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PubMed2006

Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN.

Diabetic nephropathy is characterized early in its course by glomerular hypertrophy and, importantly, mesangial hypertrophy, which correlate with eventual glomerulosclerosis. The mechanism of hypertrophy, however, is not known. Gene disruption of the tumor suppressor PTEN, a negative regulator of the phosphatidylinositol 3-kinase/Akt pathway, in fruit flies and mice demonstrated its role in size control in a cell-specific manner. Here, we investigated the mechanism of mesangial hypertrophy in response to high extracellular glucose. We link early renal hypertrophy with significant reduction in PTEN expression in the streptozotocin-induced diabetic kidney cortex and glomeruli, concomitant with activation of Akt. Similarly, exposure of mesangial cells to high concentrations of glucose also decreased PTEN expression and its phosphatase activity, resulting in increased Akt activity. Expression of PTEN inhibited high-glucose-induced mesangial cell hypertrophy, and expression of dominant-negative PTEN was sufficient to induce hypertrophy. In diabetic nephropathy, the hypertrophic effect of hyperglycemia is thought to be mediated by transforming growth factor-beta (TGF-beta). TGF-beta significantly reduced PTEN expression in mesangial cells, with a reduction in its phosphatase activity and an increase in Akt activation. PTEN and dominant-negative Akt attenuated TGF-beta-induced hypertrophy of mesangial cells. Finally, we show that inhibition of TGF-beta signal transduction blocks the effect of high glucose on PTEN downregulation. These data identify a novel mechanism placing PTEN as a key regulator of diabetic mesangial hypertrophy involving TGF-beta signaling.

Animals↗
PubMed1990

[Influence of tonsillar hypertrophy to school-life of children].

The authors examined degree of facial tonsillar hypertrophy for 7190 pupils of elementary schools in nine different areas in Japan. The frequency of the third degree of tonsillar hypertrophy, based on Mackenzie's criteria, decreased gradually from 6.9% of the first-year pupils to 2.9% of the sixth-year pupils with a mean of 4.8%. We also studied the relation between the degree of tonsillar hypertrophy of each pupil and the reply to the questionnaire from his or her teacher regarding various aspects of his or her school-life. The third degree of tonsillar hypertrophy of each pupil and the reply to the questionnaire from his or her teacher regarding various aspects of his or her school-life. The third degree of tonsillar hypertrophy seemed to affect school-life of pupils. For example, the frequency of pupils whose speech can be clearly recognized, was less in pupils with the third degree of tonsillar hypertrophy than in pupils without any tonsillar hypertrophy. Pupils of higher grades with the third degree of tonsillar hypertrophy were classified into two groups. One was the pupils whose school-life was not altered by tonsillar hypertrophy. The other was the pupils who were often absent from school due to chronic or acute tonsillar inflammation.

Child↗
PubMed1999

[Hypertrophy of the left ventricle--etiopathogenesis, clinical consequences and prognosis].

The left ventricular hypertrophy is a risk marker of the cardiovascular morbidity and mortality in hypertensive patients--it contributes to sudden death, myocardial infarction, myocardial ischemia, heart failure, arrhythmias, left ventricular diastolic dysfunction, stroke and renal failure. The mechanisms by which the heart hypertrophy increases the risk of cardiovascular morbidity and mortality, however, is not completely clear yet. Pressure overload (resulting in the concentric hypertrophy) and volume overload (resulting in the eccentric hypertrophy) of the left ventricle play a significant role in the development of the hypertrophy of the left ventricle. Other risk factors, stimulating left ventricular hypertrophy, include growth factors, genetic predisposition, age, obesity, hyperinsulinemia and anemia. The hypertrophy of left ventricle most often occurs with hypertension, cardiomyopathy and aortic stenosis. Several clinical studies evaluated functional consequences of the reduction of the ventricular hypertrophy and found out that the function of the left ventricle to be improved in hypertensive patients who had undergone an effective and long-term antihypertensive treatment. However, these studies did not differentiate whether for the improvement in the function of left ventricle was the matter of the reduction of the left ventricular mass or whether it was because of the decrease of the arterial pressure during the period of anti-hypertensive treatment. On the basis of the literature studied we can emphasize that the reduction of myocardial hypertrophy resulting from a specific antihypertensive treatment appears to be more favourable than harmful for the heart's pump performance.

Humans↗
PubMed2001

Accelerated glycolysis and greater postischemic dysfunction in hypertrophied rat hearts are independent of coronary flow.

BACKGROUND: After ischemia, glycolysis and dysfunction are greater, while coupling of glucose oxidation to glycolysis is lower in hypertrophied hearts than in nonhypertrophied hearts. OBJECTIVE: To test the hypothesis that accelerated glycolysis, reduced coupling of glucose oxidation to glycolysis and increased postischemic dysfunction in hypertrophied hearts compared with nonhypertrophied hearts occur in the absence of differences in coronary flow. MATERIALS AND METHODS: Function, glycolysis and glucose oxidation were measured in isolated working control and hypertrophied rat hearts studied for 30 min before, and for 40 min after no flow global ischemia for 20 min under conditions in which coronary flow was comparable between the two groups. The hearts were perfused with 1.2 mmol/L palmitate, 5.5 mmol/L [5-3H/U-14C]-glucose, 0.5 mmol/L lactate, 100 mU/L insulin at a preload of 11.5 mmHg, and an afterload of 60 mmHg in control hearts or 80 mmHg in hypertrophied hearts. RESULTS: Despite comparable rates of coronary flow, functional recovery was lower in hypertrophied hearts than in control hearts. The rates of glycolysis were accelerated in hypertrophied hearts, while glucose oxidation did not significantly differ between the two groups. As a result, the coupling of glucose oxidation to glycolysis was lower in hypertrophied hearts than in control hearts. CONCLUSIONS: Increased postischemic dysfunction, accelerated glycolysis and reduced coupling of glucose oxidation to glycolysis in hypertrophied hearts compared with control hearts cannot be accounted for by differences in coronary flow. These data provide support for the concept that alterations in glucose metabolism contribute to the exaggerated postischemic dysfunction of hypertrophied hearts.

Animals↗
PubMed2000

Electrical remodeling of membrane ionic channels of hypertrophied ventricular myocytes from spontaneously hypertensive rats.

OBJECTIVE: To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes. METHODS: Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole-cell configuration of patch-clamp technique, with normal Wistar rats ventricular myocytes as controls. We observed depolarizing currents (sodium current, INa; L-type calcium current, L-ICa) and repolarizing currents (inward rectifier potassium current, IK1; delayed rectifier potassium current, IK; transient outward potassium current, Ito) and compared the differences between normal and hypertrophied myocytes. RESULTS: The heart to body weight ratio of Wistar rats and SHRs was 3.70 +/- 0.29 mg/g and 5.66 +/- 0.46 mg/g, respectively (P < 0.001), and the mean cell membrane capacitances were 189.94 +/- 56.59 pF and 280.68 +/- 67.98 pF, respectively (P < 0.05). These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes. The amplitude of L-Ica of SHRs (1944 +/- 466.8 pA) was significantly greater than that of Wistar rats (1136 +/- 383.3 pA) (P < 0.001), and the current density was 6.93 +/- 1.71 pA/pF and 6.19 +/- 2.85 pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56.01 +/- 13.36 ms vs 43.63 +/- 17.89 ms, P < 0.001). The amplitude of INa of SHRs (6132.5 +/- 1162.9 pA) was significantly greater than that of Wistar rats (3613.9 +/- 794.44 pA) (P < 0.001), but there was no difference when normalized to cell capacitance (24.61 +/- 6.72 pA/pF vs 24.95 +/- 6.99 pA/pF). Channel activation and inactivation time constants were also the same. The amplitude of IK of SHRs (3461.5 +/- 1967.10 pA) was greater than that of Wistar rats (2302.4 +/- 893.72 pA) (P < 0.05), but there was no difference when normalized to cell capacitance (12.38 +/- 5.46 pA/pF vs 11.86 +/- 3.59 pA/pF). The inward portion of IK1 of SHRs was significantly lower than that of Wistar rats (11.3 +/- 2.26 pA/pF vs 14.3 +/- 3.00 pA/pF, P < 0.05), but there was no difference in the outward portion (2.360 +/- 0.86 pA/pF vs 2.957 +/- 1.27 pA/pF). The current density of Ito of SHRs (8.21 +/- 6.64 pA/pF) was significantly lower than that of Wistar rats (19.16 +/- 6.17 pA/pF) (P < 0.001), but channel kinetics were similar, suggesting that the reduction of Ito may result from the decrease in channel number. CONCLUSIONS: Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1. there was an increase of L-Ica, INa and Ik, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2. Ito was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge. The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of Ito may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity. Therefore, the reduction of Ito in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling.

Animals↗
PubMed1995

Experimental evidence for effects of ramipril on cardiac and vascular hypertrophy beyond blood pressure reduction.

In renal hypertensive rats with pressure overload left ventricular hypertrophy the angiotensin converting enzyme inhibitor ramipril, given in a high blood pressure lowering dose as well as in a low, non-antihypertensive dose, prevented and regressed left ventricular hypertrophy. These beneficial effects were abolished by coadministration of the specific bradykinin receptor antagonist (HOE 140) in the prevention--but not in the regression studies. Vascular function of rats with pressure overload left ventricular hypertrophy was impaired, whereas treated animals showed a reversal to normal. The angiotensin II subtype AT1 receptor antagonist, losartan, was barely active in the prevention, however markedly active in the regression of left ventricular hypertrophy. From these experimental studies in rats with pressure overload left ventricular hypertrophy and vascular dysfunction we conclude that inhibition of bradykinin degradation induced by ramipril may contribute to the antihypertrophic action during the prevention phase, whereas attenuation of angiotensin II formation may be more important during the regression period. In another model, the spontaneously hypertensive rat (SHR and stroke prone SHR)--a non-renal hypertensive model--cardiac left ventricular hypertrophy could be reduced by chronic high-dose ramipril treatment in prevention and regression studies, whereas the low dose regimen only reduced left ventricular hypertrophy in the regression experiments. In addition, both doses improved the myocardial capillary supply to the heart leading to improved function and metabolism. In comparison, vascular hypertrophy of the mesenteric artery could only be prevented by early-onset high dose treatment with the angiotensin converting enzyme inhibitor but not once hypertrophy has been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Experimental study and clinical observations on hypertrophy of vascularized bone grafts.

In order to understand the mechanisms involved in the hypertrophy of vascularized bone grafts, a series of animal experiments were carried out and 32 clinical cases were studied. A defect in the tibial shaft was created in puppies and the ipsilateral fibula was transferred into the medullary cavity of the tibia with the anterior tibial artery and vein. The same procedure was performed on a control group but without vessel supply. Radiologically, in the vascularized group mild hypertrophy in the fibula was seen at 2 weeks, became marked by 4 weeks, but in no case did the thickening (hypertrophy) of the graft ever exceed the diameter of the recipient tibia. The control group did not show hypertrophy but fracture callus formed in the recipient tibia at both ends of the graft. On histological evaluation no reactive bone formation was evident in the control group but some reactive bone formation was seen in the vascularized group just beneath the periosteum. There was no change in the periosteum itself. In the clinical cases 47% of patients showed hypertrophy. Hypertrophy was noted mainly in the fibulae but rarely in other bones such as ilium or rib. The important factors were age and good vascularity of the grafted bone. During the period of study, weight-bearing was eliminated, so that the effects of mechanical force did not explain hypertrophy. We conclude from these studies that true hypertrophy is an essentially different process from reactive callus which forms normally in response to fracture healing. Vascularized bone grafts show remarkable hypertrophy of the grafted bone, but the exact mechanism is ill defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Diastolic dysfunction in pressure-overload hypertrophy and its modification by angiotensin II: current concepts.

Cardiac hypertrophy is an adaptive response to an increased load imposed on the myocyte which allows the heart to perform increased work while maintaining normal myocardial fiber stress and shortening in systole. A deleterious consequence of pressure-overload hypertrophy is the prolongation of Ca(2+)-sensitive force inactivation (impaired myocardial relaxation) which is related to intrinsic alterations in cytosolic Ca2+ transport and reuptake in diastole. Additional factors appear to adversely modify myocardial relaxation in the hypertrophied heart, including the imposition of ischemia. There is also evidence that the expression and activity of the cardiac tissue renin angiotensin system (RAS) may be modified in the hypertrophied heart and contribute to diastolic dysfunction. Recent studies have demonstrated the presence of increased cardiac angiotensin converting enzyme (ACE) mRNA expression and activity in animal models of hypertrophy, including the aortic-banded rat with compensatory pressure-overload hypertrophy and rats with post-infarction remodeling. In the beating, isovolumic aortic-banded rat heart, the increased intracardiac activation of angiotensin I to II has been shown to be associated with a dose-dependent depression of diastolic relaxation. Preliminary studies suggest that the depression of diastolic function by angiotensin II in the hypertrophied heart can be prevented by the specific inhibition of cardiac ACE. In addition, the well-recognized susceptibility of the hypertrophied heart to severe ischemic diastolic dysfunction also appears to be favorably modified by the inhibition of cardiac ACE activity. The mechanisms responsible for the adverse effects of angiotensin II on diastolic relaxation in the hypertrophied heart are likely to be complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Morphological reaction patterns in experimental cardiac hypertrophy--a quantitative stereological study.

Four experimental models of myocardial hypertrophy were investigated in rats: 1. Mild hypertrophy induced by physical exercise, 2. mild hypertrophy induced by chronic pressure overload (24 weeks), 3. moderate hypertrophy induced by chronic pressure overload (8 weeks), 4. moderate hypertrophy in diabetes induced by chronic pressure overload (8 weeks). Stereological investigations on left ventricular papillary muscles disclosed different morphological reaction patterns: 1. The capillary bed of the myocardium responded differently in mild hypertrophy:physical training, but not mild chronic pressure overload, evoked neoformation of capillaries. 2. Mild hypertrophy and moderate hypertrophy induced by chronic pressure overload were not associated with quantitative structural reactions of myofibrils and mitochondria. Those alterations appeared, however, in hypertensive-diabetic rats with moderate hypertrophy. Our data provide further experimental evidence for the existence of a hypertensive-diabetic cardiomyopathy.

Animals↗
PubMedDate not supplied

Myocardial contractility and ventricular myosin isoenzymes as influenced by cardiac hypertrophy and its regression.

Changes in myocardial contractility and ventricular myosin isoenzymes were examined during pressure-overloaded cardiac hypertrophy in rats. Effects of regression of cardiac hypertrophy were also examined. Cardiac hypertrophy was induced by abdominal aortic constriction in 7-week-old male Wistar rats. Regression of cardiac hypertrophy was obtained by opening the aortic band. Myocardial contractility was estimated by measuring isometrically developed tension and maximum rate of tension rise (+dT/dtmax) in isolated left-ventricular papillary muscles perfused with Tyrode solution (32 degrees C, pH 7.4, bubbled with 95% O2.5% CO2, stimulation frequency: 0.2 Hz). Left-ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis and the isoenzyme pattern was determined by densitometry. Isometrically developed tension (T) in hypertrophic myocardium remained unchanged, but +/-dT/dtmax decreased as compared with hearts of normal rats. Decreased +/-dT/dtmax recovered near to the level in normal rats by regression of cardiac hypertrophy. Left-ventricular myosin isoenzyme pattern shifted towards VM-3 in hypertrophied myocardium and shifted again toward VM-1 by regression of cardiac hypertrophy. In conclusion, myocardial contractility and ventricular myosin isoenzymes were changed in pressure-overloaded hypertrophy in rats and these changes were reversible to a normal level by regression of cardiac hypertrophy.

Animals↗
PubMed1993

Enhanced functional expression of transient outward current in hypertrophied feline myocytes.

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch voltage-clamp studies designed to explain these changes in the action potential suggest that the only component of the membrane current recorded from feline right ventricular (RV) myocytes found to be substantially different from normal is the 4-amino-pyridine-sensitive transient outward current (I(to)). However, it was not clear if the change in I(to) could explain the changes in the action potential of hypertrophied cardiocytes, nor was it clear if these changes reflect an alteration in the electrophysiological character of the channels underlying I(to). A kinetic comparison of I(to) elicited by hypertrophied RV myocytes with that elicited by comparable normal RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak I(to) recorded from hypertrophied myocytes arises because the current density increases and not because of any alteration in the kinetic parameters governing the current. This finding suggests that in hypertrophy additional normal channels are expressed rather than a kinetically different channel subtype emerging. Investigations designed to determine if enhancement of I(to) could explain the hypertrophy-induced changes in plateau voltage and action potential duration suggest that a change in I(to) density can indeed explain the entire effect of hypertrophy on RV action potentials. If this notion is correct, the likelihood of "sudden death" in patients with myocardial hypertrophy might be decreased by a blocker selective for cardiac I(to).

Action Potentials↗
PubMed1991

Architecture of myocardial cells in human cardiac ventricles with concentric and eccentric hypertrophy as demonstrated by quantitative scanning electron microscopy.

Scanning electron microscopy (SEM) was used to compare the shapes, size, and connections of cardiocytes in the midwall myofibers in the left ventricles of 5 normal hearts (266 +/- 16 g), 5 hears with concentric hypertrophy (564 +/- 99 g) and 5 with eccentric hypertrophy (651 +/- 114 g), obtained at autopsy and fixed in formalin. In the myofibers from normal and hypertrophied hearts, intercalated discs demarcated cardiocytes which consisted of a cylindrical trunk and one or more series and/or lateral branches; cell connections at the intercalated discs had 6 common basic patterns. The length (L), width (W) and L/W ratio of the cells and the size and number of the series and lateral branches per cell were measured in 50 cells from each heart and averaged for comparison studies. The cells in the concentrically hypertrophied ventricles were much thicker than normal (33.0 +/- 2.8 vs 18.2 +/- 1.4 microns, P less than 0.01) but not significantly longer (81.2 +/- 9.5 vs 71.2 +/- 9.6 microns, NS), so that the L/W ratio was greatly decreased (2.6 +/- 0.3 vs 4.1 +/- 0.7, P less than 0.01). The cells in the eccentrically hypertrophied ventricles were markedly thickened (25.9 +/- 2.4 microns, P less than 0.01) and elongated (4.2 +/- 0.4, NS) remained the same as in normal hearts. In both types of hypertrophy, series and lateral branches were significantly thicker and longer than in normal hearts; the number of series branches per cell was also significantly increased. The number of lateral branches per cell did not differ between the normal and concentrically hypertrophied hearts (2.2 +/- 0.7 vs 2.3 +/- 0.6, NS), but it was decreased by approximately one-half in the eccentrically hypertrophied hearts (1.2 +/- 0.3, P less than 0.05). The potential significance of these differences in SEM findings of cardiocytes is discussed with special reference to the differences in the cause, anatomy, and pathophysiology of concentric and eccentric hypertrophy in adult human hearts.

Adult↗
PubMed1991

Altered pattern of post-rest contractions in hypertrophied rabbit ventricle.

The pattern of contractions elicited after rest periods of 0.25-10 min duration was investigated in right ventricular papillary muscles from control and hypertrophied rabbit hearts. Hypertrophy was induced by pressure overload following coarctation of the pulmonary artery. In control hearts, the first post-rest contraction was always of a smaller amplitude than the preceding steady-state (0.5 Hz stimulation) contractions, and the amplitude of this first post-rest contraction decreased as the rest interval increased. In contrast, the amplitude of the first post-rest contraction of muscles from hypertrophied hearts exceeded the steady-state amplitude for rest durations of up to at least 2 min. In the hypertrophied muscles, force in the first post-rest contraction (expressed as a percentage of the pre-rest steady-state) was potentiated compared to the control muscles at all rest intervals studied. There was no significant difference in the second post-rest contraction between control and hypertrophied muscles at any rest interval. Following the second post-rest contraction, force increased monotonically toward the steady-state levels in all the muscles. The recovery of force was, however, somewhat faster in the hypertrophied muscles. Upon resumption of 1-Hz stimulation following rest intervals of 2 min or greater, pulsus alternans were invariably observed in the hypertrophied muscles but never in the control muscles. These differences in the non-steady-state contractile behavior of ventricular muscle from normal and hypertrophied hearts are suggestive of some alteration in the normal pattern of Ca2+ translocation in pressure overload hypertrophy of rabbit ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Reduced myocardial injury due to exogenous oxidants in pressure induced heart hypertrophy.

Changes in myocardial function, structure, high energy phosphates and lipid peroxide content were examined in hypertrophied hearts exposed to partially reduced forms of oxygen (PRFO) in an ex vivo system. Heart hypertrophy in rats was produced by narrowing of the abdominal aorta for 6, 12, 24, and 48 weeks. During this period, a stable hypertrophy and hyperfunction with no clinical signs of heart failure is reported to be accompanied by an increase in myocardial superoxide dismutase and glutathione peroxidase activities and a decrease in lipid peroxide content (Gupta and Singal, Circ. Res. 64:398-406, 1989). A 10-min perfusion of sham control hearts with PRFO caused a significant decline in the developed force, +/- dF/dt and a rise in resting tension. These changes due to PRFO were significantly less in all groups of hypertrophied hearts. PRFO produced 80.8 +/- 4.2% increase in malondialdehyde (MDA) content in sham controls, while different groups of hypertrophied hearts showed significantly lesser increase (range 45-50%) in MDA. PRFO resulted in loss of myocardial ATP and CP in control and hypertrophied groups, but this loss was significantly less in all groups of hypertrophied hearts. Both quantitative and qualitative ultrastructural changes due to PRFO were also found to be less in hypertrophied hearts. There were no significant differences among 6- to 48-week hypertrophy groups in their response to PRFO. The study suggests that endogenous antioxidants may serve as putative stabilizers of myocardial subcellular as well as contractile functions against oxidative stress.

Adenosine Triphosphate↗
PubMed2004

Calcineurin independent development of myocardial hypertrophy in transgenic rats overexpressing the mouse renin gene, TGR(mREN2)27.

Myocardial hypertrophy is an independent risk factor for development of heart failure. The intracellular calcium homeostasis is altered in myocardial hypertrophy, and recent studies in animal models have confirmed an interaction between the Ca2+/calmodulin-dependent calcineurin signaling cascade and development of cardiac hypertrophy. There is evidence for the involvement of various pathways in development of hypertrophy. A transgenic rat model overexpressing the mouse renin gene, TGR(mREN2)27 has been shown to progress profound cardiac hypertrophy, possibly due to a monogenetic disorder. However, the exact mode of action is not known. To study a possible involvement of calcineurin and its downstream pathway in development of cardiac hypertrophy in this transgenic rat model we measured the protein expression of marker proteins of the calcineurin cascade (calcineurin, NFAT-3, GATA-4) and calcineurin phosphatase activity and GATA-4 DNA binding in TGR ( n=10) compared to age-matched Sprague-Dawley rats ( n=10). In our study there was no significant difference in calcineurin activity between the transgenic hearts and the hearts of Sprague-Dawley rats. Furthermore, we found neither an increase in protein expression of calcineurin B nor a rise in nuclear translocated NFAT-3 DU. Interestingly, the protein expression of GATA-4 and its DNA binding activity were significantly higher in hypertrophied myocardium than in control hearts. In transgenic rats overexpressing the mouse renin gene and thereby developing pronounced cardiac hypertrophy [TGR(mREN2)27] we thus found no activation of calcineurin or its downstream pathway. However, the expression of the transcriptional factor GATA-4 and its DNA binding activity were significantly increased in hearts of transgenic rats. Thus GATA-4 seems to be a marker of hypertrophy independently of calcineurin activation, possibly activated by various pathways.

Animals↗
PubMed1984

Recognition of regional hypertrophy in hypertrophic cardiomyopathy using thallium-201 emission-computed tomography: comparison with two-dimensional echocardiography.

The configuration of the hypertrophied myocardium was evaluated by thallium-201 emission-computed tomography and 2-dimensional (2-D) sector scan in 10 patients with obstructive hypertrophic cardiomyopathy (HC), 10 with nonobstructive HC with giant negative T waves and 10 with concentric left ventricular (LV) hypertrophy. Thallium-201 myocardial imaging was reconstructed into multiple 12-mm-thick slices in 3 planes. The thickness ratio of the ventricular septum and the LV posterior wall in the short-axis plane and the ratio of the ventricular septum and the apical wall in the long-axis plane were analyzed. In the patients with obstructive HC the ventricular septal wall thickness index was increased, and the ratio of septal to posterior wall thickness index (1.45 +/- 0.23) was greater than that in the patients with nonobstructive HC with giant negative T waves or in those with concentric LV hypertrophy (1.03 +/- 0.20 and 0.98 +/- 0.11, respectively; p less than 0.01 for each). In the patients with nonobstructive HC with giant negative T waves, increased apical wall thickness with apical cavity obliteration was characteristic, and the ratio of ventricular septal to apical wall thickness index (0.66 +/- 0.14) was less than that in the patients with obstructive HC or in those with concentric LV hypertrophy (1.46 +/- 0.38 and 1.04 +/- 0.09, respectively; p less than 0.001 for each). In contrast, technically satisfactory 2-D sector scanning (83%) demonstrated various configurations of the hypertrophied ventricularseptum, but could not detect apical hypertrophy in 4 of the 10 patients with nonobstructive HC with giant negative T waves whose LV cineangiograms demonstrated apical hypertrophy. Thus, thallium-201 emission-computed tomography is useful in evaluating the characteristics of LV hypertrophy and assists 2-D sector scan, especially in patients with apical hypertrophy in HC.

Adult↗
PubMed1987

Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study.

The association of ventricular arrhythmias with left ventricular (LV) hypertrophy was examined in 6,218 participants in the Framingham Heart Study. Electrocardiographic (ECG) LV hypertrophy was present in 171 subjects and echocardiographic hypertrophy was detected in 869. Echocardiographic LV hypertrophy was associated with increased risk for each of 6 ventricular arrhythmia grades in men (relative risk up to 8.9, p less than 0.01), and 4 of 6 grades in women (p less than 0.05). Similarly, men with ECG LV hypertrophy were at increased risk for 4 of 6 arrhythmia grades (p less than 0.05). However, owing to low prevalence ECG LV hypertrophy was not associated with arrhythmia in women. After adjustment for age, sex, systolic blood pressure, valvular heart disease, angina pectoris and acute myocardial infarction, the association of echocardiographic but not ECG LV hypertrophy with ventricular arrhythmia remained significant (p less than 0.001). Thus, echocardiographic LV hypertrophy is more prevalent and more sensitive for ventricular arrhythmias than ECG LV hypertrophy.

Adult↗
PubMed1987

Left ventricular hypertrophy, arrhythmias and sudden death in systemic hypertension.

Left ventricular (LV) hypertrophy is a significant independent risk factor for mortality from coronary heart disease, including sudden death. The proportion of sudden death to total death due to coronary heart disease remains high, at about 50% to 60%, despite the continuing downward trend in coronary heart disease mortality observed in the U.S. during the last decade. Prevalence of LV hypertrophy, determined by electrocardiogram in hypertensive patients (diastolic blood pressure greater than or equal to 90 mm Hg), including tall R wave and evidence of repolarization abnormality, is around 5%. The prevalence of LV hypertrophy by echocardiography is estimated at 44% to 48%. LV hypertrophy on electrocardiogram underestimates the magnitude of the problem of LV hypertrophy in hypertensive patients. Its overall sensitivity is less than 60%. The incidence of LV hypertrophy in hypertensive patients is lower when hypertension is treated successfully than when the patient is left either untreated or inadequately treated; successful treatment of hypertension causes regression of LV hypertrophy. However, hypertensive patients with LV hypertrophy have a poor prognosis despite treatment. The available evidence derived from the results of large clinical trials suggests that hypertensive patients should be treated before there is electrocardiographic evidence of LV hypertrophy.

Adult↗