Xie Jun, He Guixin, Chen Qinhua, Sun Jiayin, Dai Qin, Lu Jianrong, Li Guannan, Wu Han, Li Ran, Chen Jianzhou, Xu Wei, Xu Biao
Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
Department of Cardiology, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Mol Med. 2016 Sep;22:192-201. doi: 10.2119/molmed.2015.00026. Epub 2016 Jan 21.
Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4 compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy.
心脏肥大可大致分为生理性或病理性。运动等生理刺激会导致适应性心脏肥大和正常心脏功能。包括高血压和主动脉瓣狭窄在内的病理刺激会导致适应性不良的心脏重塑并最终导致心力衰竭。Syndecan-4（synd4）是一种跨膜蛋白聚糖，已被确定参与损伤后的心脏适应，但它是否参与生理性心脏肥大尚不清楚。我们观察到运动诱导的肥厚心肌中synd4上调。为了评估synd4在生理性心脏肥大中的作用，对缺乏synd4（synd4-/-）的小鼠进行了4周的游泳运动。超声心动图（UCG）和组织学分析显示，游泳诱导了肥厚表型，但与野生型（WT）小鼠相比，synd4-/-小鼠的这种表型减弱。游泳诱导的Akt激活是生理性肥大的关键分子，其激活程度也比WT对照组更明显降低。在培养的心肌细胞中，synd4过表达可诱导细胞增大、蛋白质合成和明显的生理分子变化。在synd4过表达的心肌细胞中也观察到Akt激活。此外，蛋白激酶C（PKC）的抑制可阻止synd4诱导的肥厚表型和Akt磷酸化。本研究确定了synd4在介导生理性心脏肥大中的重要作用。
