LncRNAs are one group of gene modulators functioning via several mechanisms in pathological and physiological conditions. We noted that LINC00472 expression level is elevated in atherosclerotic coronary tissues compared with normal coronary artery samples. LINC00472 is also upregulated in vascular smooth muscle cells (VSMCs) induced by TNF-α and PDGF-BB. Ectopic expression of LINC00472 induced VSMC migration and proliferation. The predicted binding sequence between miR-149-3p and LINC00472 was analyzed by LncBase Predicted. Overexpression of miR-149-3p decreases the luciferase activity of wild-type reporter plasmid, but not the mutant one. Ectopic expression of LINC00472 suppresses the expression of miR-149-3p in VSMCs. Furthermore, we demonstrated that miR-149-3p expression is decreased in atherosclerotic coronary tissues. MiR-149-3p was downregulated in VSMCs induced by TNF-α and PDGF-BB. Overexpression of LINC00472 induces VSMC migration and proliferation via regulating miR-149-3p. These data suggested that LINC00472 acts a critical role in the migration and proliferation of VSMCs partly via modulating miR-149-3p.

The yolk sac is the first site of blood-cell production during embryonic development in both murine and human. Heat shock proteins (HSPs), including HSP70 and HSP27, have been shown to play regulatory roles during erythropoiesis. However, it remains unknown whether HSP60, a molecular chaperone that resides mainly in mitochondria, could also regulate early erythropoiesis. In this study, we used Tie2-Cre to deactivate the Hspd1 gene in both hematopoietic and vascular endothelial cells, and found that Tie2-Cre+Hspd1f/f (HSP60CKO) mice were embryonic lethal between the embryonic day 10.5 (E10.5) and E11.5, exhibiting growth retardation, anemia, and vascular defects. Of these, anemia was observed first, independently of vascular and growth phenotypes. Reduced numbers of erythrocytes, as well as an increase in cell apoptosis, were found in the HSP60CKO yolk sac as early as E9.0, indicating that deletion of HSP60 led to abnormality in yolk sac erythropoiesis. Deletion of HSP60 was also able to reduce mitochondrial membrane potential and the expression of the voltage-dependent anion channel (VDAC) in yolk sac erythrocytes. Furthermore, cyclosporine A (CsA), which is a well-recognized modulator in regulating the opening of the mitochondrial permeability transition pore (mPTP) by interacting with Cyclophilin D (CypD), could significantly decrease cell apoptosis and partially restore VDAC expression in mutant yolk sac erythrocytes. Taken together, we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism.

Background Endothelial NO synthase plays a central role in regulating vasodilation and blood pressure. Intracellular Ca2+ mobilization is a critical modulator of endothelial NO synthase function, and increased cytosolic Ca2+ concentration in endothelial cells is able to induce endothelial NO synthase phosphorylation. Ca2+ release mediated by 3 subtypes of inositol 1,4,5‐trisphosphate receptors (IP3Rs) from the endoplasmic reticulum and subsequent Ca2+ entry after endoplasmic reticulum Ca2+ store depletion has been proposed to be the major pathway to mobilize Ca2+ in endothelial cells. However, the physiological role of IP3Rs in regulating blood pressure remains largely unclear. Methods and Results To investigate the role of endothelial IP3Rs in blood pressure regulation, we first generated an inducible endothelial cell–specific IP3R1 knockout mouse model and found that deletion of IP3R1 in adult endothelial cells did not affect vasodilation and blood pressure. Considering all 3 subtypes of IP3Rs are expressed in mouse endothelial cells, we further generated inducible endothelial cell–specific IP3R triple knockout mice and found that deletion of all 3 IP3R subtypes decreased plasma NO concentration and increased basal blood pressure. Furthermore, IP3R deficiency reduced acetylcholine‐induced vasodilation and endothelial NO synthase phosphorylation at Ser1177. Conclusions Our results reveal that IP3R‐mediated Ca2+ release in vascular endothelial cells plays an important role in regulating vasodilation and physiological blood pressure.

Background Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) are a family of intracellular Ca 2+ release channels located on the membrane of endoplasmic reticulum, which have been shown to play critical roles in various cellular and physiological functions. However, their function in regulating gastrointestinal (GI) tract motility in vivo remains unknown. Here, we investigated the physiological function of IP 3 R1 in the GI tract using genetically engineered mouse models. Methods Pdgfrb - Cre mice were bred with homozygous Itpr1 floxed ( Itpr1 f/f ) mice to generate conditional IP 3 R1 knockout (pcR1KO) mice. Cell lineage tracing was used to determine where Pdgfrb - Cre -mediated gene deletion occurred in the GI tract. Isometric tension recording was used to measure the effects of IP 3 R1 deletion on muscle contraction. Results In the mouse GI tract, Itpr1 gene deletion by Pdgfrb - Cre occurred in smooth muscle cells, enteric neurons, and interstitial cells of Cajal. pcR1KO mice developed impaired GI motility, with prolonged whole-gut transit time and abdominal distention. pcR1KO mice also exhibited lethality as early as 8 weeks of age and 50% of pcR1KO mice were dead by 40 weeks after birth. The frequency of spontaneous contractions in colonic circular muscles was dramatically decreased and the amplitude of spontaneous contractions was increased in pcR1KO mice. Deletion of IP 3 R1 in the GI tract also reduced the contractile response to the muscarinic agonist, carbachol, as well as to electrical field stimulation. However, KCl-induced contraction and expression of smooth muscle-specific contractile genes were not significantly altered in pcR1KO mice. Conclusions Here, we provided a novel mouse model for impaired GI motility and demonstrated that IP 3 R1 plays a critical role in regulating physiological function of GI tract in vivo.

Background Previous studies have shown that beta 2-microglobulin (B2M) could predict all-cause mortality and cardiovascular mortality in various groups of people. However, the relationship between B2M and severity of coronary stenosis in patients with acute coronary syndrome has not been established. Methods We enrolled 872 consecutive patients admitted with acute coronary syndrome in our study. All participants underwent coronary angiography examination or stent implantation after admission. The severity of coronary stenosis was assessed by Gensini score and the presentation of triple-vessel disease. B2M and other biochemical parameters were measured. All subjects were divided into quartiles of B2M. Multivariate linear regression and logistic regression were applied in the analysis. Results Gensini score and the prevalence of triple-vessel disease were elevated in accordance with increasing B2M quartiles (p = 0.002 and p < 0.001, respectively). Multivariate regression showed diabetes (p = 0.031), high-sensitivity C-reactive protein (hs-CRP, p = 0.043) and B2M (p = 0.006) were positively correlated with Gensini score. Logistic regression analysis revealed that the crude and fully adjusted odds ratios of triple-vessel disease were 2.34 (95% CI: 1.58-3.46) and 1.97 (95% CI: 1.14-3.40) in the fourth quartile of B2M compared with the first quartile, respectively. However, no interactive relationships were found in subgroup analysis by estimated glomerular filtration rate or hs-CRP in the above associations, neither in the distribution of Gensini score (p for interaction>0.05 for both). Conclusion Our data indicated that B2M was an independent risk factor of coronary stenosis in patients with acute coronary syndrome.

Dual antiplatelet therapy (DAPT) score and PRECISE-DAPT score were recommended for decision making of optimal DAPT in discriminating the risk of thrombosis and bleeding. But the relationships between 2 scoring tools with the extent of coronary stenosis have not been established.We retrospectively enrolled 359 patients of acute coronary syndrome (ACS) who received percutaneous coronary intervention. Both DAPT score and PRECISE-DAPT score were calculated, and patients were divided by their recommended cut-offs. Gensini score and triple-vessel disease (3-VD) were chosen to evaluate the severity of coronary stenosis.Overall, 54.9% and 10.0% of the patients had higher DAPT score (≥2) or PRECISE-DAPT score (≥25). Patients with higher DAPT score had increased stent counts, total length of stents, Gensini score, and proportion of 3-VD, but decreased minimum diameter of stent. But these differences were not found in PRECISE-DAPT subgroups. When divided into quartiles of both scoring systems, the highest Gensini score and proportions of 3-VD were found in the fourth quartile of both DAPT score and PRECISE-DAPT score. Moreover, both DAPT score and PRECISE-DAPT score were independent risk factors of Gensini score after adjustment (P < .001 and P = .047). Furthermore, an increase of 1 point of DAPT score and 5 points of PRECISE-DAPT score resulted by 51% (odds ratios [OR]: 1.51, 95% confidence interval [CI]:1.19-1.91, P = .001) and 34% (OR: 1.34, 95% CI: 1.11-1.62, P = .003) increase in risk of 3-VD after adjustment.Both DAPT score and PRECISE-DAPT score were independently associated with the degree of coronary stenosis in patients with ACS.

The epigenetic changes underlying the development of rheumatic heart valve disease (RHVD) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of RHVD. In the present study, we evaluated the DNA methylation dysregulations from myocardial tissue in RHVD patients systematically.

microRNA-99a (miR-99a) is recently recognized as a key regulator in various cancers and cardiovascular diseases. In the present study, we sought to investigate the effects of miR-99a in rat cardiomyocyte H9c2 cells against oxidative injury induced by lipopolysaccharide (LPS).MTT assay, reactive oxygen species (ROS) assay, flow cytometry and lactate dehydrogenase (LDH) assay were respectively used to explore viability, ROS levels, apoptosis, and cell death in H9c2 cells. Quantitative PCR (qRT-PCR) was performed to confirm the expression of miR-99a. Western blot was performed to determine the expression of Notch pathway factors.LPS could significantly suppress viability and increase cell death, apoptosis, and ROS level (P < 0.05). However, miR-99a could significantly increase the viability and decrease apoptosis and ROS level of H9c2 cells (P < 0.05). Overexpression of miR-99a could activate a Notch pathway and regulate the expression of B-cell CLL/lymphoma 2 (BCL2) and cleaved caspase 3.Our study found that overexpression of miR-99a could attenuate LPS-induced oxidative injury in H9c2 cells, possibly via a Notch pathway. These findings suggest that miR-99a may be a key factor in cardiomyocyte oxidative injury and could be a new therapeutic strategy for cardiovascular diseases.

Inositol 1, 4, 5-trisphosphate receptor-mediated (IP3R-mediated) calcium (Ca2+) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle-specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca2+ release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction. We demonstrated that deletion of IP3Rs significantly reduced aortic contractile responses to vasoconstrictors, including phenylephrine, U46619, serotonin, and endothelin 1. Deletion of IP3Rs also dramatically reduced the phosphorylation of MLC20 and MYPT1 induced by U46619. Furthermore, although the basal blood pressure of smTKO mice remained similar to that of wild-type controls, the increase in systolic blood pressure upon chronic infusion of angiotensin II was significantly attenuated in smTKO mice. Taken together, our results demonstrate an important role for IP3R-mediated Ca2+ release in VSMCs in regulating vascular contractility and hypertension.

目的 总结心电图表现为巨大Epsilon波致心律失常右室心肌病(ARVC)患者的临床和心电图特点.方法 分析本院于2011年1月至2014年12月收治的12导联心电图示巨大Epsilon波ARVC患者的临床和心电图特点.通过查询Medline、CNKI、VIP和万方数据库等总结该心电图特征ARVC患者的特点.结果 5例患者中男性4例.首发症状均为心悸、头昏.发作时心电图为右室起源室性心动过速.心脏超声示右室扩大;右室壁变薄,可见小凹.心电图V1导联QRS呈“M”型;巨大Epsilon波振幅为(0.37±0.16)mV,振幅与S波比值为1.20±0.23;持续时间为(90±12.75)ms,持续时间与QRS波相比为0.60±0.06.文献报道5例患者均为男性.临床表现为心悸,晕厥发作.心电图V1导联QRS均呈rsR ',Fontain导联、心向量和晚电位证实该R '波为Epsilon波.V1导联Ep-silon波振幅为(0.52±0.35)mV,振幅与S波比值为1.18±0.74;持续时间(96.0±11.4)ms,持续时间与QRS波相比为0.65±0.08.结论 临床上巨大Epsilon波ARVC患者少见,右室激动延缓,心律失常发生率高.

Objective To explore the clinical characteristics and the possible pathogenesis for transient aphasia induced by head-up tilt test (HUTT).Methods The data of 4 401 cases (aged from 2 to 79 years) were reviewed retrospectively with unexplained syncope,pre-syncope,or dizziness who had visited syncope specialists at out-patient department or had been hospitalized in the Second Xiangya Hospital of Central South University,and they underwent HUTT from Sep.2000 to Apr.2014.The clinical characteristics were summarized and the possible pathogenesis for transient aphasia was analyzed.Results (1) The total incidence of aphasia was 3.18‰(14/4 401 cases).The incidence in adult(≥18 years old) was significantly higher than that in children(＜ 18 years old) [7.0‰(9/1 284 cases) vs 1.6‰(5/3 117 cases),x2 =6.76,P ＜ 0.01],but there was no difference between the male and female [1.91‰(4/2 091 cases) vs 4.33‰(10/2 310 cases),x2 =1.33,P ＞ 0.05].According to the hemodynamic changes,the incidences in vasodepressor,the mixed type,cardioinhibition and the negative response were 6.05‰ (10/1 654 cases),4.18‰(2/479 cases),0 (0/36 cases) and 0.9‰ (2/2 232 cases) respectively,and the differences among the 4 groups were significant (x2 =8.22,P ＜ 0.05) ; the difference existed between the vasodepressor and the negative response(x2 =8.18,P ＜ 0.01).The total incidence of the positive response patients was 5.53‰(12/2 169 cases),and the difference was notable compared with the negative response patients (x2 =6.07,P ＜ 0.05).(2)The onset time and the duration time of transient aphasia:the onset time was from 4 to 17 minutes during baseline head-up tilt test,mean (11.3 ± 6.7) minutes,or 2-10 minutes during sublingual nitroglycerin-provocated head-up tilt test,mean (5.2 ±2.7) minutes.Aphasia duration was from 3 minutes to 4 hours,and the median time was 20 minutes.Conclusions There is a risk of provoking transient aphasia during HUTT,which reminds that the performer should alert possible occurrence of this complication during the test,especially when the patient has a positive response,or is an adult.

目的 采用24 h动态血压(ABPM)方法探讨直立性高血压(OHT)患儿的血压类型.方法 选取2009年10月至2013年9月在中南大学湘雅二医院(我院)儿童晕厥门诊就诊或住院的患儿,以不明原因晕厥及先兆晕厥为主诉,经直立倾斜试验确诊为OHT者为OHT组.与OHT组年龄及性别匹配,选择同期来我院儿童保健门诊检查的健康儿童为对照组.OHT组和对照组均行ABPM监测,观察收缩压昼夜差值、舒张压昼夜差值,24 h、日间、夜间平均收缩压和舒张压参数,并探讨血压类型.结果 OHT组40例,男23例,女17例,年龄(11.5±1.9)岁.对照组40例,男22例,女18例,年龄(10.6±2.4)岁.①收缩压昼夜差值对照组高于OHT组,(9.8±3.3) vs (8.4±4.7) mmHg,P＜0.05.OHT组24 h、日间、夜间的平均收缩压和舒张压稍高于对照组(P＞0.05).舒张压昼夜差值对照组稍高于OHT组(P＞0.05).②OIIT组以非勺型血压为主(72.5％),对照组以勺型血压为主(55.0％),两组血压类型差异有统计学意义(P=0.012).结论 OHT患儿收缩压昼夜差值较正常儿童明显降低,血压类型以非勺型血压多见,多数患儿血压昼夜节律消失.

Background-The striated muscle Z-line, a multiprotein complex at the boundary between sarcomeres, plays an integral role in maintaining striated muscle structure and function. Multiple Z-line-associated proteins have been identified and shown to play an increasingly important role in the pathogenesis of human cardiomyopathy. Cypher and its close homologue, Enigma homolog protein (ENH), are 2 Z-line proteins previously shown to be individually essential for maintenance of postnatal cardiac function and stability of the Z-line during muscle contraction, but dispensable for cardiac myofibrillogenesis and development.Methods and Results-The current studies were designed to test whether Cypher and ENH play redundant roles during embryonic development. Here, we demonstrated that mice lacking both ENH and Cypher exhibited embryonic lethality and growth retardation. Lethality in double knockout embryos was associated with cardiac dilation and abnormal Z-line structure. In addition, when ENH was ablated in conjunction with selective ablation of either Cypher short isoforms (CypherS), or Cypher long isoforms (CypherL), only the latter resulted in embryonic lethality.Conclusions-Cypher and ENH redundantly play an essential role in sustaining Z-line structure from the earliest stages of cardiac function, and are redundantly required to maintain normal embryonic heart function and embryonic viability.

目的 总结儿童体位性心动过速(POTS) 24 h动态血压监测(ABPM)变化特点.方法 回顾性分析2009年1月至2013年6月因不明原因晕厥先兆、晕厥症状在中南大学湘雅二医院儿童晕厥门诊就诊或住院,经直立倾斜试验(HUTT)诊断明确并同时行ABPM的70例POTS患儿,年龄4～14岁.对照组为同期来门诊进行体检的健康儿童,年龄4～14岁.根据血压昼夜节律将两组再分成“勺型”血压和“非勺型”血压两种情况,并进行比较.结果 (1) POTS组昼夜平均血压均低于对照组(P＞0.05).收缩压昼夜差值亦低于对照组(P＜0.05),而舒张压昼夜差值在两组差异无统计学意义(P＞0.05).(2)血压昼夜节律:“非勺型”血压在POTS组高于对照组(72.9％ vs.45.0％,P＜0.01).POTS组日间平均收缩压、收缩压昼夜差值、舒张压昼夜差值在“勺型”血压亚组高于“非勺型”血压亚组(P＜0.05),而夜间平均收缩压、夜间平均舒张压在“勺型”血压亚组低于“非勺型”血压亚组(P＜0.05).结论 POTS儿童平均血压与健康儿童无明显差异,但POTS儿童血压昼夜节律以“非勺型”血压多见.

OBJECTIVE To study the time-dependent heart rate (HR) variability in the head-up tilt test (HUTT) in children with postural orthostatic tachycardia syndrome (POTS) and to explore the HR diagnostic criteria for POTS in children. METHODS A retrospective analysis was performed on the clinical data of 105 children diagnosed with POTS with HR≥120 beats per minute (bpm) within the first 10 minutes of HUTT between January 2007 and December 2014. Their HR variability within the first 10 minutes of HUTT was analyzed. RESULTS The HR of children with POTS increased gradually from the supine position to a 60° head-up tilt position, and the increase in HR was 24±12 bpm at the beginning of HUTT, 30±14 bpm at 3 minutes of HUTT, 32±13 bpm at 5 minutes of HUTT, and 38±12 bpm at 10 minutes of HUTT. The average maximal HR increase within the first 10 minutes of HUTT was 43±10 bpm. CONCLUSIONS In children with POTS, the HR variability gradually increases with time, and therefore, it is suggested that HR increase ≥40 bpm is more suitable for diagnosis of POTS in children.

Objective: To investigate the correlation between growth differentiation factor 15 (GDF 15) + 157 A/T polymorphism and the formation of collateral circulation in acute non-ST segment elevated myocardial infarction in Han population of Shandong province. Method: The medical records of 200 cases of patients undergoing selective coronary angiography were analyzed, and the arterial blood specimens of included patients were collected before coronary angiography. Based on the results of coronary angiography, patients were divided into acute myocardial infarction (AMI) group and normal control group; AMI group was divided into collateral group and non-collateral group by Rentrop's grading method; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to analyze the GDF 15 + 157 A/T polymorphism in the two groups. Results: There were statistically significant differences in GDF 15 + 157 A/T AA and AT distribution between AMI group and the control group (P = 0.002); and there was statistically significant difference in allele frequencies between the two groups (P = 0.006); for AMI group, there were statistically significant differences in GDFAA and AT genotype distribution between patients with and without collateral (P = 0.014), and there was statistically significant difference in allele frequencies between the two (P = 0.025). Conclusion: There was correlation between GDF 15 + 157 A/T polymorphism and the formation of collateral circulation in patients with non-ST-segment elevated myocardial infarction.

体位改变可引起心电图变化，卧位、立位心电图对心血管自主神经功能的评价具有临床意义。该文介绍了卧位与立位时的心电图 P 波、QRS 波群、QT 间期、T 波和 ST 段改变情况和其对心血管自主神经功能评价的意义。

Objective To retrospectively analyze the changes of 24 h ambulatory blood pressure monitoring (ABPM) in children with orthostatic hypertension (OHT).Methods The patients from Jan.2008 to Dec.2013 were selected,who had the chief complain of unexplained syncope and pre-syncope,through the head-up tilt test (HUTT) diagnosed as OHT [n =43,male 25 cases,female 18 cases,aged (11.56 ± 1.88) years old] according to the age and gender match,chief complaint of unexplained syncope or pre-syncope,through the HUTT diagnosed as simple vasovagal syncope (VVS) [n =49,male 28 cases,female 21 cases,aged (11.16 ± 2.18) years old].The ABPM was recorded of every child 1 d before or after HUTT.Results 1.ABPM parameters:daytime mean systolic pressure was higher in OHT group than that in VVS group (t ＝ 2.332,P ＜ 0.05),hut 24 hour mean systolic pressure,24 hour mean diastolic pressure,daytime mean diastolic pressure,nighttime mean systolic pressure,nighttime mean diastolic pressure,systolic pressure differences and diastolic pressure differences in the daytime and nighttime had no statistical differences between OHT group and VVS group (t =1.975,1.334,1.540,1.156,0.617,0.957 and 0.969,all P ＞ 0.05).2.Blood pressure change in 3 min of HUTT:the diastolic blood pressure change in 3 min of HUTT in OHT group was higher than that in the VVS group (t =2.132,P ＜ 0.05),but the systolic blood pressure and diastolic blood pressure in horizontal position,systolic blood pressure and diastolic blood pressure in 3 min of HUTT,the systolic blood pressure change in 3 min of HUTT had no statistical differences between OHT group and VVS group (t =1.101,0.030,2.062,1.632 and 1.811,all P ＞ 0.05).3.Blood type:" non-dipper blood pressure" was the main blood type in OHT group and VVS group,and there was no statistically significant difference between the 2 groups (x2 =0.005,P ＞ 0.05).Conclusions In OHT children,daytime mean systolic pressure and diastolic blood pressure change in 3 min of HUTT increased,and "non-dipper blood pressure" is the main blood type.These may be associated with autonomic nerve dysfunction.

美国的医疗体系正在发生转变，这种转变使得医疗部门更多地关注疾病危险因素的早期识别和管理，特别是对于心血管疾病（CVD）。医疗机构不能只是在医院等临床医疗单元推行心血管疾病危险因素的早期识别和管理，更应该积极的与用人单位，学校，社区基层的医疗服务站点和公共卫生部门合作，力图改善心血管疾病防治的现状。也就是说应该重新认识预防的重要性。目前，最为激烈的争论就是是否必须将现有的利益导向型医疗经济转换为预防为主的医疗环境。