AIMS:Tissue kallikrein-related peptidase 8 (KLK8) plays a significant role in the regulation of cardiac remodeling following myocardial infarction (MI). However, the impact of KLK8 on macrophage (MΦ) function in the context of MI remains to be elucidated. MATERIALS AND METHODS:MI was induced through the ligation of the left anterior descending coronary artery for a duration of 1 h, followed by reperfusion. The morphological and molecular alterations in the heart were assessed at 24 h and 14 days post-ischemic injury. Adult rat cardiac fibroblasts and bone marrow-derived macrophages were employed to explore the underlying molecular mechanisms in vitro. KEY FINDINGS:In the acute phase of MI (24 h post-MI), KLK8 was observed to diminish the inflammatory response and mitigate tissue damage within the ischemic ventricle. Conversely, during the reparative phase of MI (14 days post-MI), KLK8 was found to enhance the accumulation of the M2 MΦs, elevate pro-fibrotic factors, and intensify cardiac fibrosis. The in vitro analysis revealed that KLK8 did not exert a direct effect on MΦs; rather, it facilitated the paracrine secretion of epidermal growth factor (EGF) from the cardiac fibroblasts. This EGF may play a role in inhibiting the pro-inflammatory activation of the MΦs and promoting their polarization towards the M2 phenotype under conditions of inflammatory stress. SIGNIFICANCE:In summary, KLK8 modulates MΦ function through the paracrine of EGF derived from cardiac fibroblasts, which may have implications for cardiac injury and remodeling following MI.

Aims: Endothelial-mesenchymal transition (EndMT) is a crucial pathological process contributing to cardiac fibrosis. Bradykinin has been found to protect the heart against fibrosis. Whether bradykinin regulates EndMT has not been determined. Materials and methods: Rats were subjected to ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion to induce cardiac ischemia-reperfusion (IR) injury. Bradykinin (0.5 mu g/h) was infused by an osmotic pump implanted subcutaneously at the onset of reperfusion. Fourteen days later, the functional, histological, and molecular analyses were performed to investigate the changes in cardiac fibrosis and EndMT. Human coronary artery endothelial cells were utilized to determine the molecular mechanisms in vitro. Results: Bradykinin treatment improved cardiac function and decreased fibrosis following cardiac IR injury, accompanied by ameliorated EndMT and increased nitric oxide (NO) production. In vitro experiments found that bradykinin mitigated transforming growth factor 81 (TGF81)-induced EndMT. Significantly, the bradykinin B2 receptor antagonist or endothelial nitric oxide synthase inhibitor abolished the effects of bradykinin on EndMT inhibition, indicating that the bradykinin B2 receptor and NO might mediate the effects of bradykinin on EndMT inhibition. Conclusion: Bradykinin plays an essential role in the process of cardiac fibrosis. Bradykinin preserves the cellular signature of endothelial cells, preventing them from EndMT following cardiac IR injury, possibly mediated by bradykinin B2 receptor activation and NO production.

国际生理学知识竞赛(inter-medical school physiology quiz,IMSPQ)是目前亚太地区最有影响力的医学类国际竞赛之一.培训和参加IMSPQ是一项有意义的基础医学教育课题,能拓展生理学教学的广度和深度,实现教学相长,使学生掌握生理学知识的同时提高教师的教学能力.通过多年参赛,海军军医大学形成一套培训模式,主要包括:带队教师采用轮换制,提升教师教学水平;选拔学生采用淘汰制,督促学生自主学习;培训方式以自学和讨论为主,深化学生对知识的理解和应用;组织校内生理学知识竞赛,扩大竞赛的影响.

Aims: Tissue kallikrein-related peptidase8 (KLK8) has been found to mitigate acute myocardial ischemiareperfusion (IR) injury. However, the effect of KLK8 on cardiac remodeling in response to IR injury has not been determined. Materials and methods: KLK8 overexpressing transgenic rat (KLK8-TG) was used as the animal model. IR injury was induced by ligating the left anterior descending coronary artery for 1 h and subsequent reperfusion. The functional and morphological changes of the heart were examined 14 days after the injury. Neonatal rat cardiac fibroblasts (CFs) were used to investigate the molecular mechanisms in vitro. Key findings: KLK8 overexpression enhanced cardiac diastolic dysfunction, fibrosis, and hypertrophy after IR injury, indicating that KLK8 accentuated cardiac remodeling in response to IR injury. Moreover, KLK8 overexpression increased epidermal growth factor (EGF) release and promoted the phosphorylation of EGF receptor (EGFR) and ERK1/2 in the heart after IR injury. It was interesting to find that both EGFR antagonist (AG 1478) and MEK inhibitor (PD98059) attenuated the KLK8-induced proliferation and activation of CFs in vitro, indicating that EGFR signaling might mediate the pro-fibrotic action of KLK8. Significance: KLK8 plays a crucial role in cardiac remodeling after myocardial infarction. KLK8 accentuates cardiac fibrosis after IR injury, possibly mediated by EGFR signaling in CFs.

Background: Dexmedetomidine (DEX) has been reported to protect the heart against ischemia reperfusion (I/R) injury. However, the exact mechanisms are still not fully understood. Methods and results: A rat cardiac I/R injury model was induced by ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion for 2 h, and DEX was administered intravenously 30 min before ischemia. We confirmed that DEX treatment mitigated cardiac I/R injury. Interestingly, we found that DEX regulated the expression of bradykinin (BK) receptors (B1R and B2R) in rat hearts during I/R injury and enhanced the protective action of BK administered during reperfusion. Moreover, in vitro hypoxia reoxygenation (H/R) injury was induced in neonatal rat cardiomyocytes (CMs), and DEX was administered 1 h before hypoxia. The in vitro findings were consistent with the in vivo experiments. We found that an alpha 2-adrenoceptor (alpha 2-AR) antagonist (yohimbine) completely aborted DEX-induced B1R and B2R regulation; an adenylyl cyclase (AC) agonist (forskolin) blocked B1R downregulation, while a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) blocked B2R upregulation. The above findings indicated that DEX interacted with alpha 2-AR in cardiomyocytes, inhibited B1R expression via suppression of AC, and stimulated B2R expression via activation of PI3K. Conclusions: DEX regulates BK receptor expression and potentiates the protection of BK in cardiac I/R injury, which suggests that modulating endogenous cardioprotective factors may play an important role in DEX-induced cardioprotection.

生理学是研究人体生命活动规律的学科,是构筑医学生医学理论体系、培养科学素质的重要基础.随着国家对外开放,医学生国际交流日益频繁,深化医学专业英语教学的需求变得更加迫切.结合海军军医大学生理学教研室多年的生理学教学经验,探索出在生理学教学中整合医学英语培训的新模式,并提出从学科教育出发、语言教育并重、结合PBL的系统教学理念.文章主要从教学准备、实施和效果评价三方面阐述教学经验.

目的 探讨组织激肽释放酶1(KLK1)对心脏缺血/再灌注损伤大鼠线粒体功能的影响及其机制.方法 通过KLK1重组腺病毒感染实现大鼠心脏KLK1过表达,然后采用冠状动脉左前降支结扎和再灌注的方法建立大鼠心脏缺血/再灌注损伤模型,检测梗死区面积和心脏缺血危险区细胞凋亡情况;分离大鼠心脏缺血危险区心肌组织线粒体,检测线粒体功能(线粒体过氧化物生成量、线粒体膜电位、线粒体ATP生成量).分离新生大鼠心肌细胞,通过KLK1重组腺病毒感染实现KLK1过表达,然后建立心肌细胞缺氧/复氧损伤模型,对心肌细胞缺氧/复氧损伤模型应用缓激肽1型受体(B1R)阻断剂R715或缓激肽2型受体(B2R)阻断剂HOE140处理,利用MTT法检测细胞活力,并观察线粒体功能的变化.结果 在大鼠心脏缺血/再灌注损伤模型中,KLK1过表达能减轻心肌缺血/再灌注损伤,使心肌梗死区面积减小、缺血危险区细胞凋亡减少(P均<0.01);改善心脏缺血/再灌注损伤后线粒体功能障碍,降低过氧化物生成量、增加线粒体膜电位和线粒体ATP生成量(P均<0.01).在离体大鼠心肌细胞缺氧/复氧模型中,KLK1过表达能减轻心肌细胞损伤(P<0.05)、改善线粒体功能障碍(P<0.05,P<0.01),并且其作用可被B2R阻断剂HOE140抑制.结论 KLK1能改善心脏缺血/再灌注损伤后线粒体功能障碍,这可能是其具有心脏保护作用的重要机制.

Tissue kallikrein-related peptidases (KLKs) play important roles in acute cardiac injury and cardiac remodeling. However, the exact cardiac actions of KLK8 have not been determined. Transgenic rat overexpressing KLK8 was established to examine the role of KLK8 in the heart. Cardiac injury was induced by ischemia/reperfusion (I/R) and examined by infarct size measurement and TUNEL staining. The molecular mechanisms were investigated in cultured neonatal rat cardiomyocytes (CMs). Western blot analysis was used to determine the protein levels. KLK8 protein level was significantly increased in the cardiac ischemic risk area. KLK8 overexpression mitigated I/R-induced cardiac injury, as evidenced by decreased infarct size and apoptosis in cardiac ischemic risk area in vivo. Via in vitro studies, it was found that KLK8 overexpression attenuated the Hypoxia/Reoxygenation (H/R) injury in CMs; both B2R and PAR2 antagonist significantly attenuated KLK8-induced protective actions under H/R injury. Moreover, KLK8 overexpressed CMs showed significant higher phosphorylation levels of Akt, ERK1/2 and PKA under H/R stimulation; B2R antagonist attenuated the phosphorylation levels of Akt and ERK1/2, while PAR2 antagonist attenuated the phosphorylation levels of PKA and ERK1/2. KLK8 protects the heart against I/R-induced cardiac injury, which may represent a new therapeutic target in cardiac medicine.

Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. The regeneration capacity of the adult mammalian heart is very limited, so that the lost cells are replaced by fibrotic scar. This is followed by remodeling of the surrounding myocardium, which includes cardiac hypertrophy and fibrosis, and makes the ventricular wall thicken and stiffen. This adverse cardiac remodeling leads to impaired cardiac function and eventually leads to heart failure. Extensive studies have revealed that microRNAs (miRNAs) play an essential role in cardiovascular diseases. microRNA-22 (miR-22) is one of the most abundant miRNA in the heart. Many studies have demonstrated that miR-22 plays critical roles in MI and subsequent cardiac remodeling. In this review, we summarized the recent research progresses, including the regulatory effects of miR-22 in oxidative stress, cardiac apoptosis, autophagy, hypertrophy, fibrosis and regeneration.

根据多年来进行国际生理学竞赛培训和竞赛指导中积累的经验，通过对竞赛赛制、题型和参考教材的深入分析，建立了覆盖面广、题量大、细节化和灵活性高的国际生理竞赛全英文试题库，并在竞赛培训时进行应用。使用过程中不断吸收参训学员的反馈意见，及时更新和改进试题库以使其不断完善，从而确保实现竞赛培训的最优效果。

The tissue kallikrein-related peptidase family (KLK) is a group of trypsin-and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus-mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling-and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling.

Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function. We found that miR-22 level was significantly increased in rat hearts subjected to I/R injury, as compared with the sham group. Intra-myocardial injection of 20 ug miR-22 inhibitor reduced I/R injury as evidenced by significant decreases in cardiac infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels and the number of apoptotic cardiomyocytes. H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) insult exhibited an increase in miR-22 expression, which was blocked by reactive oxygen species (ROS) scavenger and p53 inhibitor. In addition, miR-22 inhibitor attenuated, whereas miR-22 mimic aggravated H/R-induced injury in H9c2 cardiomyocytes. MiR-22 inhibitor per se had no significant effect on cardiac mitochondrial function. Mitochondria from rat receiving miR-22 inhibitor 48 h before ischemia were found to have a significantly less mitochondrial superoxide production and greater mitochondrial membrane potential and ATP production as compared with rat receiving miR control. In H9c2 cardiomyocyte, it was found that miR-22 mimic aggravated, whilst miR-22 inhibitor significantly attenuated H/R-induced mitochondrial damage. By using real time PCR, western blot and dual-luciferase reporter gene analyses, we identified Sirt1 and PGC1α as miR-22 targets in cardiomyocytes. It was found that silencing of Sirt1 abolished the protective effect of miR-22 inhibitor against H/R-induced mitochondrial dysfunction and cell injury in cardiomyocytes. Taken together, our findings reveal a novel molecular mechanism for cardiac mitochondrial dysfunction during myocardial I/R injury at the miRNA level and demonstrate the therapeutic potential of miR-22 inhibition for acute myocardial I/R injury by maintaining cardiac mitochondrial function.

基于计算机多媒体技术的虚拟实验室,作为一种新的实验教学手段而受到重视. 虚拟实验的优势在于可以弥补真实动物实验中的技术缺陷. 然而,虚拟实验在激发学生学习兴趣,锻炼学生科学思维方面存在显著不足. 文章对虚拟实验的利弊做了分析,并提供了实际应用的基本模式.

国际医学生生理学知识竞赛由马来亚大学医学院主办，为来自世界各地的生理学教师和医学生提供了很好的交流平台。通过竞赛，与国际一流医学院校交流，学习他们先进的教学理念和经验，在教学实践中进行双语教学、强调对生理学知识的理解和应用、注重以问题为中心的小组讨论，提高了生理学理论课教学质量。

Objective To study the regulatory effects of long non-coding RNA HIF1A-AS1 on the myocardial ischemia reperfusion(I/R)injury and the related mechanism.Methods Myocardial I/R injury model was established with SD rats,and hypoxia reoxygenation(H/R)model was established with rat cardiac myocytes.si-HIF1A-AS1 was used to inhibit HIF1A-AS1 expression in the cardiac myoctyes.Then the mRNA expression of HIF1A-AS1 was detected by real-time PCR,the growth vitality of cardiac myocytes was investigated by MTT assay,the concentration of lactate dehydrogenase(LDH)in the culture media was detected by ELISA,and the autophagy-associated protein Beclin-1expression was observed by Western blotting analysis.Results HIF1A-AS1 expression was increased in cardiac muscle of rat I/R model and rat cardiac myocytes of H/R model.Inhibition of HIF1A-AS1 by siRNA protected the cardiomyocytes against H/R injuries,reversing the decreased growth vitality of cardiac myoctyes,increased LDH level in the culture media,and increased expression of autophagy-related protein Beclin-1induced by H/R stimulation.Conclusion Inhibition of long non-coding RNA HIF1A-AS1 might play aprotective role in I/R injury of cardiac myoctyes by inhibiting the excessive autophagy of cardiomyocytes.

Exercise training has been looked on as a non-pharmacologic approach to treating ovariectomy (OVX)-induced dysfunctions. In this study, we investigated whether chronic exercise impacts on expression of urocortins (UCNs) and corticotropin-releasing hormone receptor type 2 (CRHR2) in myocardium of OVX rats. Bilateral OVX or sham-operation was performed under anesthesia. Both groups were then divided into two subgroups, with or without treadmill training for 8 weeks. It was found that OVX as well as exercise did not affect the mRNA levels of UCN, UCN2 and UCN3 in myocardium. OVX caused down-regulation of CRHR2 in myocardium. Exercise training reversed the OVX-induced reduction of CRHR2, but had no influence on CRHR2 level in sham rats. OVX resulted in a decrease in estrogen receptor α (ERα) expression in myocardium, which was restored by exercise. Moreover, exercise training also reversed OVX-induced down-regulation of specific protein-1 (Sp-1) expression in myocardium. CRHR2 expression level correlated with Sp-1 and ERα level in myocardium. These results indicate that exercise training can restore the CRHR2 level in myocardium of OVX rats, which is associated with ERα and Sp-1 expression.

第二军医大学基础部自2011年以来，首先在临床医学八年制专业进行课程体系整合，主要采用“以器官系统为中心”的形态和功能课程整合的教学模式，分别从教学理念转变、教学团队建设、课程整合、教材建设、教学实施及教学效果评估等教学环节的各个方面进行了教学改革。文章介绍了生理学教研室在泌尿生殖系统形态和功能整合课程中，采用“以问题为主线”的教学模式，贯彻“以学生为主体、教师为主导”的教学理念进行的探索与实践。

Background Urocortin-1 (UCN1) exerts protective effects on hypoxia/reoxygenation injury in the heart. Serum- and glucocorticoid- responsive kinase-1 (SGK1), a serine-threonine kinase, has been shown to be crucial for cardiomyocyte survival. The purpose of the present study was to investigate whether SGK1 is involved in UCN1-induced cardioprotection. Methods Cardiomyocytes were obtained from neonatal rats and used as a model to investigate UCN1 regulation of SGK1. Specific small interfering RNA targeting SGK1 was used to knock down SGK1 expression. The messenger RNA (mRNA) level of SGK1 was measured using quantitative real time reverse transcription polymerase chain reaction, and the protein levels of SGK1 and phosphorylated SGK1 were determined using Western blot analysis. Results SGK1 knockdown attenuated the protective effects of UCN1 against hypoxia/reoxygenation injury in cardiomyocytes. Treatment of cardiomyocytes with UCN1 stimulated SGK1 mRNA and protein expression and time-dependently increased phosphorylated SGK1 level. These effects were completely reversed with corticotrophin-releasing hormone receptor type 2 antagonist. Adenylate cyclase and protein kinase A inhibitors abolished the stimulatory effect of UCN1 on SGK1 expression. SGK1 phosphorylation induced by UCN1 was blocked by phosphorinositide-3-kinase inhibitor. Conclusions SGK1 is involved in the cardioprotective effects of UCN1 in cardiomyocytes. UCN1 stimulates SGK1 phosphorylation via the phosphorinositide-3-kinase signalling pathway and it induces SGK1 expression via the adenylate cyclase/protein kinase A pathway.

Serum and glucocorticoid-responsive kinase1 (SGK1) is a serine–threonine kinase, which has been reported to play a key role in cell survival in various tissues including the myocardium [[1]Aoyama T. Matsui T. Novikov M. Park J. Hemmings B. Rosenzweig A. Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response.Circulation. 2005; 111: 1652-1659Crossref PubMed Scopus (104) Google Scholar]. As estrogen has cardioprotective effects [[2]Murphy E. Estrogen signaling and cardiovascular disease.Circ. Res. 2011; 109: 687-696Crossref PubMed Scopus (266) Google Scholar], we explored whether SGK1 contributes to estrogen cardioprotection. As shown in Fig. 1, ovariectomized (Ovx) rats showed deceased SGK1 mRNA and protein expression in the myocardium, which was reversed by 17β-estradiol (E2, 30 μg/kg/day, sc) replacement for 8 weeks. In order to elucidate whether estrogen modulates SGK1 expression in cardiomyocytes, we examined the effects of E2 on SGK1 expression in neonatal rat cardiomyocytes in vitro. It was found that treatment with E2 (0.1–100 nmol/L) for 24 h did not affect SGK1 mRNA and protein levels in cardiomyocytes (Fig. 1B), which indicates that E2 might regulate SGK1 expression via an indirect mechanism in the myocardium. Recently, we demonstrated that urocortin1 (UCN1) protects cardiomyocytes against hypoxia/reoxygenation (H/R) insult through up-regulation of SGK1 expression [[3]Cong B. Wang L. Zhu X. Li X. Liu B. Ni X. SGK1 is involved in cardioprotection of urocortin-1 against hypoxia/reoxygenation in cardiomyocytes.Can. J. Cardiol. 2014; 30: 687-695Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar], and E2 plays a critical role in the maintenance of corticotrophin-releasing hormone receptor 2 (CRHR2) expression in cardiomyocytes [4Cong B. Zhu X. Cao B. Xiao J. Wang Z. Ni X. Estrogens protect myocardium against ischemia/reperfusion insult by up-regulation of CRH receptor type 2 in female rats.Int. J. Cardiol. 2013; 168: 4755-4760Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 5Cong B. Xu Y. Sheng H. Zhu X. Wang L. Zhao W. Tang Z. Lu J. Ni X. Cardioprotection of 17β-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2.Mol. Cell. Endocrinol. 2014; 382: 17-25Crossref PubMed Scopus (17) Google Scholar]. We therefore hypothesized that E2 might enhance UCN1-induced SGK1 expression. Primary cardiomyocytes were treated with E2 (10 nmol/L) plus UCN1 (10 nmol/L) for 24 h. Compared with UCN1 treatment alone, E2 did increase SGK1 mRNA and protein levels in the presence of UCN1 (Fig. 1C). As UCN1 has been shown to be released from cardiomyocytes under ischemia [[6]Knight R.A. Chen-Scarabelli C. Yuan Z. et al.Cardiac release of UCN precedes the occurrence of irreversible myocardial damage in the rat heart exposed to I/R injury.FEBS Lett. 2008; 582: 984-990Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], we examined whether E2 increases SGK1 expression under H/R condition. Treatment of cardiomyocytes with E2 (10 nmol/L) under the simulated H/R condition resulted in an increase in SGK1 expression, which was abolished by CRHR2 antagonist (Fig. 1D). These data indicate that E2 induces SGK1 expression under H/R, which might be through enhancement of the UCN1 effect. To examine whether SGK1 is involved in the cardioprotective effects of E2, we knocked down SGK1 expression by specific SGK1 siRNA, and then the cardioprotective effects of E2 upon H/R in cardiomyocytes were examined. As shown in Fig. 2, the E2 induced increasing cell viability, decreasing LDH release and inhibiting cleaved caspase 3 level were all attenuated by SGK1 siRNA (Fig. 2A–C). These data indicate that SGK1 involves in E2 cardioprotection against H/R injury. In summary, our data demonstrated that E2 regulates SGK1 expression via enhancing UCN1 action in the myocardium, which contributes to cardioprotective effects of E2 against H/R. These findings provide new evidences that UCN1-CRHR2 system plays important roles in the cardiac effect of E2 [4Cong B. Zhu X. Cao B. Xiao J. Wang Z. Ni X. Estrogens protect myocardium against ischemia/reperfusion insult by up-regulation of CRH receptor type 2 in female rats.Int. J. Cardiol. 2013; 168: 4755-4760Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 5Cong B. Xu Y. Sheng H. Zhu X. Wang L. Zhao W. Tang Z. Lu J. Ni X. Cardioprotection of 17β-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2.Mol. Cell. Endocrinol. 2014; 382: 17-25Crossref PubMed Scopus (17) Google Scholar]. However, our findings that SGK1 is involved in E2 cardioprotection were on the basis of experiments in vitro. Further studies are required to confirm the role of SGK1 in estrogen cardioprotection. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.