetes onset (0 wk) and 1, 3, 5, and 7 wk thereafter. Indicators of MI/R injury (infarct size, apoptosis, and LDH release) were determined at 0, 1, and 7 wk of DM duration. …

Cardiomyocyte-Derived Adiponectin Is Biologically Active In Protecting Against Myocardial Ischemia-Reperfusion Injury., Yajing Wang, Wayne Bond Lau, Erhe Gao, Ling Tao, Yuexing Yuan, Rong Li, Xiaoliang Wang, Walter J. Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) has traditionally been viewed as an adipocyte-specific endocrine molecule with cardioprotective effects. Recent studies suggest that APN is also expressed in cardiomyocytes. However, biological significances of this locally produced APN remain completely unknown. The aim of this study was to investigate the pathological and pharmacological significance of cardiac-derived APN in cardiomyocyte pathology. Adult cardiomyocytes from wild-type littermates (WT) or gene-deficient mice were pretreated with vehicle (V) or rosiglitazone (RSG) for 6 h followed by simulated ischemia-reperfusion (SI/R, 3 h/12 h). Compared with WT cardiomyocytes, myocytes from APN knockout (APN-KO) mice sustained greater SI/R injury, evidenced by greater oxidative/nitrative …

Cardioprotective Effect Of Adiponectin Is Partially Mediated By Its Ampk-Independent Antinitrative Action., Yajing Wang, Ling Tao, Yuexing Yuan, Wayne Bond Lau, Rong Li, Bernard L. Lopez, Theodore A. Christopher, Rong Tian, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (I/R) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice overexpressing a dominant-negative alpha(2)-subunit of AMPK (AMPK-DN) or wild-type (WT) littermates were subjected to simulated I/R (SI/R) and pretreated with 2 microg/ml globular domain of APN (gAPN) or vehicle. SI/R-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes (P < 0.05). Treatment with gAPN significantly reduced SI/R-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SI/R-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect.