Development Of Left Ventricular Hypertrophy Research Articles

Lack of salt-inducible kinase 2 (SIK2) prevents the development of cardiac hypertrophy in response to chronic high-salt intake.

Cardiac left ventricle hypertrophy (LVH) constitutes a major risk factor for heart failure. Although LVH is most commonly caused by chronic elevation in arterial blood pressure, reduction of blood pressure to normal levels does not always result in regression of LVH, suggesting that additional factors contribute to the development of this pathology. We tested whether genetic preconditions associated with the imbalance in sodium homeostasis could trigger the development of LVH without concomitant increases in blood pressure. The results showed that the presence of a hypertensive variant of α-adducin gene in Milan rats (before they become hypertensive) resulted in elevated expression of genes associated with LVH, and of salt-inducible kinase 2 (SIK2) in the left ventricle (LV). Moreover, the mRNA expression levels of SIK2, α-adducin, and several markers of cardiac hypertrophy were positively correlated in tissue biopsies obtained from human hearts. In addition, we found in cardiac myocytes that α-adducin regulates the expression of SIK2, which in turn mediates the effects of adducin on hypertrophy markers gene activation. Furthermore, evidence that SIK2 is critical for the development of LVH in response to chronic high salt diet (HS) was obtained in mice with ablation of the sik2 gene. Increases in the expression of genes associated with LVH, as well as increases in LV wall thickness upon HS, occurred only in sik2+/+ but not in sik2−/− mice. Thus LVH triggered by HS or the presence of a genetic variant of α-adducin requires SIK2 and is independent of elevated blood pressure. Inhibitors of SIK2 may constitute part of a novel therapeutic regimen aimed at prevention/regression of LVH.

Impact of the PPARGC1A Gly482Ser polymorphism on left ventricular structural and functional abnormalities in patients with hypertension

The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A) has been reported to contribute to the development of left ventricular (LV) hypertrophy. Little is known, however, about its possible impact on cardiac dysfunction. Enhanced myocardial fibrosis accompanying increased LV mass might represent a link with coexisting functional abnormalities. We investigated the association between the PPARGC1A Gly482Ser polymorphism and LV morphology and performance in essential hypertension, with special consideration of fibrosis intensity. A total of 205 hypertensive patients (60±8 years) underwent echocardiography with assessment of cardiac morphology, LV systolic (strain and strain rate) and diastolic function (peak early diastolic mitral flow velocity/peak late diastolic mitral flow velocity (E/A) ratio, peak early diastolic myocardial velocity (Em), and E/e' ratio (where e' is the peak early diastolic mitral annular velocity)), evaluation of serum procollagen type III amino-terminal propeptide (PIIINP) and procollagen type I carboxy-terminal propeptide (PICP)-markers of fibrosis and the PPARGC1A Gly482Ser genotyping. Subjects with the Ser-Ser genotype demonstrated more profound LV hypertrophy and diastolic function impairment, and higher PICP/PIIINP than the Ser-Gly and Gly-Gly groups. In multivariable analysis, the presence of the Ser-Ser allele was an independent correlate of E/e' (β=0.17, P<0.02), Em (β=-0.18, P<0.01) and LV mass index (β=0.28, P<0.001). In conclusion, in hypertensive patients, the PPARGC1A Gly482Ser polymorphism is associated with LV hypertrophy and diastolic dysfunction, with the presence of the Ser-Ser allele promoting these abnormalities. One of the possible mechanisms mediating the adverse effect on diastolic performance might be a relative increase in the anabolism of rigid collagen type I over that of the more elastic collagen type III, as indicated by an increased ratio of PICP to PIIINP.

Transient receptor potential vanilloid 2 is a mediator of left ventricular hypertrophy (862.5)

Background: Impaired calcium handling has been implicated in the development of left ventricular hypertrophy (LVH) and subsequent development of heart failure (HF). We have recently shown that the calcium channel Transient Receptor Potential Vanilloid 2 (TRPV2) is present in cardiomyocytes and regulates contractility on a beat to beat basis. This study was performed to elucidate if TRPV2 also modulates the development of LVH in a pressure overload mouse model via transverse aortic constriction (TAC).Methods: WT and TRPV2‐/‐ mice were subjected to pressure overload via TAC and followed echocardiographically for 8 weeks. A subgroup of WT mice were treated with a nonspecific TRPV2 antagonist (tranilast) for the same amount of time. At the conclusion, the hearts were collected for molecular and histological analysis of hypertrophy.Results: There was significantly less hypertrophy in TRPV2‐/‐ and in the WT mice treated with tranilast (n=5 and 2) in comparison to untreated WT mice (n=7) as noted via heart weight: body weight ratio and LV mass via echocardiography (P&lt;0.05; TRPV2 vs. untreated WT). Furthermore, there was a trend towards improved contractility and less LV cavity dilation in the TRPV2‐/‐ and the WT treated mice in comparison to untreated mice.Conclusions: We have shown that TRPV2 modulates the development of LVH and is a potential target for the prevention and treatment of LVH and development of HF.

Ethanol exposure alters zebrafish morphology and development, evidence of impaired adipogenesis and adiponectin production (540.7)

Adipose tissue secretes numerous bioactive peptides (“adipocytokines”). Visceral fat mediates inflammatory cytokines. In contrast, subcutaneous fat is the principal source of adiponectin production. Adiponectin, consisting of 247 amino acids and single nucleotide polymorphisms (mutations), causes hypoadiponectinemia. Individuals with this mutation are highly susceptible for development of insulin resistance, cardiovascular disease, hypertention, and left ventricular hypertrophy. We hypothesize that alcohol consumption during pregnancy may alter endocrine signaling, by increasing pro‐inflammatory cytokines thus inducing fetal Alcohol Syndrome (FAS). Even low‐dose/or short duration ethanol exposure early in development can produce more subtle effects by alteration of subcutaneous fat and subsequently, decrease in adiponectin production. Zebrafish eggs (AB strain) were raised in water (control) or in 0.5%, 1%, 1.5%, 2%, and 2.5% ethanol solution for one of 3dpf, 5 dpf, 10 dpf, 15dpf, or 20dpf. Anatomical measures including heart diameter and total body length were compared across groups. At the concentration of 2.5%, there were more abnormal physical distortions and significantly higher mortality rates than any other group.Nile Red (NR) and Oil Red O (ORO) staining was used to detect adipogenesis (visceral vs subcutaneous) fat depots. Adipogenesis during zebrafish development was altered and subcutaneous fat was depleted at 15pft after 2% alcohol exposure compared with control. The expression of an “adipogenic” transcriptional program including PPARγ, SREBP1c, CEBPα □ and pro‐inflammatory cytokines IL‐6, IL‐8, HIF‐1α ROS, TNF‐α, and NF‐κB was altered, as evident from quantitative RT‐PCR analysis. We conclude that exposure of zebrafish larvae to ethanol during development results in modified external and internal morphological development and that the severity of these effects is due to remarkable changes in adiposity and hypoadiponectinemia.Grant Funding Source: NSF

Whole-genome profiling highlights the molecular complexity underlying eccentric cardiac hypertrophy

Heart failure is typically preceded by myocardial hypertrophy and remodeling, which can be concentric due to pressure overload (PO), or eccentric because of volume overload (VO). The molecular mechanisms that underlie these differing patterns of hypertrophy are distinct and have yet to be fully elucidated. Thus, the goal of this work is to identify novel therapeutic targets for cardiovascular conditions marked by hypertrophy that have previously been resistant to medical treatment, such as a pure VO. Concentric or eccentric hypertrophy was induced in rats for 2 weeks with transverse aortic constriction (TAC) or aortocaval fistula (ACF), respectively. Hemodynamic and echocardiographic analysis were used to assess the development of left ventricular (LV) hypertrophy and functional differences between groups. Changes in gene expression were determined by microarray and further characterized with Ingenuity Pathway Analysis. Both models of hypertrophy increased LV mass. Rats with TAC demonstrated concentric LV remodeling while rats with ACF exhibited eccentric LV remodeling. Microarray analysis associated eccentric remodeling with a more extensive alteration of gene expression compared with concentric remodeling. Rats with VO had a marked activation of extracellular matrix genes, promotion of cell cycle genes, downregulation of genes associated with oxidative metabolism, and dysregulation of genes critical to cardiac contractile function. Rats with PO demonstrated similar categorical changes, but with the involvement of fewer individual genes. Our results indicate that eccentric remodeling is a far more complex process than concentric remodeling. This study highlights the importance of several key biological functions early in the course of VO, including regulation of matrix, metabolism, cell proliferation, and contractile function. Thus, the results of this analysis will inform the ongoing search for new treatments to prevent the progression to heart failure in VO.

Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation

Objectives. We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. Design. Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. Results. Eight pigs died and seven were excluded due to mediastinal infection (n = 2) or failure to produce MR (n = 5). Thus, 28 pigs were included and were divided into three groups: controls (n = 12), mild MR (mMR; n = 10), and moderate to severe MR (sMR; n = 6). The change in LV internal diameter in diastole (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to that of the control group (P = 0.0017). Furthermore, LV weight was significantly increased in the mMR (P = 0.047) and the sMR (P = 0.0087) groups compared to that of the control group. Conclusions. A new model for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs.

Vitamin D Receptor Gene Polymorphism and Left Ventricular Hypertrophy in Chronic Kidney Disease

FokI and BsmI polymorphisms of vitamin D receptor (VDR) gene are regarded as reliable markers of disturbed vitamin D signaling pathway. Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end stage renal disease (ESRD) patients. Since BsmI polymorphism has been associated with LVH in ESRD patients, we addressed this study in patients with chronic kidney disease (CKD) not yet on dialysis. One hundred and forty five patients with CKD stage 3 were genotyped for FokI and BsmI VDR polymorphisms, in order to assess the relationships between these VDR polymorphisms, some markers of mineral bone disorders, and LVH measured by echocardiography. Patients bearing either the Ff heterozygous or FF homozygous genotype had significantly higher PTH values than those bearing the ff genotype. The relationships between VDR genotypes and LVH revealed a highly significant association of the BsmI Bb heterozygous genotype with LVH. In patients with CKD stage 3 BsmI B allele was independently related to LVH. Since LVH is a frequent finding in dialysis population due to several mechanisms, the presence of the same relationship in patients with CKD strengthens the hypothesis that alterations of vitamin D signaling are implicated in LVH development in patients with renal diseases.

Three-dimensional speckle tracking echocardiography for left atrial and left ventricular function in hypertrophic cardiomyopathy mutation carriers

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disorder and is the leading cause of sudden cardiac death in young individuals and athletes. It is caused by mutations in genes that encode for sarcomere proteins and is characterized by unexplained left ventricular (LV) hypertrophy (LVH). However, the penetrance of LVH is incomplete, highly variable, and age dependent. Recent reports have suggested that HCM mutation carriers without overt LVH frequently have risk factors for sudden cardiac death. Genetic testing provides a certain diagnosis for HCM mutation carriers before development of LVH, though it is hampered by being complex and unfeasible in up to 50% of HCM family members as genetic mutations are only identified in 40–60% of HCM patients. Therefore, an alternative family screening approach for early diagnosis of HCM patients is required. LV diastolic dysfunction as the first marker of disease in preclinical HCM mutation carriers has been previously detected by tissue Doppler imaging (TDI). However, the reported sensitivity and specificity were highly variable. Other imaging tools for the early identification of myocardial systolic dysfunction and myocardial structural alteration such as two–dimensional speckle tracking echocardiography (2DSTE) and integrated backscatter echocardiography, respectively were also investigated albeit with mixed results. Recently, cardiac magnetic resonance (CMR) imaging with its high spatial resolution has displayed subtle myocardial structural changes but also intramyocardial crypts in these mainly asymptomatic patients. However the availability of CMR is limited and the analysis is time consuming. Quantification of LA size and function is a good diagnostic tool for LV diastolic function as well as a predictor of therapy response and major cardiovascular outcomes in various cardiac patients including HCM patients. The assessment of left atrial (LA) longitudinal strain using 2DSTE has recently been shown as a feasible and reproducible marker of LA function. Three–dimensional speckle tracking echocardiography (3DSTE) is an emerging tool building on the strengths of 2DSTE for better quantification of myocardial volumes and mechanics including assessment of dyssynchrony in one fast analysis. In this study, we tested the ability of 3DSTE to distinguish HCM mutation carriers from normal subjects primarily by detecting subtle abnormalities in LA size and longitudinal strain as surrogate markers of early LV dysfunction. Likewise, we evaluated the magnitude and timing of systolic myocardial deformation to detect any abnormalities that can define early systolic dysfunction in these subjects. A total of 80 subjects with normal LV ejection fraction (EF) were divided into 3 groups: HCM mutation carriers ( n = 23), manifest HCM patients ( n = 28), and normal controls ( n = 29). They prospectively underwent 3DSTE for left atrial (LA) and LV strain analysis. HCM mutation carriers showed significantly higher LA minimum volume (ml/m 2 ) (17 ± 6 vs. 14 ± 4, respectively, P = 0.03) and a significantly lower peak atrial longitudinal strain (PALS) (%), (27 ± 5 vs. 31 ± 7, respectively, P = 0.02) when compared to controls. However, no differences were found in global or regional LV systolic myocardial deformation between carriers and normal controls. Manifest HCM patients, compared to carriers showed significantly higher LA minimum (27 ± 10 vs. 17 ± 6, respectively, P < 0.001) and maximum volume (42 ± 14 vs. 32 ± 8, respectively, P = 0.007) as well as lower LA EF (%) (35 ± 8 vs. 47 ± 9, respectively, P < 0.001) and PALS (17 ± 5 vs. 27 ± 5, respectively, P < 0.001). Comparing LV strain, HCM patients showed reduced global longitudinal (−11 ± 4 vs. −16 ± 3, respectively, P < 0.001) and area strain (−35 ± 6 vs. −40 ± 5, respectively, P = 0.005). In addition, there was higher mechanical dyssynchrony (SDI) in the long-axis motion (13.6 ± 10 vs. 8.3 ± 4, respectively, P = 0.007). HCM mutation carriers could be distinguished from healthy subjects using 3DSTE through detection of LA dysfunction that might indicate subtle LV dysfunction. No differences were found in LV systolic myocardial deformation between both groups. The exact clinical value of 3DSTE in family screening for HCM needs to be further evaluated.

The impact of glucose load on left ventricular mass in peritoneal dialysis patients

Cardiovascular (CV) complications are the main cause of morbidity and mortality in peritoneal dialysis (PD) patients. Left ventricular hypertrophy (LVH) is a well-known major CV risk factor. To evaluate the impact of peritoneal glucose load on left ventricular mass (LVM) in PD patients. In this cross sectional study the glucose load and LVM were evaluated in 43 stable patients on maintenance PD for 24 - 78 months. Glucose load was calculated using a unique peritoneal glucose load index (PGLI) referred to g/kg/day glucose given in the daily PD prescription. LVM index (LVMI) was calculated using the Devereux et al. formula. The PGLI was positively correlated with HbA1c and LVMI (p < 0.001). Patients with PGLI > 3 g/kg/day had higher HbA1c and LVMI compared to those with PGLI ≤ 3 g/kg/day (p < 0.001). Higher PGLI values were associated with worse glycemic control and increased LVMI. Efforts should be made to minimize the PGL. All other risk factors that may contribute to the development of LVH in PD patients should be identified and treated. Additional multicenter, randomized control trials are needed to determine the target objectives of PGLI.

Adiponectin as an Independent Predictor of Left Ventricular Hypertrophy in Nondiabetic Patients With Hypertension

We evaluated novel and traditional biomarkers as well as hemodynamic parameters associated with the development of left ventricular hypertrophy (LVH) in nondiabetic patients with hypertension. Nondiabetic patients with hypertension (n = 86) were evaluated for lipids, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), adiponectin, aldosterone, renin, matrix metalloproteinase 2, and endothelin. Arterial elasticity was evaluated using pulse wave contour. The LVH parameters were assessed echographically. Adiponectin was significantly and inversely associated with left ventricular mass (LVM; P = .032). The aldosterone-renin ratio (ARR) was significantly, positively associated with LVM (P = .031). Fasting insulin as well as HOMA-IR was significantly, positively associated with LVM (P = .036 and P = .025, respectively). In multiple linear regression analysis, adiponectin and ARR remained a significant predictor of LVM. The present study found that adiponectin and ARR are important independent determinants of LVH in nondiabetic patients with hypertension.

Differential Influence of Vitamin D Analogs on Left Ventricular Mass Index in Maintenance Hemodialysis Patients

Secondary hyperparathyroidism (SHPT) is a common feature in maintenance hemodialysis (MHD) patients. Inadequate treatment of SHPT has been associated with cardiovascular complications, and vitamin D therapy might influence the development of cardiovascular diseases. In the present study, we aimed to evaluate the effects of intravenous paricalcitol and calcitriol treatments on left ventricular mass index changes in MHD patients. We conducted an observational study with a 12-month follow-up duration to compare the outcomes of intravenous paricalcitol and calcitriol treatments in MHD patients. Eighty patients with moderate to severe SHPT were enrolled in the study. All the patients had normalized total serum Ca concentration <10.5 mg/dL, serum calcium-phosphorus product (Ca × P) <75, and parathyroid hormone level (PTH) level ≥300 pg/mL at the begining of the follow-up period. The patients were divided into a paricalcitol group (n = 40) and a calcitriol group (n = 40). The demographic, clinical, and biochemical characteristics of the patients were similar at baseline. We observed significantly superior control of SHPT; lesser frequency of hypercalcemia and hyperphosphatemia, and Ca × P level elevations; and interruption of vitamin D treatment in the paricalcitol group. Moreover, we found no significant change in left ventricular mass index in the paricalcitol group, but found a significantly increased left ventricular mass index in the calcitriol group during the follow-up period (from 136.6 ± 35.2 g/m2 to 132.9 ± 40.4 g/m2 vs. from 137.2 ± 30.1 g/m2 to 149.4 ± 31.0 g/m2; p<0.044). We observed that, compared with calcitriol therapy, paricalcitol therapy reduced the PTH concentrations more effectively without causing hypercalcemia and hyperphosphatemia and might have a substantial beneficial effect on the development of left ventricular hypertrophy.

Pathophysiology of anemia in chronic kidney diseases: A review

Backgroud. Anemia is one of the laboratory and clinical findings of chronic kidney diseases (CKD). The presence of anemia in patients with CKD has a wide range of clinically important consequences. Some of the symptoms that were previously attributed to reduced renal function are, in fact, a consequence of anemia. Anemia contributes to increased cardiac output, the development of left ventricular hypertrophy, angina, and congestive heart failure. According to current knowledge, anemia also contributes to the progression of CKD and is one of the factors that contribute to the high morbidity and mortality in patients with chronic renal failure and their reduced survival. MEDLINE search was performed to collect both original and review articles addressing anemia in CKD, pathophysiology of renal anemia, erythropoiesis, erythropoietin, iron metabolism, inflammation, malnutrition, drugs, renal replacement therapy and anemia management The present review summarized current knowledge in the field of the pathophysiology of renel anemia. Understanding the pathophysiology of anemia in CKD is crucial for the optimal treatment of anemia according to recent clinical practice guidelines and recommendation, and correct recognition of causes of resistence to treatment of erythropoietin stimulating agents (ESA).

Determinants of left ventricular hypertrophy in patients with recent diagnosis of essential hypertension

Development of left ventricular hypertrophy (LVH) is a multifactorial phenomenon. We retrospectively assessed the risk factors for LVH in patients with recent diagnosis of essential hypertension. We analysed 1518 participants with recent diagnosis of essential hypertension (≤2 years). The duration of hypertension was established after cross-checking the patients' history and the records of the general practitioners'. The following cardiovascular (CV) risk factors were considered: age (men >55 years, women >65 years), SBP >140 mmHg, DBP >90 mmHg, obesity, diabetes, hypercholesterolemia, low or high-density lipoprotein (HDL)-cholesterol (men <40 m/dl, women <50 mg/dl), and chronic kidney disease (CKD). Age, prevalence of metabolic diseases, CKD, and the severity of hypertension were higher in patients with LVH. One hundred twenty-two (8%) patients did not have CV risk factors, whereas 288 (19%), 472 (31.1%), 351 (23.1%) and 285 (18.8%) patients had one, two, three and more than three CV risk factors, respectively. At univariate analysis, CV risk factors for LVH where found to be sex, age, SBP, low HDL-cholesterol, obesity, diabetes, CKD, and metabolic syndrome. In the multivariate analysis, the independent predictors of LVH were found to be sex, age, SBP, obesity and diabetes. A significant correlation was found between indexed left ventricular mass and body mass index (r(2) = 0.167), age (r(2) = 0.077) and SBP (r (2)= 0.055). This study reveals that, in patients with recent diagnosis of essential hypertension obesity represents the most important modifiable CV risk factor for LVH.

Features of structural and functional changes of the myocardium in patients with chronic viral hepatitis

Our aim was to evaluate the characteristics of structural and functional changes of the heart in patients with chronic viral hepatitis. The study included 123 patients - 17 patients with aviraemnia after antiviral therapy (group 1), 38 patients with laboratory inactive hepatitis (group 2), 68 patients with biochemical active hepatitis (group 3). All patients had standard echocardiography, Doppler sonography and tissue Doppler echocardiography. Patients with chronic viral hepatitis were revealed to develop changes in the geometry of the left ventricle (increase in the wall thickness). Patients with active hepatitis had increase in the left atrium, the right ventricle and indexed left ventricular mass of the heart. Significant morphological changes were not confirmed statistically in patients after "therapy". Pulmonary hypertension was revealed in 19% of cases, mitral valve prolapse was confirmed in 48%, with the detection rates being not dependent on hepatitis activity. Abnormal left ventricular remodeling was identified in 45% of patients, in patients with active hepatitis more frequently. Compliance dysfunction of both right and left ventricles was detected, it depends on the activity of the inflammatory process in the liver. This disorder partially persists after antiviral treatment. Specifics of the structural and functional changes of the heart in patients with chronic viral hepatitis is the development of left ventricular hypertrophy, and in the presence of laboratory activity hepatitis - relative dilatation of the right heart and ventricular diastolic dysfunction of the heart. Carrying out specific antiviral therapy has a beneficial effect on cardiac hemodynamics parameters. Method of tissue Doppler echocardiography was efficient in evaluation of early disorders of diastolic function in patients with chronic viral hepatitis.

The Gene Polymorphism of LOX1 Predicts the Incidence of LVH in Patients with Essential Hypertension

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been shown to play an important role in cardiac remodeling under different pathologic conditions. The role of genetic polymorphisms in the LOX1 gene, however, remains unclear in the development of left ventricular hypertrophy (LVH) for patients with hypertension. Methods: A total of 536 patients diagnosed with essential hypertension (EH) were recruited in this study. Patients were assigned to the LVH+ (n=143) and LVH- (n=393) groups, respectively. The serum LOX1 level was measured and three single nucleotide polymorphisms (SNPs), i.e. intron 4 (G→A), intron 5(T→G), and 3′ UTR (T→C) of the LOX1 gene were genotyped. Results: The genotype frequencies of intron 4 G>A and 3′UTR T>C were not significantly different between the LVH+ and LVH- groups (both P>0.05), however, frequencies of 501G>C were significantly different between those two groups (P=0.007). The 501CC genotype carriers had a markedly higher serum LOX1 level and an increased risk to develop LVH (adjusted OR=2.444, adjusted P=0.002). There was a positive correlation between serum LOX1 level and left ventricular mass index (r=0.907, P<0.001); a cutoff value of 1.0 ng/mL for sLOX-1 was applied to significantly differentiate the LVH+ patients from the LVH- patients with 84% sensitivity and 86% specificity. Conclusion: Our data suggest that both the 501>C SNP in the LOX1 gene and the serum LOX1 level may be used to predict the development of LVH among EH patients.

Correlation Between Endothelial Dysfunction and Left Ventricular Remodeling in Patients with Chronic Kidney Disease

Background/Aims: To investigate the role of endothelial dysfunction on left ventricular remodeling in patients with chronic kidney disease and to evaluate the correlation between endothelial dysfunction and left ventricular remodeling. Methods: Seventy-three patients with chronic kidney disease as study-group and thirty healthy volunteers as control-group were enrolled in the present study. All patients in both groups had echocardiography examination. The concentration of endothelin-1, nitric oxide, and inducible nitric oxide synthase of serum of all patients and healthy volunteers was measured. The incidence of cardiac structural abnormalities in patients with chronic kidney disease, and the relationship between endothelial dysfunction and cardiac structural abnormalities were analyzed. Results: The incidence of left ventricular hypertrophy, left ventricular concentric remodeling, and left ventricular systolic dysfunction was 65%, 8.33%, and 16.67%, respectively. The level of endothelin-1 and nitric oxide increased in study-group, and the concentration of inducible nitric oxide synthase decreased. There was significant positively relationship between plasma endothelin-1 and left ventricular mass index, interventricular septal thickness, left ventricular diastolic diameter. There was negatively relationship between the level of serum nitric oxide and the maximum flow velocity at the mitral in left ventricular diastolic stage. There was not any correlation between inducible nitric oxide synthase with left ventricular remodeling. Conclusions: The results showed that there was a higher incidence of left ventricular hypertrophy in patients with chronic kidney disease. Endothelin-1 and nitric oxide played an important role on the development of left ventricular hypertrophy. i 2014 S. Karger AG, Basel

Hypertension and cardiovascular remodelling in rats exposed to continuous light: protection by ACE-inhibition and melatonin.

Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day) or melatonin (10 mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

THE ROLE OF THE MATRIX METALLOPROTEINASES IN THE DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ARTERIAL HYPERTENSION AND METABOLIC SYNDROME

Aim. To assess the role of the activation of matrix metalloproteinase-1 zymogen (ProMMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the development of left ventricular (LV) hypertrophy in patients with arterial hypertension (HT) and metabolic syndrome (MS) with varying degree of obesity. Material and methods. 108 patients with HT and MS divided into 3 groups according to body mass index, and 28 healthy women were studied. Intracardiac blood flow and ProMMP-1 and TIMP-1 levels were assessed. Results. Disbalance in the ProMMP-1 and TIMP-1 systems is associated with the severity of left ventricular remodeling and grade of obesity. The changes in LV structure and geometry and activation ProMMP-1 with a deficit of TIMP-1 were most significant in patients with HT and grade 3 obesity (respectively 7.7±0.61 and 183.6±17.2 ng/ml in grade 3 obesity vs 3.5±0.3 and 291.7±22.4 ng/ml in grade 1 obesity; p&lt;0.05). Associations between hemodynamic parameters and levels of ProMMP-1 [withLVmass index (LVMI): r=0.47; p&lt;0.05] and TIMP-1 (with LVMI: r=-0.39; p&lt;0.05) were determined. Conclusion. Changes in the ProMMP-1 and TIMP-1 system in women with HT and MS are associated with the severity ofLVhypertrophy.

Myocardial mechanics in a rat model with banding and debanding of the ascending aorta.

BackgroundAortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH.MethodsMinimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding.ResultsBanding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 ± 0.8 vs. 33.2 ± 2.0 vs. 26.6 ± 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 ± 0.20% vs. 5.26 ± 3.12% vs. 4.03 ± 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028).ConclusionIn this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.

Serum osteopontin, but not OPN gene polymorphism, is associated with LVH in essential hypertensive patients

This study aims to investigate the role of osteopontin (OPN) genetic polymorphisms in the occurrence of left ventricular hypertrophy (LVH) in Chinese patients with essential hypertension (EH). A total of 1,092 patients diagnosed with EH were recruited. Three single nucleotide polymorphisms (SNP) on the promoter region of the OPN gene, including -66T/G, -156G/GG, and -443C/T were genotyped. The serum thrombin-cleaved OPN levels were studied. Patients were divided into LVH+ (n = 443) and the LVH- (n = 649) groups. We found that none of the studied SNPs in the OPN gene was associated with the risk and severity of LVH. The SNPs in the OPN gene did not correlate with the serum OPN levels. However, the serum thrombin-cleaved OPN levels were found to be an independent risk factor for LVH in the EH patients. Multivariate logistic regression analysis showed that serum thrombin-cleaved OPN levels were independently associated with the development of LVH (adjusted OR = 2.47, 95% CI 1.56-4.01, adjusted P < 0.001). In vitro studies showed that the thrombin-cleaved OPN treatment increased the protein content per cell, the cardiomyocyte surface size, and the expression level of atrial natriuretic peptide protein in a dose-dependent manner. The thrombin-cleaved OPN serum level, but not OPN gene polymorphism, is associated with the development of LVH in EH patients. Serum OPN is related to LVH incidence in essential hypertension subjects. OPN stimulates cardiomyocyte hypertrophy in vitro. OPN SNPs are not related to LVH incidence.