The Concordance Rates between LV Hypertrophy and RV Hypertrophy in Patients with Hypertrophic Cardiomyopathy as Diagnosed by Cardiovascular MRI with Fibrosis Imaging

Introduction: CMR has become the leading modality to define the clinical impact of hypertrophic cardiomyopathy (HCM). Late gadolinium enhancement (LGE) accurately identifies regions of myocardial fibrosis. It is well known that myocardial fibrosis can occur in patients with HCM and is independently linked to a poorer prognosis than those without fibrosis by CMR. Hypothesis: We hypothesize that there is significant RV involvement in HCM when incorporates a CMR analysis for RV hypertrophy and fibrosis. Methods: A retrospective review of all patients referred for HCM was performed. SSFP/LGE techniques were used to diagnose patients with HCM, using gadolinium administration (0.15 mmol/kg). Post-injection (10 minutes) LGE images were obtained using manual T1-weighted, IR-preparations. Regions of myocardium with LGE signals were visually designated as fibrotic. LV/RV mass indices (LVMI/RVMI) and ejection fractions were calculated. Results: Via 72 patients referred for HCM, 47(65%) were CMR confirmed. The mean LVMI was 108 ± 44 g/m2 while the mean RVMI was 30 ± 21 g/m2. As well, 34/47 (72%) had evidence of LV fibrosis while 24/47 (51%) had evidence for RV fibrosis. Of the RVH positive patients, 26/34 (76%) patients were LV LGE positive and 18/34 (52%) were RV LGE positive. Conclusion: The high frequency of RVH and RV fibrosis in the setting of HCM is surprising in that this phenomenon is rarely described. However, there is no reason to expect the phenotypic expression should be limited to the LV. Interestingly, as for the LV, the presence or absence of RV fibrosis has little predictive power towards the systolic function.

Bicuspid aortic valve with associated aortopathy, significant left ventricular hypertrophy or concomitant hypertrophic cardiomyopathy: A diagnostic and therapeutic challenge

Due to its prevalence of 0.5%to 2%in the general population,with a 75%predominance among men,bicuspid aortic valve is the most common congenital heart defect.It is frequently accompanied by other cardiac congenital anomalies,and clinical presentation can vary significantly,with stenosis being the most common manifestation,often resulting in mild to moderate concentric hypertrophy of the left ventricle.Echocardiography is the primary diagnostic modality utilized for establishing the diagnosis,and it is often the sole diagnostic tool relied upon by clinicians.However,due to the heterogeneous clinical presentation and possible associated anomalies(which are often overlooked in clinical practice),it is necessary to employ various diagnostic methods and persist in finding the accurate diagnosis if multiple inconsistencies exist.By employing this approach,we can effectively manage these patients and provide them with appropriate treatment.Through a clinical case from our practice,we provide an overview of the literature on bicuspid aortic valve with aortophaty and the possible association with hypertrophic cardiomyopathy,diagnostic methods,and treatment options.This review article highlights the critical significance of achieving an accurate diagnosis in patients with bicuspid aortic valve and significant left ventricular hypertrophy.It is crucial to exclude other possible causes of left ventricular outflow tract obstruction,such as sub-or supra-aortic obstructions,and hypertrophic cardiomyopathy.

Circular RNA circ_0003609 ameliorates hypertrophied ligamentum flavum by regulating the miR-155/SIRT1 axis

Background:Hypertrophy of the ligamentumflavum(HLF)is a common contributor to spinal stenosis which results in significant neurological impairments.Circular RNA(circRNA)circ_0003609 has been linked to HLF;however,the exact mechanism by which it causes this disease is unclear.Methods:Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference.Cell proliferation andfibrosis-related gene expression were checked by the Cell Counting Kit-8(CCK-8)assay and western blotting.CircBank’s prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment.The function of the miR-155/sirtuin 1(SIRT1)axis in controlling HLFfibrosis was further examined.Results:Overexpression of circ_0003609 suppressed HLF cell propagation andfibrosis compared to its silencing.It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled thefibrosis of HLF cells.It was found that circ_0003609 acted as a sponge for miR-155,regulating thefibrosis of HLF cells.Further,miR-155 targets SIRT1,and the miR-155/SIRT1 axis promotes HLF cellfibrosis.Conclusion:Circ_0003609 ameliorates hypertrophied ligamentumflavum(LF)by modulating the miR-155/SIRT1 axis,indicating a potential treatment approach for HLF.

Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy:Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits

Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and mechanisms of the essential oil,the main active ingredient of Cymbopogon citratus,on isoproterenol(ISO)-induced cardiomyocyte hypertrophy.Methods:The compositions of Cymbopogon citratus essential oil(CCEO)were determined by gas chromatography-mass spectrometry.Cardiomyocytes were pretreated with 16.9µg/L CCEO for 1 h followed by 10µmol/L ISO for 24 h.Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated.Subsequently,transcriptome sequencing(RNA-seq)and target verification were used to further explore the underlying mechanism.Results:Our results showed that the CCEO mainly included citronellal(45.66%),geraniol(23.32%),and citronellol(10.37%).CCEO inhibited ISO-induced increases in cell surface area and protein content,as well as the upregulation of fetal gene expression.Moreover,CCEO inhibited ISO-induced NLRP3 inflammasome expression,as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3,ASC,CASP1,GSDMD,and IL-1β,as well as reduced protein levels of NLRP3,ASC,pro-caspase-1,caspase-1(p20),GSDMD-FL,GSDMD-N,and pro-IL-1β.The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes.Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1,Sdhd,mt-Cytb,Uqcrq,and mt-Atp6 but had no obvious effects on mt-Col expression.Conclusion:CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

Hypertrophic cardiomyopathy and left ventricular non-compaction:Distinct diseases or variant phenotypes of a single condition?

Hypertrophic cardiomyopathy(HCM)is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle(LV)wall that cannot be solely attributed to abnormal loading conditions.HCM may present with an intraventricular or LV outflow tract obstruction,diastolic dysfunction,myocardial fibrosis and/or ventricular arrhythmias.Differentiating HCM from other diseases associated with LV hypertrophy,such as hypertension,aortic stenosis,or LV non-compaction(LVNC),can at times be challenging.LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae,often accompanied by increased LV myocardial mass.Previous studies indicate that the LVNC phenotype may be observed in up to 5%of the general population;however,in most cases,it is a benign finding with no impact on clinical outcomes.Nevertheless,LVNC can occasionally lead to LV systolic dysfunction,manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy,with an increased risk of thrombus formation and arterial embolism.In extreme cases,where LVNC is associated with a very thickened LV wall,it can even mimic HCM.There is growing evidence of an overlap between HCM and LVNC,including similar genetic mutations and clinical presentations.This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are,in fact,two distinct entities.

Left ventricular regional and global diastolic function assessed using Quantitative Tissue velocity Imaging in patients with hypertrophic cardiomyopathy

Objectives The study was performed to assess the left ventricular (LV) regional and global diastolic function、left ventricular wall motion features in patients with Hypertrophic cardiomyopathy by Quantitative Tissue Velocity Imaging (QTVI). Methods 42 patients with hypertrophic cardiomyopathy and 36 age-matched normal subjects underwent QTVI study. Off-line LV regional muscular tissue velocity Imaging along LV apical long-axis view were obtained. Regional diastolic function was assessed in using peak tissue velocities of LV regional muscular tissue during early diastole (Ve)and LA contraction (Va), Ve/Va ratio, derived from Tissue Velocity Imaging. Global diastolic function was reflected by isovolumic relaxation time(IRT) and mitral valve peak flow velocity ( E/A ) calculated with pulsed wave doppler. The end-diastolic interventricular septal thickness (ⅣSt) was measured by conventional 2 - dimension echocardiography. Results ① Ve、 Va、 Ve/Va in the segments of hypertrophic interventricular septum (IVS) reduced wlhile E/A ratio significantly reduced and IRT markedly prolonged in HCM patients than in normal subjects。 ② Ve、 Ve/Va were significant reduced in the segments of hypertrophic interventricular septum compared with other LV segments in HCM patients . ③ There was a correlation between Ve/Va and E/A in HCM patients with abnormal E/A ratio (r = 0. 70). ④ There was a negative correlation between Ve/Va and ⅣSt in non -obstruction HCM patients (B group , r = -0.61 ) Conclusions QTVI offers a newer method in clinical practice which has a higher sensibility and accuracy in evaluating the LV regional and global diastolic function in HCM patients .

Plasma Norepinephrine and Hemorheology in Essential Hypertensive Patients with Different Patterns of Left Ventricular Hypertrophy

对80例不同类型高血压左室肥厚（LVH）患者的血浆去甲肾上腺素（NE）和血液流变学改变进行观察。结果显示，（1）向心性肥厚组（CH）高切变率下全血粘度（WBV230）显著升高；（2）不对称性室间隔肥厚组（ASH）血浆NE和收缩末期室壁应力（ESS）增高较明显；（3）多元回归分析显示，SBP，ESS和血浆NE是影响相对室壁厚度的重要因素。提示CH是一种对压力负荷过重而产生的代偿形式；ASH的形成除了负荷因素外血浆NE可能起更重要的作用。

甲基化测序和转录组整合分析黄韧带肥厚的分子机制

背景:黄韧带肥厚是腰椎管狭窄症的最主要病因,是多个病理因素共同作用的结果,目前黄韧带肥厚的分子机制、作用通路尚不明确,缺乏有效的非手术治疗方案。目的:使用甲基化测序和转录组整合分析方法,研究黄韧带肥厚发生发展的分子机制。方法:收集5个正常黄韧带组织和5个肥厚黄韧带组织,采用甲基化测序记录异常甲基化位点和甲基化状态,采用转录组整合分析记录异常表达的基因,取二者交集中甲基化水平与表达水平负相关的基因。采用GO和KEGG富集分析研究差异基因表达的主要功能通路和分子功能。使用PPI互作分析筛选调控黄韧带肥厚的关键基因。结果与结论:对两组黄韧带行甲基化测序发现高甲基化位点37173个,低甲基化位点10583个,转录组整合分析发现异常表达基因720个,其中463个上调基因、257个下调基因。两者重叠基因383个,其中192个基因甲基化水平与表达水平负相关。GO功能通路分析结果显示分子功能富集到10个条目,细胞组分富集到15个条目,生物学途径富集到30个条目。KEGG通路富集分析结果显示,192个基因主要富集到PI3K-Akt信号通路、Rap1信号通路、Focal adhesion信号通路、信号通路等9条通路。PPI互作分析筛选出PPARG、EGFR、CNR1、TNF和COL11A25个基因可能是调控黄韧带肥厚的关键基因,主要通过调控组织纤维化、细胞增殖分化、炎症因子水平、胶原纤维表达水平等途径影响黄韧带肥厚的发生发展。

Expression of Wnt and NCX1 and its correlation with cardiomyocyte apoptosis in mouse with myocardial hypertrophy

Objective:To study the correlation between expression of Wnt and NCXl and cardiomyocyte apoptosis in mouse with myocardial hypertrophy.Methods:C57B/16 male mice were given the subcutaneous injection of 1 mg/kg isoprenaline to build the myocardial hypertrophy model.After 14 d of model building,mice were executed by cervical vertebra luxation.The ratio of heart weight/body weight(HW/BW) and heart weight/tibia length(HW/TL) was observed and proved using HE staining mat detected the size of eaidiomyocytes.40 male C57B/16 mice were randomly divided into the sham group(normal saline) and model group(isoprenaline),with 20 mice in each group.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was applied to detect the cardiomyocyte apoptosis;while Western blot and immunohistochemistry were employed to detect the expression of Wnt and NCX1.Meanwhile,the correlation between these two proteins and cardiomyocyte apoptosis was explored.Results:Compared with the sham group,the ratio of HW/BW and HW/TL was increased in the model group,as well as the bigger and hypertrophied cardiomyocytes,decreased number and increased apoptosis of eaidiomyocytes,and increased positive expression of Wnt3 a,WntSa and NCXl in the cardiac muscle tissue.Besides,there was positive correlation between the expression of Wnt and NCXl and the cardiomyocyte apoptosis.Conclusions:The expression of Wnt3 a,Wnt5a and NCXl in mouse with myocardial hypertrophy is increased and positively correlated with the cardiomyocyte apoptosis.

The Effect of TanshinoneⅡ A upon the TGF-beta1/Smads Signaling Pathway in Hypertrophic Myocardium of Hypertensive Rats

To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with high-dose TSN Ⅱ A was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN ⅡA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.

Changes of c-fos and c-jun mRNA Expression in Angiotensin Ⅱ-induced Cardiomyocyte Hypertrophy and Effects of Sodium Tanshinone ⅡA Sulfonate

The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction （RT-PCR）. It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly （P〈0.01）. After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group （P〈0.01）. After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group （P〈0.05）. After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ （P〈0.05 or P〈0.01）. It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.

Left ventricular hypertrophy amplifies the QT,and Tp-e intervals and the Tp-e/QT ratio of left chest ECG

Objective： To evaluate the changes in Tp-e interval （an interval from the peak to the end of the T wave）, QT interval and Tp-e/QT ratio of the body surface ECG in patients with left ventricular hypertrophy （LVH）. Methods： The Tp-e interval and QT interval were measured on body surface ECGs in 42 patients without either hypertension or LVH （control group）, 41 patients having hypertension but not LVH （non-LVH group）, and 38 patients with both hypertension and LVH （LVH group）. Results： The mean corrected QT （QTc） interval, and mean corrected Tp-e[T（p-e）c] interval were significantly longer in the LVH group （0.430±0.021s vs. 0.409±0.019s, p 〈 0.01; 0.098±0.013s vs. 0.088±0.011s, respectively） than those in the control group. The Tp-e/QT ratio was also amplified in LVH group （0.232± 0.028 vs.0.218± 0.027） （p 〈 0.05）. Conclusion： LVH increased the QT interval, Tp-e interval and Tp-e/QT ratio of the body surface ECG.

Detection of Left Ventricular Regional Relaxation Abnormalities in Patients with Hypertrophic Cardiomyopathy by Quantitative Tissue Velocity Imaging

To assess the left ventricular regional relaxation abnormalities in patients with hypertrophic cardiomyopathy (HCM) by quantitative tissue velocity imaging (QTVI), Doppler echocardiography and QTVI were performed in HCM (n=10) and healthy subjects (n=11) at apical long-axis, two-chamber and four-chamber views. Regional early diastolic velocity (rVe) and regional atrial contraction (rVa) were measured at each segment of ventricular middle, basal and annular levels. Mean rVe and mean rVa at three levels as well as mean rVe/rVa ratio were calculated. Our results showed that transmitral inflow peak velocities during early diastole (E) and atrial contraction (A) were also measured and E/A ratio was calculated. The rVe of all left ventricular segments in HCM were lower than those in healthy subjects (P<0.05), but compared with healthy subjects majority of rVa in HCM were not different except inferior wall and anterior wall. E between HCM and healthy subjects was different (P=0.036), while mean rVe between them was significantly different (P<0.0001). Mean rVa and mean rVe/rVa of three levels were lower in HCM than in healthy subjects (P<0.05), but there were no differences in A and E/A between them (P=0.22, P=0.101). Left ventricular regional myocardial relaxation is reduced in HCM. Transmitral inflow E and A are influenced by preload, relaxation of myocardium and atrial contraction, etc., while rVe and rVa reflect myocardial relaxation function independently. QTVI is more sensitive and more accurate than conventional Doppler imaging for characterizingregional diastolic properties in HCM.

Association of asymptomatic otitis media with effusion in patients with adenoid hypertrophy

Objective: Clinical symptoms of otitis media with effusion are rarely brought forward to the guardians of young children who the disease is most prevalent in. This often leads to poor scholastic performances and difficult social interactions. The objective of this study was to identify asymptomatic cases of otitis media with effusion present in individuals with adenoid hypertrophy. Material and Methods: In a cross sectional study advocated in Justice K.S.Hegde Hospital, Karnataka India we evaluated one hundred patients above the age of three from August 2016 to December 2017. Candidates who presented with an adenoid nasopharyngeal ratio of more than 0.5 were selected for the study. Individuals who complained of otological symptoms were not considered for the study. Patients cleared of other pathological otological conditions were underwent audiological evaluation with pure tone audiometry and tympanometry for evaluating the middle ear status and hearing loss. Results: The study showed a total of 36% of patients evaluated presented with asymptomatic otitis media with effusion. In candidates who presented with a bilateral B tympanogram, 40% had significant conductive hearing loss of more than 25dB. Conclusion: An objective test such as impedance audiometry in all patients with adenoid hypertrophy would aid in the diagnosis of fluid in the middle ear, so that timely intervention can be done and possible complications be averted.

Hypertrophic cardiornyopathy: from gene defect to clinical disease

Major advances have been made over the last decade in our understanding of the molecular basis ofseveral cardiac conditions. Hypertrophic cardiomyopathy (HCM) was the first cardiac disorder in whicha genetic basis was identified and as such, has acted as a paradigm for the study of an inherited cardiacdisorder. HCM can result in clinical symptoms ranging from no symptoms to severe heart failure andpremature sudden death. HCM is the commonest cause of sudden death in those aged less than 35 years,including competitive athletes. At least ten genes have now been identified, defects in which cause HCM.All of these genes encode proteins which comprise the basic contractile unit of the heart, i.e. the sarcomere.While much is now known about which genes cause disease and the various clinical presentations, very littleis known about how these gene defects cause disease, and what factors modify the expression of the mutantgenes. Studies in both cell culture and animal models of HCM are now beginning to shed light on thesignalling pathways involved in HCM, and the role of both environmental and genetic modifying factors.Understanding these mechanisms will ultimately improve our knowledge of the basic biology of heart musclefunction, and will therefore provide new avenues for treating cardiovascular disease in man.

Nardosinone Protects H9c2 Cardiac Cells from Angiotensin Ⅱ-induced Hypertrophy

Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots ofNardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on Ang Ⅱ-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosi- none （25, 50, 100, and 200μmol/L） or Ang Ⅱ （1 μmol/L）. Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by Ang Ⅱ. The mRNA expression of ANP, BNP and 13-MHC was obviously elevated in Ang Ⅱ-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang Ⅱ-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.

p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in gp130-mediated hypertrophic ventricular myocytes

Objective:To understand the role of ANP mRNA transcription regulation in gpl30-mediated cardiomyocyte hypertrophy,and the involved mitogen-aetivated protein kinase kinase(MEK)-extracellular signal-regulated kinase(ERK,also called p42/p44 MAPK)signaling pathway.Methods:isolated neonatal ventricular myocytes were treated with different concentrations of CT-1(10^(-9),10^(-8)and 10^(-7)mol/L).MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in eardiomyocyte.To inhibit p42/p44 MAPK activity in hypertrophic cardiomyoeytes,the cells were pretreated with a specific MEKI inhibitor.Results:CT-1significantly induced ANP mRNA expression and the viability of canliomyocytes in a doseand time-dependent manner.Furthermore,blocking p42/p44 MAPK activity by the special MEk1 inhibitor uprcgulatcd the ANP mKNA.Conclusions:p42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gpl30-mediated hypertrophic ventricular myocytes.

Effect of matrine and carvedilol on collagen and MMPs activity of hypertrophy myocardium induced by pressure overload

Objective： To explore the effect and mechanism of matrine （Mt.） on myocardial interstitial fibrosis induced by pressure overload. Methods： Pressure overloaded myocardial hypertrophy was produced by banding of aorta abdominalis in 67 male Sprague-Dawley rats weighing （200±15） g. The rats were assigned into one of the following groups： sham-operation control, operation control, operation group treated with matrine （15 mg/（kg·d）） and treated with carvedilol （Car.） （3.6 mg/（kg·d）） group. The rats were given drugs one day after operation. Five weeks after treatment, the left ventricular weight （LVW） was measured and the volume of myocardial cells was detected with Hematoxylin-Eosin （H-E） stain and Masson stain was used to assess the level of fibrosis of the myocardial matrix. Myocardial metalloproteinase activity was quantified with zymography, and survival rate was calculated. Results： Survival rate significantly decreased （P〈0.05）, LVW/BW （body weight）, MMP-2 （matrix metalloproteinase-2） activity （P〈0.05）, size of cardiomyocytes and interstitial fibrosis obviously increased in the operation group compared with sham control group. Mr. and Car. treatment can significantly increase survival rate （P〈0.05）, decrease LVW/BW （P〈0.05） and MMP-2 activity （P〈0.05）, decrease size of cardiomyocytes and interstitial fibrosis compared with operation group. But there was difference compared with sham group. Conclusion： Matrine was shown to be able to prevent cardiac remodelling of bypertrophy cardium induced by pressure overload including myocardial hypertrophy and fibrosis which may be associated with the decrease in MMP-2 activity of heart.

Contra-lateral liver lobe hypertrophy after unilobar Y90 radioembolization:An alternative to portal vein embolization?

Liver resection(LR) with negative margins confers survival advantage in many patients with hepatic malignancies.However,an adequate future liver remnant(FLR) is imperative for safe LR.Presently,in patients with an inadequate FLR; the 2 most established clinical techniques performed to induce liver hypertrophy are portal vein embolization(PVE) and portal vein ligation.More recently,it has been observed that patients who undergo treatment via Y90 radioembolization experience hypertrophy of the contra-lateral untreated liver lobe.Based on these observations,several investigators have proposed the potential use of this modality as an alternative technique for increasing the FLR prior to liver resection.Y90 radioembolization induces hypertrophy at a slower rate than PVE but has the added advantage of concomitant local disease control and tumour downstaging.

DMP1 prevents osteocyte alterations,FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease

During chronic kidney disease (CKD),alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular mortality.The osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization,but its effects in CKD are unknown.We tested the hypothesis that DMP1 supplementation in CKD would improve bone health,prevent FGF23 elevations and minimize consequent adverse cardiovascular outcomes.We investigated DMP1 regulation and effects in wild-type (WT) mice and the Col4a3^-/- mouse model of CKD.Col4a3^-/- mice demonstrated impaired kidney function,reduced bone DMP1 expression,reduced bone mass,altered osteocyte morphology and connectivity,increased osteocyte apoptosis,increased serum FGF23,hyperphosphatemia,left ventricular hypertrophy (LVH),and reduced survival.Genetic or pharmacological supplementation of DMP1 in Col4a3^-/- mice prevented osteocyte apoptosis,preserved osteocyte networks,corrected bone mass,partially lowered FGF23 levels by attenuating NFAT-induced FGF23 transcription,and further increased serum phosphate.Despite impaired kidney function and worsened hyperphosphatemia,DMP1 prevented development of LVH and improved Col4a3^-/- survival.Our data suggest that CKD reduces DMP1 expression,whereas its restoration represents a potential therapeutic approach to lower FGF23 and improve bone and cardiac health in CKD.