Lymphangiogenesis contributes to exercise-induced physiological cardiac growth  

作　　者：Yihua Bei Zhenzhen Huang Xing Feng Lin Li Meng Wei Yujiao Zhu Shuqin Liu Chen Chen Mingming Yin Huimin Jiang Junjie Xiao 

机构地区：[1]Cardiac Regeneration and Ageing Lab,Institute of Geriatrics(Shanghai University),Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong),School of Medicine,Shanghai University,Nantong 226011,China [2]Shanghai Engineering Research Center of Organ Repair,School of Life Science,Shanghai University,Shanghai 200444,China [3]Clinical Laboratory Center,Beijing Hospital of Traditional Chinese Medicine,Beijing 100010,China

出　　处：《Journal of Sport and Health Science》2022年第4期466-478,共13页运动与健康科学（英文）

基　　金：supported by the grants from National Key Research and Development Project(2018YFE0113500 to JX);National Natural Science Foundation of China(82020108002 and 81911540486 to JX,81970335 and 82170285 to YB);Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to JX);Science and Technology Commission of Shanghai Municipality(20DZ2255400 and 18410722200 to JX);the“Dawn”Program of Shanghai Education Commission(19SG34 to JX);the Shanghai Rising-Star Program(19QA1403900 to YB);the Science and Technology Commission of Shanghai Municipality(21SQBS00100 to YB).

摘　　要：Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes.However,it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth.We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth.Methods:Adult C57 BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth.Oral treatment with vascular endothelial growth factor receptor 3(VEGFR3) inhibitor SAR1 3 1 675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation.Furthermore,human dermal lymphatic endothelial cell(LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy.Results:Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels.VEGFR3 was upregulated in the exercised heart,while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes,which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise.Furthermore,LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulinlike growth factor-1 and the extracellular protein Reelin,while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects.Functional rescue assays further demonstr

关 键 词：Cardiac lymphatics Exercise Physiological cardiac hypertrophy Proliferation VEGFR3 

分 类 号：G804.2[文化科学—运动人体科学] R542.2[文化科学—体育学]