Zhen-Guo Ma1,2,3, Yu-Pei Yuan1,2,3, Si-Chi Xu1,2,3, Wen-Ying Wei1,2,3, Chun-Ru Xu1,2,3, Xin Zhang1,2,3, Qing-Qing Wu1,2,3, Hai-Han Liao1,2,3, Jian Ni1,2,3, Qi-Zhu Tang4,5,6,7. 1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China. 2. Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China. 3. Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China. 4. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China. qztang@whu.edu.cn. 5. Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China. qztang@whu.edu.cn. 6. Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China. qztang@whu.edu.cn. 7. Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Hubei Key Laboratory of Cardiology, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China. qztang@whu.edu.cn.
Abstract
AIMS/HYPOTHESIS: Oxidative stress, inflammation and cell death are closely involved in the development of diabetic cardiomyopathy (DCM). C1q/tumour necrosis factor-related protein-3 (CTRP3) has anti-inflammatory properties but its role in DCM remains largely unknown. The aims of this study were to determine whether CTRP3 could attenuate DCM and to clarify the underlying mechanisms. METHODS: Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in Sprague-Dawley rats. Cardiomyocyte-specific CTRP3 overexpression was achieved using an adeno-associated virus system 12 weeks after STZ injection. RESULTS: CTRP3 expression was significantly decreased in diabetic rat hearts. Knockdown of CTRP3 in cardiomyocytes at baseline resulted in increased oxidative injury, inflammation and apoptosis in vitro. Cardiomyocyte-specific overexpression of CTRP3 decreased oxidative stress and inflammation, attenuated myocyte death and improved cardiac function in rats treated with STZ. CTRP3 significantly activated AMP-activated protein kinase α (AMPKα) and Akt (protein kinase B) in H9c2 cells. CTRP3 protected against high-glucose-induced oxidative stress, inflammation and apoptosis in vitro. AMPKα deficiency abolished the protective effects of CTRP3 in vitro and in vivo. Furthermore, we found that CTRP3 activated AMPKα via the cAMP-exchange protein directly activated by cAMP (EPAC)-mitogen-activated protein kinase kinase (MEK) pathway. CONCLUSIONS/ INTERPRETATION: CTRP3 protected against DCM via activation of the AMPKα pathway. CTRP3 has therapeutic potential for the treatment of DCM.
AIMS/HYPOTHESIS: Oxidative stress, inflammation and cell death are closely involved in the development of diabetic cardiomyopathy (DCM). C1q/tumour necrosis factor-related protein-3 (CTRP3) has anti-inflammatory properties but its role in DCM remains largely unknown. The aims of this study were to determine whether CTRP3 could attenuate DCM and to clarify the underlying mechanisms. METHODS:Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in Sprague-Dawley rats. Cardiomyocyte-specific CTRP3 overexpression was achieved using an adeno-associated virus system 12 weeks after STZ injection. RESULTS: CTRP3 expression was significantly decreased in diabeticrat hearts. Knockdown of CTRP3 in cardiomyocytes at baseline resulted in increased oxidative injury, inflammation and apoptosis in vitro. Cardiomyocyte-specific overexpression of CTRP3 decreased oxidative stress and inflammation, attenuated myocyte death and improved cardiac function in rats treated with STZ. CTRP3 significantly activated AMP-activated protein kinase α (AMPKα) and Akt (protein kinase B) in H9c2 cells. CTRP3 protected against high-glucose-induced oxidative stress, inflammation and apoptosis in vitro. AMPKα deficiency abolished the protective effects of CTRP3 in vitro and in vivo. Furthermore, we found that CTRP3 activated AMPKα via the cAMP-exchange protein directly activated by cAMP (EPAC)-mitogen-activated protein kinase kinase (MEK) pathway. CONCLUSIONS/ INTERPRETATION: CTRP3 protected against DCM via activation of the AMPKα pathway. CTRP3 has therapeutic potential for the treatment of DCM.
Authors: D Bryant; L Becker; J Richardson; J Shelton; F Franco; R Peshock; M Thompson; B Giroir Journal: Circulation Date: 1998-04-14 Impact factor: 29.690
Authors: J Kajstura; F Fiordaliso; A M Andreoli; B Li; S Chimenti; M S Medow; F Limana; B Nadal-Ginard; A Leri; P Anversa Journal: Diabetes Date: 2001-06 Impact factor: 9.461
Authors: Risa M Wolf; Kimberley E Steele; Leigh A Peterson; Thomas H Magnuson; Michael A Schweitzer; G William Wong Journal: PLoS One Date: 2015-07-29 Impact factor: 3.240