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.

L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenol-induced cardiac hypertrophy

Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.

Ascending aorta dilatation reduces the influence of elevated pulse pressure on left ventricular hypertrophy:findings from a Chinese elderly hypertensive population

OBJECTIVE To determine the role of ascending aorta dilatation in the relationship between pulse pressure(PP)and left ventricular(LV)hypertrophy.METHODS A total of 1556 Chinese elderly hypertensive patients were retrospectively studied.Transthoracic echocardiography was used to obtain the aortic and cardiac structure measurements.In addition,brachial blood pressure was measured,and total arterial compliance,systemic vascular resistance,arterial elastance,and end-systolic LV elastance were calculated.The participants were divided into four groups according to the status of ascending aortic diameter and PP.RESULTS LV mass index increased in succession in the four groups,i.e.,the group with the normal aorta and lower PP,with the normal aorta and higher PP,with aortic dilatation and lower PP,and with aortic dilatation and higher PP(Ptrend<0.001).Total arterial compliance−1,arterial elastance,and end-systolic LV elastance were slightly higher in the individuals with normal aorta compared to those with aortic dilatation,regardless of PP being lower or higher(P<0.01).Compared to the group with the normal aorta and lower PP,individuals with aortic dilatation had a significantly increased multivariable adjusted risk of LV hypertrophy,and higher PP further exacerbated this risk[aortic dilatation with lower PP(OR=1.75,95%CI:1.01–3.04)and aortic dilatation with higher PP(OR=3.42,95%CI:2.03–5.77)].In the relation between PP and LV mass index(β=0.095,P<0.001),-41.3%of the total effect was attributable to mediation by ascending aortic diameter(P<0.0001).CONCLUSIONS In Chinese elderly patients with hypertension,ascending aorta dilatation could reduce the influence of elevated PP on LV hypertrophy.

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.

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.

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.

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.

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.

Effect of Salvia Miltiorrhiza on Left Ventricular Hypertrophy and Cardiac Aldosterone in Spontaneously Hypertensive Rats

Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy (L VH) and its possible mechanism- inhibiting the action of cardiac aldosterone in spontaneously hypertensive rats (SHR) were investigated.Normotensive Wistar- kyoto (WKY ) rats and SHRs were used.Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks.Systolic blood pres- sure (SBP) and left ventricular mass index were measured.Sections of heart tissue were stained with HE method and Van Gieson method.Collagen volume fraction was determined in the leftven- tricle by automatically quantitative m orphometry.Cardiac aldosterone concentration was measured by radioimm unoassay.The results indicated thatcom pared with WKY rats,SHRs exhibited high- er SBP,left ventricular collagen volume fraction,and aldosterone concentration (all P<0 .0 5 ) . After the treatm ent with Salvia Miltiorrhiza,SBP,left ventricular collagen volum e fraction,and aldosterone concentration in SHR were decreased as compared with control group (P<0 .0 5 ) ex- cept SBP.It was concluded thatchronic treatment with Salvia Miltiorrhiza could preventleftven- tricular hypertrophy in SHR,significantly inhibit collagen compositions in left ventricle.The m echanism was probably related with the inhibition of the cardiac aldosterone action.

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.

Improved scoring system for the electrocardiographic diagnosis of left ventricular hypertrophy

BACKGROUND Left ventricular hypertrophy(LVH) is a common manifestation of cardiovascular disease and a risk factor for cardiovascular morbidity and mortality, but available methods for its electrocardiographic(ECG) diagnosis have limited accuracy.AIM To investigate findings associated with LVH on ECG and developed an improved system for the diagnosis of LVH.METHODS A cohort study comparing ECG data acquired within 30 days of transthoracic echocardiography(TTE) was performed. Multivariate regression analysis identified ECG findings associated with increased LV mass and mass index. A scoring system was derived and performance compared to established criteria for LVH.RESULTS Data from 5486 outpatients with TTEs and corresponding ECGs were included in the derivation cohort, 333(6.1%) of whom had LVH by TTE. In the primary regression analysis, findings associated with LVH were amplitudes of Q in V3, R in V6, S in V3, T in V6, P' in V1, P in V6, as well as R and T-axis discordance, R peak time in V6, QRS duration, weight, height, sex, and age. From this we derived a score consisting of 5 criteria, and validated it in an independent cohort of 910 patients. With a threshold of 1.5 points, sensitivity and specificity were67.9% and 81.4%, and 62.5% and 83.2% in the derivation and validation cohorts,respectively. With a threshold of 2 points, sensitivity and specificity were 42.3% and 93.0%, and 37.5% and 93.4% in these cohorts.CONCLUSIONS This score had superior sensitivity for detection of LVH by ECG while making a modest sacrifice in specificity compared to conventional criteria.

Effect of hepatic artery embolization on liver hypertrophy response in a rabbit liver VX2tumor model

BACKGROUND:Portal vein embolization not only induces hypertrophy of the non-embolized liver,but also enhances tumor growth.The latter could be prevented by embolizing the hepatic arteries supplying the tumor-bearing liver segments.This study aimed to determine the effects of transcatheter arterial embolization(TAE)on tumor volume and liver regeneration in a rabbit VX2 tumor model.METHODS:Twenty-three rabbits underwent subcapsular tumor implantation with a VX2 tumor.Two weeks after implantation,18 rabbits were used for TAE experiments,5were for sham controls.Tumor response and liver regeneration response of the embolized cranial and non-embolized caudal liver lobes were assessed by CT volumetry,liver to body weight index,and the amount of proliferating hepatocytes.RESULTS:All super-selective arterial tumor embolization procedures were performed successfully.Despite embolization,the tumor volume increased after an initial steady state.The tumor volume after embolization was smaller than that of the sham group,but this difference was not significant.Massive necrosis of the tumor,however,was seen after embolization,without damage of the surrounding liver parenchyma.There was a significant atrophy response of the tumor bearing cranial lobe after super-selective arterial embolization of the tumor with a concomitant hypertrophy response of the non-embolized,caudal lobe.This regeneration response was confirmed histologically by a significantly higher number of proliferating hepatocytes on the Ki-67 stained slides.CONCLUSIONS:Super-selective,bland arterial coil embolization causes massive necrosis of the tumor,despite increase of volume on CT scan.Atrophy of the tumor bearing liver lobe is seen after arterial embolization of the tumor with a concomitant hypertrophy response of the non-embolized lobe,despite absence of histological damage of the tumor-surrounding liver parenchyma.

Effect of Xinjikang on left ventricular hypertrophy remodeling in hypertensive rats

Objective:To investigate the effects of Xinjikang on the left ventricular hypertrophy remodeling and myocardial activity in hypertension.Methods:Sixty Wistar rats were randomly divided into four groups.The pressure-loaded left ventricular hypertrophy model was established with abdominal aorta ligation method.Rats in A and B groups were intragastrically administered with physiological saline,while C and D groups were administered with Xinjikang and metoprolol,respectively.The changes in blood pressure.E/A ratio,myocardial pathological morphology,myocardial lipoperoxides and superoxide dismustase activity in four groups were observed and compared before and after treatment.Results:There were statistically significant differences in E/A ratio between C group after treatment and model group(P<0.05).while no difference was observed between A and D groups(P>0.05);after treatment the myocardial lipoperoxides and superoxide dismustase contents in C and D groups were improved significantly compared with model group(P<0.05).Conclusions:Xinjikang can improve myocardial injury,restore myocardial parenchyma and myocardial interstitial remodeling functions in hypertensive rats with the left ventricular hypertrophy.

Effect of Salvia Miltiorrhiza Bge on Left Ventricular Hypertrophy and the Expression of Tumor Necrosis Factor-α in Spontaneously Hypertensive Rats

The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circum- ferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.

Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection

To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss.METHODSThe ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH.RESULTSLiver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration.CONCLUSIONHyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

Muscle hypertrophy in transgenic mice due to over-expression of porcine myostatin mutated at its cleavage site

Myostatin, a member of the transforming growth factor beta（TGF-β） superfamily, is a dominant inhibitor that acts to limit skeletal muscle growth and development. In this study, we generated transgenic mice that express porcine myostatin containg mutations at its cleavage site（RSRR） to evaluate its effect on muscle mass. Results showed that the weight of four skeletal muscles including gastrocnemius, rectus femoris, tibialis anterior, and pectoralis increased by 17.83 and 28.39%, 21.76 and 28.70%, 34.31 and 41.62%, 53.21 and 27.54% in transgenic male and female mice, respectively, compared to their corresponding non-transgenic control mice. Measurement of muscle fiber size and number indicated that the mean myofiber size increased by 50.73 and 61.30% in transgenic male and female mice respectively compared to the non-transgenic controls. However, there was no difference in the number of myofiber between transgenic and non-transgenic male mice. These results clearly demonstrated that the increase in skeletal muscle mass in transgenic mice is caused by hypertrophy instead of hyperplasia.

Alterations in Cardiac Structure and Function in a Modified Rat Model of Myocardial Hypertrophy

This study was aimed to establish a stable animal model of left ventricular hypertrophy （LVH） to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats （80-100 g） was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide （BNP） measurement at 3, 4 and 6 weeks after abdominal aortic constriction （AAC）. The results showed that the acute mortality rate （within 24 h） of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal （IVS）, LV posterior wall （LVPWd）, LV mass index （LVMI）, cross-sectional area （CSA） of myocytes, and perivascular fibrosis; the ejection fraction （EF）, fractional shortening （FS）, and cardiac output （CO） were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.