Elevation of B-type natriuretic peptide is a sensitive marker of left ventricular diastolic dysfunction in patients with maintenance haemodialysis

Objective: To determine the clinical value of B-type natriuretic peptide (BNP) in diagnosing left ventricular diastolic dysfunction (LVDD) associated with maintenance haemodialysis (MHD) population.

Methods: Plasma BNP was determined in 59 MHD patients with normal ejection fraction. The ratio of early to late annular velocity (E’/A’) was determined by tissue Doppler imaging as a parameter of diastolic function.

Results: LVDD occurred in 66% of the patients. Receiver-operating characteristic curve analyses identified a cut-off of 353.6 pg ml^?1 as the one with the highest sensitivity and specificity for detecting LVDD.

Conclusions: Plasma BNP may serve as a potential biomarker in diagnosing LVDD in MHD patients with normal systolic function.     

A diastolic dysfunction model in non-human primates with transverse aortic constriction

Transverse aortic constriction (TAC) has been widely used to study cardiac hypertrophy, fibrosis, diastolic dysfunction, and heart failure in rodents. Few studies have been reported in preclinical animal models. The similar physiology and anatomy between non-human primates (NHPs) and humans make NHPs valuable models for disease modeling and testing of drugs and devices. In the current study, we aimed to establish a TAC model in NHPs and characterize the structural and functional profiles of the heart after TAC. A non-absorbable suture was placed around the aorta between the brachiocephalic artery and left common carotid artery to create TAC. NHPs were divided into 2 groups according to pressure gradient (PG): the Mild Group (PG=31.01 ± 12.40 mmHg, n=3) and the Moderate Group (PG=53.00 ± 9.37 mmHg, n=4). At 4 weeks after TAC, animals in both TAC groups developed cardiac hypertrophy: enlarged myocytes and increased wall thickness of the left ventricular (LV) anterior wall. Although both TAC groups had normal systolic function that was similar to a Sham Group, the Moderate Group showed diastolic dysfunction that was associated with more severe cardiac fibrosis, as evidenced by a reduced A wave velocity, large E wave velocity/A wave velocity ratio, and short isovolumic relaxation time corrected by heart rate. Furthermore, no LV arrhythmia was observed in either animal group after TAC. A diastolic dysfunction model with cardiac hypertrophy and fibrosis was successfully developed in NHPs.     

Nitric oxide scavenging by cell-free hemoglobin may be a primary factor determining hypertension in polycythemic patients

Abstract

We tested the hypothesis that hypertension associated with polycythemia vera (PV) may be related to hemoglobin released from erythrocytes (cell-free hemoglobin, fHb). We assessed hematocrit, mean arterial pressure (MAP), blood viscosity, and the level of fHb and nitrite/nitrate (NO_x) in the plasma of 73 PV patients and 38 healthy controls. The effect of isovolemic erythrocytapheresis (ECP) on the considered parameters was also studied. From the whole group of PV patients a subset of subjects with normal (normotensive patients, n = 16) and elevated MAP (hypertensive patients, n = 57) can be subtracted.

It was found that in comparison with healthy controls, PV patients have significantly (p ≤ 0.01) elevated Hct (0.567 vs. 0.422), blood viscosity (5.45 vs. 3.56 cP), MAP (106.8 vs. 93.8 mmHg), plasma fHb (9.7 vs. 2.8 mg/dL), and NO_x levels (34.1 vs. 27.5 μM). Compared with normotensive patients, hypertensive PV patients demonstrated a higher rise in fHb (10.2 vs. 8.0) and plasma NO_x levels (35.8 vs. 31.0). In PV patients, fHb positively correlates with MAP (r = 0.489), NO_x levels (r = 0.461), hematocrit (r = 0.428), and viscosity (r = 0.393). Blood viscosity positively correlated with hematocrit (r = 0.894), but not with other considered parameters. In PV patients MAP poorly correlated with hematocrit, whereas the correlation between MAP and NO_x altered from ? 0.325 (healthy control) to + 0.268 (PV patients). ECP procedure was associated with a significant (p < 0.01) reduction of hematocrit, fHb, blood viscosity, and MAP. In the normotensive subgroup of PV patients the ECP procedure did not affect MAP. It can be concluded that accelerated scavenging of nitric oxide by fHb rather than high Hct may be a key factor determining the development of hypertension in PV patients.     

Measuring passive myocardial stiffness in Drosophila melanogaster to investigate diastolic dysfunction

Aging is marked by a decline in LV diastolic function, which encompasses abnormalities in diastolic relaxation, chamber filling and/or passive myocardial stiffness. Genetic tractability and short life span make Drosophila melanogaster an ideal organism to study the effects of aging on heart function, including senescent-associated changes in gene expression and in passive myocardial stiffness. However, use of the Drosophila heart tube to probe deterioration of diastolic performance is subject to at least two challenges: the extent of genetic homology to mammals and the ability to resolve mechanical properties of the bilayered fly heart, which consists of a ventral muscle layer that covers the contractile cardiomyocytes. Here, we argue for widespread use of Drosophila as a novel myocardial aging model by (1) describing diastolic dysfunction in flies, (2) discussing how critical pathways involved in dysfunction are conserved across species and (3) demonstrating the advantage of an atomic force microscopy-based analysis method to measure stiffness of the multilayered Drosophila heart tube versus isolated myocytes from other model systems. By using powerful Drosophila genetic tools, we aim to efficiently alter changes observed in factors that contribute to diastolic dysfunction to understand how one might improve diastolic performance at advanced ages in humans.     

Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging

Objective: This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. Methods: Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image-registration technology. Results: Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08?±?0.044 vs. ?0.031?±?0.077, p?=?0.001) and a reduced strain rate (1.834?±?0.909 vs. 3.791?±?2.394, p?=?0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. Conclusions: The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI.     

Left Ventricular Dysfunction Caused by Unrecognized Surgical AV block in a Patient with a Manifest Right Free Wall Accessory Pathway

A 24-year-old male with Wolff-Parkinson-White syndrome developed systolic cardiomyopathy and severe heart failure following membranous ventricular septal defect repair and tricuspid valve replacement. Following successful catheter ablation of a right anterolateral accessory pathway (AP), complete AV block with junctional escape rhythm was noted. Patient subsequently underwent implantation of a biventricular ICD. Heart failure symptoms significantly improved soon after and left ventricular systolic function normalized 3 months post-procedure. In this case, surgically acquired AV block likely explains development of postoperative cardiomyopathy by facilitating ventricular activation solely via the AP and thereby increasing the degree of ventricular dyssynchrony.     

Matrix metalloproteinase inhibition attenuates right ventricular dysfunction and improves responses to dobutamine during acute pulmonary thromboembolism

Activated matrix metalloproteinases (MMPs) cause cardiomyocyte injury during acute pulmonary thromboembolism (APT). However, the functional consequences of this alteration are not known. We examined whether doxycycline (a MMP inhibitor) improves right ventricle function and the cardiac responses to dobutamine during APT. APT was induced with autologous blood clots (350 mg/kg) in anaesthetized male lambs pre‐treated with doxycycline (Doxy, 10 mg/kg/day, intravenously) or saline. Non‐embolized control lambs received doxycycline pre‐treatment or saline. The responses to intravenous dobutamine (Dob, 1, 5, 10 μg/kg/min.) or saline infusions at 30 and 120 min. after APT induction were evaluated by echocardiography. APT increased mean pulmonary artery pressure and pulmonary vascular resistance index by ~185%. Doxycycline partially prevented APT‐induced pulmonary hypertension (P < 0.05). RV diameter increased in the APT group (from 10.7 ± 0.8 to 18.3 ± 1.6 mm, P < 0.05), but not in the Doxy+APT group (from 13.3 ± 0.9 to 14.4 ± 1.0 mm, P > 0.05). RV dysfunction on stress echocardiography was observed in embolized lambs (APT+Dob group) but not in embolized animals pre‐treated with doxycycline (Doxy+APT+Dob). APT increased MMP‐9 activity, oxidative stress and gelatinolytic activity in the RV. Although doxycycline had no effects on RV MMP‐9 activity, it prevented the increases in RV oxidative stress and gelatinolytic activity (P < 0.05). APT increased serum cardiac troponin I concentrations (P < 0.05), doxycycline partially prevented this alteration (P < 0.05). We found evidence to support that doxycycline prevents RV dysfunction and improves the cardiac responses to dobutamine during APT.     

Senescence marker protein 30 inhibits angiotensin II-induced cardiac hypertrophy and diastolic dysfunction

Background and objective

Senescence marker protein 30 (SMP30) is assumed to behave as an anti-aging factor. Recently, we have demonstrated that deficiency of SMP30 exacerbates angiotensin II-induced cardiac hypertrophy, dysfunction and remodeling, suggesting that SMP30 may have a protective role in the heart. Thus, this study aimed to test the hypothesis that up-regulation of SMP30 inhibits cardiac adverse remodeling in response to angiotensin II.

Methods

We generated transgenic mice with cardiac-specific overexpression of SMP30 gene using α-myosin heavy chain promoter. Transgenic mice and wild-type littermate mice were subjected to continuous angiotensin II infusion (800 ng/kg/min).

Results

After 14 days, heart weight and left ventricular weight were lower in transgenic mice than in wild-type mice, although blood pressure was similarly elevated during angiotensin II infusion. Cardiac hypertrophy and diastolic dysfunction in response to angiotensin II were prevented in transgenic mice compared with wild-type mice. The degree of cardiac fibrosis by angiotensin II was lower in transgenic mice than in wild-type mice. Angiotensin II-induced generation of superoxide and subsequent cellular senescence were attenuated in transgenic mouse hearts compared with wild-type mice.

Conclusions

Cardiac-specific overexpression of SMP30 inhibited angiotensin II-induced cardiac adverse remodeling. SMP30 has a cardio-protective role with anti-oxidative and anti-aging effects and could be a novel therapeutic target to prevent cardiac hypertrophy and remodeling due to hypertension.     

Effect of simvastatin on remodeling of the left ventricle and aorta in L-NAME-induced hypertension

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to prevent or reverse hypertrophy of the LV in several models of left ventricular hypertrophy. The aim of the present study was to determine whether treatment with simvastatin can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) remodeling in NG-nitro-L-arginine methyl ester(L-NAME)-induced hypertension. Four groups of rats were investigated: control, simvastatin (10 mg/kg), L-NAME (40 mg/kg) and L-NAME + simvastatin (in corresponding doses). Animals were sacrificed and studied after 6 weeks of treatment. The decrease of NO-synthase activity in the LV, kidney and brain was associated with hypertension, LV hypertrophy and fibrosis development and remodeling of the aorta in the L-NAME group. Simvastatin attenuated the inhibition of NO-synthase activity in kidney and brain, partly prevented hypertension development and reduced the concentration of coenzyme Q in the LV. Nevertheless, myocardial hypertrophy, fibrosis and enhancement of DNA concentration in the LV, and remodeling of the aorta were not prevented by simultaneous simvastatin treatment in the L-NAME treated animals.We conclude that the HMG-CoA reductase inhibitor simvastatin improved nitric oxide production and partially prevented hypertension development, without preventing remodeling of the left ventricle and aorta in NO-deficient hypertension.     

年龄与老年高血压并发心力衰竭患者发生多器官功能衰竭的关系

目的:分析年龄对老年高血压患者伴发心力衰竭(CHF)后诱发多器官功能衰竭(MODSE)的关系,探讨年龄和CHF对老年高血压患者发生MODSE的预测值。方法:回顾性分析≥60岁高血压患者的19996例病历资料(男性13229例,女性6767例,平均年龄74.21±7.52),以10岁为界60~69岁、70~79岁、80~89岁和≥90岁划分年龄段,以69、79和89岁为分界点,分别分析各年龄段及各分界年龄上下老年高血压患者中因CHF并发MODSE的发生率。结果:①所有CHF患者中MODSE的发生率较非CHF患者升高(7.43%vs3.05%,χ2195.15,说明CHF是影响老年高血压患者出现MODSE的重要影响因素;②60~69岁、70~79,80~89岁和≥90岁发生CHF的比例分别10.60%vs18.88%vs30.11%vs60.57%,P<0.05,差异有统计学意义。4个年龄段发生MODSE分别为1.68%vs7.06%vs17.08%vs25.47%,P<0.05,有统计学差异。高血压患者中CHF的发生率与CHF中MODSE的发生率呈正相关r=0.696(P<0.01);年龄与老年高血压患者并发CHF的发生率以及年龄与CHF中MODSE发生率亦呈正相关r=0.987(P<0.01)。排除年龄因素的影响对CHF与MODSE的发生率进行偏相关分析表明r=-0.776(P>0.05),说明年龄是老年高血压患者并发CHF后出现MODSE的重要影响因素,且69岁以上各分界年龄上下之间差异最明显,具有统计学意义(P<0.05)。结论:年龄与CHF诱发老年高血压患者发生MODSE具有一定的早期预测值,69岁以上的高血压患者如合并CHF是发生MODSE的高危人群。     

吴茱萸次碱对肺动脉高压大鼠右心室重构的影响

目的：观察吴茱萸次碱（Rut）对野百合碱（MCT）诱导的肺动脉高压（PH）大鼠右心室重构的作用及机制。方法：SD大鼠48只适应性喂养一周,随机分为正常对照组、Mcr组、MCT＋Rut（20mg／kg）及Mcr＋Rut（40mg／kg）剂量组（n=12）。MCT（60mg／kg）皮下注射诱导PH大鼠模型。连续给药4周后,右颈外静脉插管测定大鼠右心室收缩压（RVSP）、平均肺动脉压（MPAP）。分离大鼠右心室（RV）、左心室＋室间隔（LV＋s）并称重,剥离大鼠胫骨并测量其长度,计算av／（LV＋s）gRV／胫骨长度的比值。HE染色观察右心室病理学变化,Masson染色观察右心室胶原沉积的变化。比色法测定右心室总抗氧化能力（T-AOC）、丙二醛（MDA）含量。Real time PCR、Western blot及免疫组化检测右心室NADPH氧化酶4（NOX4）mRNA和蛋白表达。结果：Rut连续给药4周后能明显降低MCT诱导的PH大鼠RVSP及mPAP,减轻RV／（Lv＋s）及RV重量／胫骨长度的比值,改善右心室病理变化,降低右心室胶原的沉积及collagenI、collagenHI的表达,提高右心室T-AOC水平,降低右心室NOX4的表达及MDA含量。结论：Rut能够缓解野百合碱诱导的PH大鼠右心室重构,其机制可能与抑制NOX4的表达,进而降低氧化应激损伤有关。     

Serum interleukin-6 concentration reflects the extent of asymptomatic left ventricular dysfunction and predicts progression to heart failure in patients with stable coronary artery disease

BackgroundLeft ventricular ejection fraction (LVEF) remains one of the strongest predictors of long-term prognosis in patients with stable coronary artery disease (CAD). Asymptomatic left ventricular systolic dysfunction (LVSD) often precedes clinically overt heart failure (HF) and is an area of extensive research nowadays. We studied the association between serum IL-6 concentrations and the extent of LV dysfunction in patients with asymptomatic LVSD. We aimed to investigate the diagnostic value of serum IL-6 concentrations in predicting the risk of progression to HF. Seventy-one patients entered the study and were divided into three groups based on LVEF: group 1 – patients with LVEF <30% (N = 7), group 2 – patients with LVEF 30–50% (N = 37) and group 3 – patients with LVEF >50% (N = 27).ResultsDemographics were similar in all three groups. IL-6 concentration was the highest in group 1 (median 8.6 pg/mL) and the lowest in group 3 (median 2.6 pg/mL), whereas IL-6 concentration in group 2 was intermediate (median 3.7 pg/mL) (P = 0.002). We found a significant, inverse correlation between IL-6 concentration and ejection fraction. During 18-month follow-up clinically overt HF developed in 71.4% of patients in group 1 and in 37.5% of patients in group 2. None of the patients in group 3 manifested HF symptoms (P < 0.001). ROC analysis revealed high diagnostic value of serum IL-6 and LVEF in predicting progression to HF. We also found a strong, inverse correlation between IL-6 and the time of progression to HF.ConclusionsThere is a strong correlation between IL-6 and the extent of asymptomatic LVSD in patients with documented CAD. Elevated IL-6 concentrations preceded progression to clinically overt HF. Moreover, the higher the IL-6 concentration the earlier the manifestation of HF symptoms.     

Effects of endogenous serum neuregulin-1β on morbidity and mortality in patients with heart failure and left ventricular systolic dysfunction

Abstract

Context: Improved left ventricular ejection fraction (LVEF) following administration of recombinant human Neuregulin-1β (NRG), epidermal growth factor (EGF) involved in cardiomyocyte repair/survival, has been observed in patients with systolic heart failure (HF).

Methods: Serum NRG was measured by ELISA in 248 patients with NYHA class I–IV HF.

Results: NRG exhibited a marginally significant effect on LVEF trajectory over 11?months (p?=?0.07). There is no apparent level of NRG that predicts improved survival.

Conclusions: There is a potential relationship between serum NRG and improved LVEF, indicating the need to investigate the utility of NRG in predicting HF outcomes, including LVEF maintenance.     

SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension

Abstract

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH).

Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n?=?34) and maladaptive RV (n?=?32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n?=?18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n?=?21).

Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p?<?0.01), DCM (p?<?0.001) or controls (p?<?0.001). Patients with adaptive RV function had higher SPARCL1 concentrations than controls (p?<?0.05), whereas there was no difference between adaptive RV and DCM. SPARCL1 showed good predictive power for maladaptive RV (AUC 0.77, p?<?0.001) with an optimal cut-off value of 9.66?ng/ml. The TAPSE/PASP ratio was the only independent predictor of SPARCL1?≥?9.66?ng/ml in multivariable logistic regression analysis.

Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.     

Gender differences in selected zinc metabolism parameters in patients with mild primary arterial hypertension

The relationship between selected zinc (Zn) metabolism parameters, arterial blood pressure, age, and renin-angiotensin-aldosterone system in subjects of both sexes with mild primary arterial hypertension is presented in this study. The following parameters were measured: systolic and diastolic arterial blood pressure, total and ouabain-dependent efflux rate constants of Zn from lymphocytes, serum and lymphocyte Zn concentrations, serum aldosterone, angiotensin-converting enzyme, sodium and potassium concentrations, body mass index, and plasma rennin activity. When all subjects are taken into account, no significant age-related differences were found for serum Zn. If divided into men and women, negative (r=−0.39) and positive (r=0.34) correlations are observed, respectively. Lymphocyte Zn correlated negatively with age in the entire group (r=−0.55) and also for men (r=−0.54) and women (r=−0.57). The renin-agiotensin-aldosterone system parameters correlated with those of Zn metabolism only for women: plasma rennin activity with total Zn efflux from lymphocytes (r=−0.33) and with lymphocyte Zn (r=0.71); the angiotensin-converting enzyme with total Zn efflux from lymphocytes (r=−0.35), with the oubain-dependent Zn efflux from lymphocytes (r=−0.33) and with lymphocyte Zn (r=0.57); serum aldosterone with oubain-dependent Zn efflux from lymphocytes (r=−0.44) and with lymphocyte Zn (r=0.59). For the men, the only positive correlation was that of serum Zn and aldosterone (r=0.45). In all cases (men and women), there was no negative correlation between serum Zn and angiotensin-converting enzyme. In women, the diastolic blood pressure correlated negatively with total Zn efflux from lymphocytes (r=−0.39), oubain-dependent Zn efflux from lymphocytes (r=−0.49), and serum Zn (r=−0.46); systolic blood pressure correlated negatively with lymphocyte zinc (r=−0.38). In men, the systolic blood pressure had a negative correlation with lymphocyte zinc (r=−0.32), which was also true for the entire group (r=−0.34). These results clearly show gender-related differences in Zn metabolism and indicate the need for further research to elucidate the possible causes of this phenomenon not only for Zn but for other elements as well.     

Correlations between serum zinc concentrations and oxygen balance parameters in patients with primary arterial hypertension

It has been postulated that increased blood pressure is related to hypersensitivity of arterial chemoreceptors and increased tissue oxygen supply. Arterial blood pressure has been found to be negatively correlated to serum zinc and positively correlated to age, body mass index, and hemoglobin concentrations. The aim of the present investigation was to further explore the relationship between blood pressure and zinc concentrations in serum and blood morphology parameters, iron concentrations, and venous blood gasometry parameters. The study was carried out in two groups. Group Aconsisted of 23 subjects of both sexes suffering from moderate to severe arterial blood pressure. Their mean age was 53.13±10.45 yr (range: 23–74 yr). Group B included 48 subjects of mean age 36.7±10.0 yr (range: 26–60 yr). This group included 5 patients with arterial hypotension, 37 with hypertension, and the remaining 6 with normal blood pressure. Significant positive correlations between serum zinc and red blood cell count (r = 0.51) and negative with age (r = −0.52) were found. By multiple regression, negative correlations were also found between serum zinc and the diastolic blood pressure and with hemoglobin (r = −0.5). Age was positively correlated to systolic (r = 0.49) and diastolic (r = 0.45) blood pressure parameters and to hemoglobin concentrations (r = 0.33 and r = 0.38, respectively). Buffered and excess bases in blood were negatively correlated to zinc (r = −0.29 in both cases) and to systolic and diastolic blood pressure (r = −0.31 and r = −0.40, respectively). In turn, the systolic and diastolic blood pressure also correlated negatively to the partial pressure of carbon dioxide and positively to venous blood oxygen saturation and to the partial pressure of oxygen. The role of zinc and acid-balance realtionships in blood pressure regulation and in arterial hypertension ethiopatogenesis is disscused.     

A novel adipocytokine,omentin, inhibits monocrotaline-induced pulmonary arterial hypertension in rats

Omentin is a novel adipocytokine mainly expressed in visceral rather than subcutaneous adipose tissue. Several epidemiological studies demonstrated the negative relationship between blood omentin level and occurrence of obesity, type 2 diabetes and hypertension. Increases of inflammatory responses, contractile reactivity and structural remodeling of vascular wall contribute to hypertension development. Our in vitro studies previously demonstrated that omentin inhibited those hypertension-related pathological processes. In addition, our in vivo study demonstrated that intravenously injected omentin acutely inhibited agonists-induced increases of blood pressure in rats. However, the chronic effects of omentin on hypertension development are not determined. In the present study, we tested the hypothesis that chronic omentin treatment may inhibit pulmonary arterial (PA) hypertension (PAH). PAH was induced by a single intraperitoneal injection of monocrotaline (MCT: 60 mg/kg) to rats. Omentin (18 μg/kg/day) was intraperitoneally treated for 14 days. Chronic omentin treatment inhibited MCT-induced increases in PA pressure. Omentin inhibited MCT-induced right ventricular hypertrophy as well as increase of lung to body weight ratio. Histologically, omentin inhibited MCT-induced PA hyperplasia. Further, omentin inhibited the impairment of both endothelium-dependent and -independent relaxations mediated by acetylcholine and sodium nitroprusside, respectively. In conclusion, we for the first time demonstrate that chronic omentin treatment inhibits MCT-induced PAH in rats via inhibiting vascular structural remodeling and abnormal contractile reactivity.     

The effect of bone marrow-derived cells on diastolic function and exercise capacity in patients after acute myocardial infarction

The purpose of this study is to establish a murine embryonic stem cell (mESC) line for isolation of functional ventricular cardiomyocytes (VCMs) and then to characterize the derived VCMs. By crossing the myosin light chain 2v (Mlc2v)-Cre mouse line with the reporter strain Rosa26-yellow fluorescent protein (YFP), we generated mESC lines from these double transgenic mice, in which Cre-mediated removal of a stop sequence results in the expression of YFP under the control of the ubiquitously active Rosa26 promoter specifically in the VCM. After induction of differentiation via embryoid body (EB) formation, contracting YFP⁺ cells were detected within EBs and isolated by fluorescence-activated cell sorting. N-cadherin, the cadherin expressed in cardiomyocytes, and the major cardiac connexin (Cx) isoform, Cx43, were detected in the respective adherens and gap junctions in these VCMs. Using current clamp recordings we demonstrated that mESC-derived VCMs exhibited action potential characteristics comparable to those of neonatal mouse VCMs. Real-time intracellular calcium [Ca²⁺]_i imaging showed rhythmic intracellular calcium transients in these VCMs. The amplitude and frequency of calcium transients were increased by isoproterenol stimulation, suggesting the existence of functional β-adrenergic signaling. Moreover, [Ca²⁺]_i oscillations responded to increasing frequencies of external electrical stimulation, indicating that VCMs have functional excitation-contraction coupling, a key factor for the ultimate cardiac contractile performance. The present study makes possible the production of homogeneous and functional VCMs for basic research as well as for cardiac repair and regeneration.