Relationship between lipidslevelsand right ventricular volume overload in congestive heart failure

BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol（TCL）, high-density lipoprotein cholesterol（HDL-C）, low-density lipoprotein cholesterol（LDL-C）, and triglycerides（TG）]and right ventricle end diastolic diameter （RVEDD）, left ventricle end diastolic diameter （LVEDD）, right atrium diameter （RA）, left atrium diameter （LA）, or left ventricle ejection fraction （LVEF） were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD （r=-0.34,P〈0.001） and RA （r=-0.36,P〈0.001）. Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.

Transformation of myocardial energy metabolism pattern during myocardial remodeling caused by volume overload

Objective To elucidate the transformation of energy metabolism patterns in the process of myocardial remodeling induced by volumeoverload and to explore a novel intervention target for the prevention,delay or even reversal of structural heart dysfunction.Methods Thirty C57/BL6 mice,20-30 g,half male and half female,were randomly divided into model group(n=15)and sham operation group(n=15).Each group was divided into subacute phase(2 weeks after surgery,n=5),cardiac functional compensation phase(5 weeks after surgery,n=5)and decompensation phase(15 weeks after surgery,n=5).

VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYPERTROPHY

Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expression on the model of rat cardiac volume-overload hypertrophy was examined by immunohistochemical study. Results The immunohistochemical study indicated the expression of c-myc protein was increased obviously at 4-6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-overload, then decreased gradually along with development of volume-overload hypertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on,c-myc gene and the product of it do not act anymore;While it may be that c-myc gene and the product of it increased following with myocardial hypertrophy, and have not direct relation to the occurrence and development of myocardial hypertrophy.

Effects of combination of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca^(2+)-ATPase activity in rat cardiac pressure-overload hypertrophy

Aim： To observe effects of angiotensin （Ang） II receptor antagonist （ATI） irbesartan and angiotensin-converting enzyme （ACE） inhibitor perindopril on rat myocardium calcineurin expression and sarcoplasmic reticulum Ca^2＋-ATPase activity in the model of pressure-overload cardiac hypertrophy. Methods： Forty male adult Sprague Dawley rats were divided into 5 groups One group was treated by sham operation; four groups were myocardium hypertrophy cases caused by banding aortic above renal artery. Drugs were given one week after operation. Group 1： sham group, rats （n=8） were gavaged with normal saline 2 ml/（kg·d） （ig）; Group 2： control group, rats （n=8） were treated with normal saline 2 ml/（kg·d） （ig）; Group 3： rats （n=8） were given perindopril 2 mg/（kg·d） （ig）; Group 4： rats （n=8） were treated with irbesartan 20 mg/（kg·d） （ig）; Group 5： rats （n=8） were given irbesartan 20 mg/（kg·d） plus perindopril 2 mg/（kg·d） （ig）. Morphometric determination, calcineurin expression and sarcoplasmic reticulum Ca^2＋-ATPase activity were done at the end of 6 week of drug intervention. Expression of calcineurin in myocardium was detected by immunohistochemistry. Results： Left ventricular mass index （LVMI）, transverse diameter of myocardial cell （TDM）, calcineurin activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination drug therapy group. Sarcoplasmic reticulum Ca^2＋-ATPase activity was increased after drug intervention, especially in the combined drug therapy group. Calcineurin expression in myocardium was remarkably decreased after drug intervention. LVMI was positively correlated with TDM and calcineurin, negatively correlated with sarcoplasmic reticulum Ca^2＋-ATPase. Conclusion： These data suggest that irbesartan and perindopril inhibit cardiac hypertrophy through the increased activity of sarcoplasmic reticulum Ca^2＋-ATPase and decreased expression of calcineurin. Their combination had better effects on regressing of ventricular hypertrophy.

Effect of Zhenwu Tang Granule on pressure-overloaded left ventricular myocardial hypertrophy in rats

BACKGROUND： In the perspective of traditional Chinese medicine, few studies have focused on the compound preparations though there are many investigations. The present study was undertaken to investigate the effect of Zhenwu Tang Granule on chronic pressure-overloaded left ventricular hypertrophy in rats.METHODS： The study was performed at the laboratory of Guangzhou Institute of Respiratory Disease. Male SD rats were divided randomly into 3 groups： sham operation group （n=8）, operation group （n=15） and traditional Chinese medicine （TCM） group （n=15）.The model of myocardial hypertrophy was made by gradually constricting the abdominal aorta. Sixteen weeks later, cardiac ultrasonography was performed in all groups in order to ascertain post-operational left ventricular （LV） hypertrophy. And Zhenwu Tang Granule was added at a dose of 12 g/kg in the mixed feedstuff for 8 weeks in the TCM group. In the 24th week, weight, structure as well as function of the heart in each group were measured by high-frequency ultrasonography, and Masson＇s staining was performed on the cardiac muscles. Meanwhile, total collagen volume fraction （CVF-T） and non-coronary vessel collagen volume fraction （CVF-NV） were analyzed.RESULTS： There was an increase in the weight of the heart in the operation group, with the left ventricule dominated （P〈0.05）. The heart was enlarged, with diastolic interventricular septal distance （IVSd） and left ventricular posterior wall distance （LVPWd） dominated （P〈0.01）.There was a significant decrease in the cardiac function （P〈0.05）. The weight （P〈0.01） and volume of the heart decreased in the TCM group compared with the operation group, with IVSd and systolic left ventricular posterior wall dominated （P〈0.01）. And the cardiac function was improved （P〈0.05）. Significant interstitial and collagen hyperplasia was shown in the operation group based on pathological analysis, and various improvements were proved in the TCM group, i.e. there was a significant decrease in CVF-T and CVF-NV （P〈0.01） compared with the operation group; but no difference （P〉0.05） was found when compared with the pseudo-operation group.CONCLUSION： Zhenwu Tang Granule could reduce the weight and volume of the heart, improve the cardiac function, inhibit hyperplasia of collagen, and reverse myocardial hypertrophy in rats with pressure-overloaded left ventricular hypertrophy.

IN PATIENTS WITH HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY AND CORONARY HEART DISEASE,CORONARY FLOW RESERVE IS SIMILARLY IMPAIRED

Coronary blood flow reserve (CFR) was assessed by transesophageal Doppler echocardiography in normal subjects (group A. n=20),hypertensive non-left ventricular hypertrophy (non-LVH)Patients (group B,n=22). hypertensive patients with LVH(group C.n=32)and coronary heart disease patients (group D. n=33) with the volume sample placed at the bifurcation of the left main and left main and left descending coronary artery. Coronary blood flow velocity (CBFV)was evaluated at rest.2 minutes after dipyridamole (0. 56mg/kg. i. v.) . and 2 minutes after aminophylline i.v. The ratio of dipyridamole to rest maximal diastolic velocity (D/R PDV) was considered the index of coronary blood flow reserve.It was found that D/R PDV was significantly less in groups C and D compared with that in groups A and B (D PDC,1.84±0. 57. 1. 57±0. 41 versus 2.59±0.70 and 2.22+0.58,respectively),with no difference in D/R PDV between groups C and D.Twenty-four out of 32 patients in group C with D/R PDV were less than 2.0 compared to 29 out of 33 patients in group D (P>0.05).Significant negative correlation was found between D/R PDV. D/R PSV and interseptal thickness. left ventricular mass index in hypertensive patients.These data show that impaired CFR in hypertensive patients with LVH is comparable to that in patients with coronary heart disease.

Blood pressure circadian rhythm and heart rate turbulence in hypertensive patients: relationship with left ventricular hypertrophy

Objective To investigate the relationship of blood pressure circadian rhythm with myocardial hypertrophy and the changes of autonomic nerve function in patients with essential hypertension (EH). Methods Eighty-two female patients with essential hypertension (EH) underwent 24-hours ambulatory blood pressure monitorings (ABPM), dynamic electrocardiogram (Holter) and echocardiography examination. Patients were classified into non-dipping group (n=40) and dipping group (n=42) according to the result of ABPM. Left ventricular mass index (LVMI), heart rate variability (HRV) in time domain (including SDNN, SDANN, rMSSD, PNN50) and heart rate turbulence (HRT) parameters (including turbulence onset [TO] and turbulence slope [TS]) were measured. Results Compared with those in dipping group, patients in non-dipping group have higher incidence of LVH (19.0% vs 52.5%, P<0.01), greater mean LVMI (112.39±12.79 g/m2 vs 121.98±13.35 g/m2, P<0.01), decreased PNN50 and rMSSD. TS value was decreased while TO was increased in non-dipping group compared with those in dipping group (both P <0.01); patients with LVH showed decreased TS and increased TO, compared with those without LVH. Conclusion In female patients with EH, non-dipping blood pressure circadian is associated with higher incidence of LVH. The HRV and HRT were more remarkably blunted in non-dipping patients, as well as those with LVH.

Ultrasound unveiling:Decoding venous congestion in heart failure for precision management of fluid status

This editorial discusses the manuscript by Di Maria et al,published in the recent issue of the World Journal of Cardiology.We here focus on the still elusive pathophysiological mechanisms underlying cardio-renal syndrome(CRS),despite its high prevalence and the substantial worsening of both kidney function and heart failure.While the measure of right atrial pressure through right cardiac catheterization remains the most accurate albeit invasive and costly procedure,integrating bedside ultrasound into diagnostic protocols may substantially enhance the staging of venous congestion and guide therapeutic decisions.In particular,with the assessment of Doppler patterns across multiple venous districts,the Venous Excess Ultrasound(VExUS)score improves the management of fluid overload and provides insight into the underlying factors contributing to cardio-renal interactions.Integrating specific echocardiographic parameters,particularly those concerning the right heart,may thus improve the VExUS score sensitivity,offering perspective into the nuanced comprehension of cardio-renal dynamics.A multidisciplinary approach that consistently incorporates the use of ultrasound is emerging as a promising advance in the understanding and management of CRS.

Diastolic heart failure in the elderly

Heart failure with preserved left ventricular function is a common problem among elderly patients. Given that diastolic heart failure (DHF) occurs in up to 50% of all heart failure admissions, and that incidence increases with age, knowledge of current recommendations for its diagnosis and treatment are extremely important for the elderly population. Causes of DHF include the aging process itself, hypertension, left ventricular hypertrophy, aortic stenosis, and hypertrophic obstructive cardiomyopathy. The patient with DHF may present with signs and symptoms similar to those observed in systolic heart failure. Treatment goals for the patient with DHF include achieving normal volume status, improving relaxation of the left ventricle, regression of hypertrophy if possible, and management of any co-morbidities that may aggravate the clinical status of patients with DHF. Hopefully, in the future, further data from randomized clinical trials will allow a more defined approach to care in these patients.

Arterial hypertension and electrocardiographic diagnosis of left ventricular hypertension in the group of geriatric patients with coronary heart disease living in the far north

As a result of research, high prevalence of arterial hypertension has been identified in the group of patients with coronary heart disease aged 60 and older. Most often, occurring form of arterial hypertension among geriatric patients is isolated systolic arterial hypertension (ISAH). The comparison of two ethnic groups of the population has showed higher levels of systolic and diastolic blood pressure (SBP and DBP) in the group of patients of non-indigenous nationality, rather than Yakut patients. Correlation was recorded in the group of non-indigenous patients as they age. Significant increase in the level of SBP was identified in the group of senile and long-livers than in the elderly. Detection of ECG signs of LVH showed the lowest specificity of Cornell voltage criterion comparing to Sokolow-Lyon criterion with its more often occurrence. ECG-signs of left ventricle hypertrophy are significantly more often established by Sokolow-Lyon criterion for men, Cornell voltage—for women. Correlation has been found between the presence of LVH and combination of Cornell voltage criterion with both Gubner-Ungerleider and Sokolow-Lyon criteria.

Heart failure in subjects with chronic kidney disease:Best management practices

Renal dysfunction is common in patients with heart failure(HF) and can complicate HF therapy.Treating patients with HF and kidney disease is difficult and requires careful assessment,monitoring and balancing of risk between potential benefits of treatment and adverse impact on renal function.In this review,we address the pathophysiological contexts and management options in this adversarial relation between the heart and the kidney,which exists in a substantial proportion of HF patients.Angiotensin converting enzyme inhibitors and β-blockers are associated with similar reductions in mortality in patients with and without renal insufficiency but usually are less often prescribed in patients with renal insufficiency.Careful monitoring of side effects and renal function should be done in all patients with renal insufficiency and prompt measures should be adopted to prevent further complications.

Regional Heterogeneity in 3D Myocardial Shortening in Hypertensive Left Ventricular Hypertrophy: A Cardiovascular CMR Tagging Substudy to the Life Study

Background: Increased relative wall thickness in hypertensive left ventricular hypertrophy (LVH) has been shown by echocardiography to allow preserved shortening at the endocardium despite depressed LV midwall circumferential shortening (MWCS). Depressed MWCS is an adverse prognostic indicator, but whether this finding reflects reduced global or regional LV myocardial function, as assessed by three-dimensional (3D) myocardial strain, is unknown. Methods and Results: Cardiac Magnetic Resonance (CMR) tissue tagging permits direct evaluation of regional 3D intramyocardial strain, independent of LV geometry. We evaluated 21 hypertensive patients with electrocardiographic LVH in the LIFE study and 8 normal controls using 3D MR tagging and echocardiography. Patients had higher MR LV mass than normals (116 ± 40 versus 63 ± 6 g/m2, P = 0.002). Neither echocardiographic fractional shortening (32 ± 6 versus 33% ± 3%), LVEF (63% versus 64%) or mean end-systolic stress (175 ± 27 versus 146 ± 28 g/cm2) were significantly different, yet global MWCS was decreased by both echocardiography (13.4 ± 2.8 versus 18.2% ± 1.5%, P P P = 0.002) in LVH and greater in lateral and anterior regions versus septal and posterior regions ( P P P 0.60, P = 0.001 for both). Conclusions: In patients with hypertensive LVH, despite normal LV function via echocardiography or CMR, CMR intramyocardial tagging show depressed global MWCS while 3D MR strain revealed marked underlying regional heterogeneity of LV dysfunction.

Left Ventricle Geometry Remolding after Heart Transplantation:A Two-dimensional Ultrasound Study

The function of the transplanted heart will be affected by acute allograft rejection, chronic rejection, high blood pressure and so on, which may induce the reconstruction of the left ventricle and the increase of left ventricular mass （LVM）, and eventually lead to left ventricular hypertrophy that will significantly affect the prognosis of heart transplantation （HT）. The purpose of this study was to dy- namically monitor the changes of left ventricular geometric patterns after HT using two-dimensional echocardiography and to understand the remodeling process and its possible influencing factors. The left ventricular internal diameter, interventricular septal wall thickness, posterior wall thickness at end dias- tole were measured and the relative wall thickness （RWT）, left ventricular mass, left ventricular mass index were calculated respectively in 34 HT patients and 34 healthy volunteers by two-dimensional echocardiography. The type of left ventricular geometry was identified based on the echocardiographic determination of LVM index （LVMI） and RWT. The HT patients were divided into three groups ac- cording to the time length after surgery： A （3 months postoperatively）, B （6 months postoperatively） and C （12 months postoperatively）. We compared the parameters of left ventricle between HT group and normal control group, and explored the risk factors causing the increase of LVM. The results showed that 4 patients （16%） in group A had concentric remodeling. Nine patients （34.62%） in group B had re- construction, including 5 cases of concentric remodeling, 2 cases of concentric hypertrophy and 2 cases of eccentric hypertrophy. The hypertrophy incidence rate was 15.4% in group B. 15 patients （62.5%） had reconstruction in group C, including 9 cases of concentric remodeling, 5 cases of concentric hyper- trophy, and 1 case of eccentric hypertrophy. The prevalence of hypertrophy was 25%. Multivariate analysis showed that hypertension and acute rejection history were the risk factors that resulted in left ventricular hypertrophy. It is concluded that the left ventricular remodeling occurs following cardiac transplantation at an early stage and the incidence of left ventricular hypertrophy increases with survival time. In this study, the one-year prevalence of left ventricular hypertrophy was 25% after surgery. Hy- pertension and acute rejection history are risk factors that can predict the left ventricular hypertrophy.

Effects of hypertonic saline solution on body weight and serum creatinine in patients with acute decompensated heart failure

AIM To test the safety and effectiveness of hypertonic saline solution(HSS + F) as a strategy for weight loss andprevention of further deterioration of renal function.METHODS Patients admitted with acute decompensated heart failure(ADHF) who received HSS + F were included in the study. After a period of a standard ADHF treatment, our patients received an intravenous infusion of furosemide(250 mg) combined with HSS(150 mL of 3% NaCl) twice a day for a mean duration of 2.3 d. Our primary outcomes were weight loss and a change in serum creatinine per day of treatment. The parameters of the period prior to treatment with HSS + F were compared with those of the period with HSS + F. RESULTS A total of 47 patients were included. The mean creatinine on admission was 155 μmol/L ± 65 μmol/L, the ejection fraction was 40% ± 17%. The experimental treatment(HSS + F) resulted in greater weight loss per day of treatment than the standard treatment(-1.4 kg/d ± 1.4 kg/d vs-0.4 kg/d ± 1.0 kg/d, P = 0.0168). Importantly, the change in creatinine was not significantly different.CONCLUSION This study supports the effectiveness of HSS + F on weight loss in patients with ADHF. The safety profile, particularly with regard to renal function, leads us to believe that HSS + F may be a valuable option for those patients presenting with ADHF who do not respond to conventional treatment with intravenous furosemide alone.

Molecular mechanism of carvedilol on attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy

Objective to explore the molecular mechanism of carvedilol effect on fetal energy metabolism during the development of cardiac hypertrophy. Methods Male Wistar rats were divided into the coarctation of abdominal aorta group (CAA), sham operation group (SH), and carvedilol intervention group (CAR+CAA, carvedilol 30mg·kg -1 ·day -1 orally) and carvedilol control group (CAR+SH). Hemodynamics, ventricular remodeling parameters, free fatty acid in blood serum and cardiac myocyte, RT PCR analysis of the expressions of Muscle Carnitine Palmitoyltransferase I (M CPT I) and Medium Chain Acyl CoA Dehydrogenase (MCAD) mRNA were measured in all rats at 16 week after operation. Results Left ventricular hypertrophy occurrd after operation 16 weeks in group of CAA, accompanying with plasma free fatty acids accumulation, and both the levels of M CPT I and MCADmRNA were decreased significantly ( P <0.05). Carvedilol can reduce the left ventricular hypertrophy induced by pressure overload. The gene expressions of rate limiting enzyme(M CPT I) and key enzyme of fatty acid (MCAD) were upregulated in the CAR+CAA group, comparing with CAA group ( P <0.05). There was no statistically significant difference between SH group and CAR + SH group. Pressure overload in CAA rats downregulates the gene expression of rate limiting enzyme and key enzyme of fatty acid oxidation. Conclusions The intervention with carvedilol may attenuates the reversion of the metabolic gene expression back towards fetal type through up regulating the expression of M CPT I and MCADmRNA. Thus, carvedilol may confer cardioprotective effects in heart failure partly by preserving of the normal metabolic gene regulation.

Extracorporeal veno-venous ultrafiltration in congestive heart failure:What’s the state of the art?A mini-review

Hospitalizations for heart failure exceed 1 million per year in both the United States and Europe and more than 90%are due to symptoms and signs of fluid overload.Rates of rehospitalizations or emergency department visit at 60 days are remarkable regardless of whether loop diuretics were administered at low vs high doses or by bolus injection vs continuous infusion.Ultrafiltration(UF)has been considered a promising alternative to stepped diuretic therapy and it consists in the mechanical,adjustable removal of iso-tonic plasma water across a semipermeable membrane with the application of hydrostatic pressure gradient generated by a pump.Fluid removal with ultrafiltration presents several advantages such as elimination of higher amount of sodium with less neurohormonal activation.However,the conflicting results from UF studies highlight that patient selection and fluid removal targets are not completely understood.The best way to assess fluid status and therefore establish the fluid removal target is also still a matter of debate.Herein,we provide an up-to-date systematic review about the role of ultrafiltration among patients with fluid overload and its gaps in daily practice.

Upregulation of Zip14 correlates with induction of endoplasmic reticulum stress(ERS)in hypertrophied hearts of Dahl saltsensitive rats

Zinc is a trace element involved in maintaining cellular structure and function.Although zinc is associated with left ventricular hypertrophy(LVH),there have been few reports on this association.This study aimed to evaluate the correlation between Zip14 and expression of endoplasmic reticulum stress(ERS)associated molecules in hypertrophied hearts of rats.Dahl salt-sensitive rats were fed a high salt diet to establish a left ventricular hypertrophy(LVH)rat model.RT-PCR was used to determine Zip14,activating transcription factor(ATF4),ATF6,x-box-binding protein 1(xBP1),C/EBP homologous protein(CHOP),immunoglobulin-binding protein(BiP)mRNA expression.Western blotting was used to evaluate Zip14,BiP,CHOP,GAPDH expression.Zinc levels were measured by Inductively Coupled Plasma Optical Emission Spectroscopy.The results indicated that compared with the Control group,Zip14 mRNA and protein expression in LVH rat hearts were markedly increased(P<0.01).Zinc content in rat heart tissue was significantly increased in the LVH group compared with the Control group(P<0.05).ATF4,ATF6,xBP1 mRNA expressions were increased in LVH rat hearts compared with Control hearts(P<0.001).Compared with the Control group,CHOP and BiP mRNA and protein expression were markedly increased in LVH rat hearts(P<0.05,P<0.01).Linear regression models showed that Zip14 mRNA expressions were positively correlated with zinc concentration,ATF4 and ATF6 mRNA expressions in Control hearts(P=0.0005,P=0.0052,P=0.0026,respectively)and LVH rat hearts(P<0.0001,P=0.0119,P=0.0033,respectively).In conclusion,upregulation of Zip14 in LVH rat hearts correlated with zinc accumulation and induction of ERS.

Holmes Heart and HIV: A Rare Combination of Two “H”s in a 23-Year-Old Widow

A 23-year-old, lean, scoliotic female presented to our hospital with a history of shortness of breath and cyanosis on exertion. Her 2D echocardiography revealed single left ventricle with both atrio-ventricular valves opening in it. She had normally related great arteries, with severe pulmonary artery hypertension, without pulmonary stenosis. Her blood tests indicated that she was reactive to human immunodeficiency virus (HIV-1). The patients died within 2 months despite treatments with anti-retroviral therapy and decongestive therapy.

Signaling Pathways Involved in Cardiac Hypertrophy

Cardiac hypertrophy is the heart＇s response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy （normal growth） and physiological hypertrophy （growth induced by conditioning）, and maladaptive hypertrophy, physical including pathologic or reactive hypertrophy （growth induced by pathologic stimuli） and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response, including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt （PI3Ks/Akt）, G protein-coupled receptors, small G proteins, MAPK, PKCs, Gp130/STAT3, Na＋/H＋ exchanger, peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

miRNA-208a-3p过表达致慢性心衰大鼠心肌细胞线粒体钙超载和功能障碍的机制研究

目的观察miRNA-208a-3p在慢性心力衰竭大鼠心肌中的表达水平,探讨其在线粒体钙稳态和线粒体功能方面的调节机制。方法35只健康SD大鼠,随机分为模型组(n=20)和对照组(n=15),模型组采用腹主动脉直径缩窄法建立慢性心衰模型,对照组行假手术。通过心功能和组织病理学检测评价模型,测定心肌miR-208a-3p表达,心肌线粒体去乙酰化酶3(SIRT3)蛋白和NADH脱氢酶亚基1(ND1)蛋白表达、线粒体Ca2+水平、心肌细胞活性氧(ROS)生成。结果模型组大鼠心肌miR-208a-3p表达水平显著高于对照组(P<0.05),SIRT3蛋白表达显著低于对照组(P<0.001),且miR-208a-3p与SIRT3表达呈显著负相关;模型组ND1蛋白表达显著低于对照组(P<0.05),且ND1与SIRT3表达呈显著正相关;模型组心肌细胞线粒体内Ca2+水平显著高于对照组(P<0.05),心肌细胞ROS生成也显著高于对照组(P<0.05)。结论慢性心衰心肌组织miR-208a-3p过度表达与SIRT3/ND1活性降低相关,抑制线粒体呼吸链活性,此外,心肌细胞出现线粒体钙超载和ROS生成增加,进一步加剧线粒体呼吸功能障碍,是慢性心衰线粒体功能障碍的重要机制。