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PubMed1999

The impact of different echocardiographic diagnostic criteria on the prevalence of left ventricular hypertrophy in essential hypertension: the VITAE study. Ventriculo Izquierdo Tension Arterial España.

BACKGROUND: The prevalence of echocardiographic left ventricular hypertrophy in essential hypertension ranges from 12 to 96% depending on the threshold values used to define it, and on the selection bias. OBJECTIVE: To estimate the prevalence of echocardiographic left ventricular hypertrophy by different criteria in essential hypertensives seen in primary care centres. METHODS: Cross-sectional study in a population-based sample of 946 essential hypertensives randomly selected in 39 primary care centres across Spain. Echocardiographic studies were performed in reference hospitals by trained observers (concordance Cohen kappa index > 0.7) and analysed by a single observer. RESULTS: Prevalence of left ventricular hypertrophy ranged from 59.2% [95% confidence interval (CI) 56.1 -62.3] by Framingham criteria to 72.7% (95% CI 69.9-75.6) using the criteria of De Simone et al. (J Am Coll Cardiol 1995; 25: 1056-1062). Prevalence was higher in males by the Cornell-Penn criteria, but higher in females when using Framingham or De Simone et al. criteria. Eccentric hypertrophy was more frequent (51.3-54.1%) independently of the criteria used, particularly when adjusting wall-thickness-ratio for age (56.2-58.9%). Concentric remodelling was present in 6.5-11.4% and only 20.8-29.7% of patients had no evidence of left ventricular structural alterations. Factors independently associated with left ventricular hypertrophy in the logistic regression analysis were age, gender, systolic blood pressure, pulse pressure and body mass index. CONCLUSION: Prevalence of echo left ventricular structural alterations among essential hypertensives seen in primary care centres in Spain ranged from 70.3 to 79.2% depending on the threshold values used. Left ventricular hypertrophy ranged from 59.2 to 72.7% and age-adjusted concentric remodelling ranged from 6.5 to 11.4% depending on the criteria used. Only one-quarter of hypertensive patients were free from morphological alterations.

Aged↗
PubMed2000

Left ventricular wall stresses and wall stress-mass-heart rate products in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint reduction in hypertension.

OBJECTIVE: Left ventricular (LV) hypertrophy on echocardiogram (ECG) strongly predicts coronary heart disease events, but the mechanisms linking increased LV mass to ischemic vascular events is uncertain. DESIGN: Variables related to myocardial oxygen demand were compared among normotensive adults and patients with mild and more severe hypertension, and among groups of moderately hypertensive patients with target organ damage in relation to gender, LV geometry and LV systolic function. SETTING: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, in which hypertensive patients with ECG LV hypertrophy (Cornell voltage-duration product, > 2440 mm x ms and/or SV1 + RV(5-6) > 38 mm) were randomized to > or = 4 years double-blinded treatment with losartan or atenolol. PATIENTS/PARTICIPANTS: A total of 964 LIFE participants enrolled in an echocardiographic substudy, and groups of 282 employed hypertensive and 366 apparently normal adults. INTERVENTIONS: None. MAIN OUTCOME MEASURES: ECG LV parameters contributing to myocardial oxygen demand (wall stresses, LV mass, heart rate and wall stress-mass-heart rate products). RESULTS: In both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall stresses, mass and stress-mass-heart rate products. LIFE men patients had slightly higher wall stresses and significantly higher triple products than women. Wall stresses were increased in patients with normal LV geometry, eccentric or concentric hypertrophy; triple products were about three and two times normal with eccentric and concentric hypertrophy, with smaller increases in other geometric groups. Patients with decreased LV fractional shortening had two times normal end-systolic stresses and three or four times normal triple products; smaller increases in stresses and triple products occurred with decreased LV midwall function. CONCLUSIONS: Hypertensive patients with ECG LV hypertrophy have increased LV wall stresses and stress-mass-heart rate products, suggesting a contribution of high myocardial oxygen demand to increased risk in such patients. Particularly high stresses and triple products were associated with echocardiographic LV hypertrophy, and subnormal LV chamber and midwall function.

Adult↗
PubMed2004

Cardiovascular hypertrophy in one-kidney, one-clip renal hypertension is resistant to heparin.

OBJECTIVE: Heparin inhibits vascular hypertrophy in angiotensin-induced hypertension, in addition to its well-known role in inhibiting injury-induced vascular smooth muscle proliferation. We tested whether hypertension and vascular hypertrophy could be reduced by heparin independently from the renin-angiotensin system. METHODS: Rats were made hypertensive with a one-kidney, one-clip (1K1C) procedure and received heparin from osmotic minipumps (0.3 mg/h per kg i.v.) or saline vehicle for 2 weeks. Blood pressure was measured by the tail-cuff method and vessel cross-sectional area was measured by morphometry in the aorta and mesenteric arteries. Proliferation was assessed with bromodeoxyuridine labelling. RESULTS: Blood pressure elevation and cardiovascular hypertrophy were evident in 1K1C rats. The media of mesenteric arteries was increased by 25%, and the media : lumen ratio by 35%, in hypertensive rats. DNA synthesis by smooth muscle cells in the mesenteric arteries was increased sevenfold in renal hypertension. Heparin treatment did not influence either the increase in blood pressure, the cardiovascular hypertrophy response or hypertension-mediated proliferation of arterial smooth muscle cells. CONCLUSIONS: These data suggest that the vascular hypertrophy mechanisms operating in 1K1C renal hypertension are not inhibited by heparin and thus are different from those in angiotensin-mediated hypertension. Identifying such mechanisms in the future will be important for devising appropriate intervention strategies in angiotensin-independent forms of vascular hypertrophy.

Angiotensin II↗
PubMed2001

Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: an echocardiographic study.

The objective of this study was to evaluate, using echocardiography, the involvement of the renin-angiotensin system (RAS) in left ventricular (LV) hypertrophy development in experimental hyperthyroidism. Thyrotoxicosis was produced by a daily intraperitoneal injection of L-thyroxine (T4), 0.1 mg/kg per day for 15 days in Wistar rats. Control (euthyroid) rats received intraperitoneal daily injection of the thyroxine solvent. Two series of experiments were performed. In the first series, euthyroid (n = 10) and hyperthyroid (n = 14) rats were surgically prepared with a femoral artery catheter. After a 3-day recovery period, blood pressure and heart rate were measured and blood samples were collected in conscious and unrestrained rats. In the second series of experiment, measurement of LV geometry was realized with two-dimensional time-movement echocardiography on the 15th day of treatment in control conditions and after long-term treatment with the angiotensin II type I receptor antagonist valsartan (10 mg/kg per day for 15 days) in both euthyroid and hyperthyroid rats. The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a threefold increase in plasma renin activity. Echocardiographic examinations in rats revealed a strong correlation between LV weight and echocardiographic LV mass. Hyperthyroid rats exhibited an increased LV mass with a marked increase in the LV end-diastolic posterior wall and septal thickness. Chronic treatment with valsartan prevented this concentric LV hypertrophy (p < 0.01), with full prevention of the LV posterior wall hypertrophy (p < 0.001) and decreased LV septal hypertrophy (p < 0.05). In conclusion, the cardiovascular alterations of hyperthyroidism were reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased LV mass. Using valsartan, we demonstrated that the RAS impinged on the LV remodelling in our experimental hyperthyroidism model. A chronic treatment with an angiotensin II type I receptor antagonist prevented the development of the concentric LV hypertrophy associated with thyrotoxicosis.

Animals↗
PubMed2001

Hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification: a cervical myelopathy case report.

STUDY DESIGN: A histopathologic examination of a specimen that showed hypertrophy of the posterior longitudinal ligament of the cervical spine. OBJECTIVES: To illustrate the possibility of hypertrophy of the posterior longitudinal ligament as a prodromal condition to ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Despite much study, the pathology of ossification of the posterior longitudinal ligament still remains unclear. Hypertrophic change often is seen in the part of the ossified ligament; however, there have been few histopathologic reports on hypertrophy of the posterior longitudinal ligament. Some reports have suggested that hypertrophy of the posterior longitudinal ligament is a prodrome of ossification of the posterior longitudinal ligament. METHODS: A 64-year-old man was admitted to the hospital because of gait disturbance and developed oliguria. In a plain radiograph, segmental ossification of the posterior longitudinal ligament was found at C4, C5, and C6. Computed tomograph myelogram revealed a soft tissue shadow, maximum 3.8 mm in diameter, on the dorsal side of the ossification of the posterior longitudinal ligament at C5 and C6. Magnetic resonance T1-weighted image (T1WI) showed an equivalent signal with the intervertebral disc on the dorsal side of ossification of the posterior longitudinal ligament. This lesion was enhanced with Gd-DTPA and confirmed as hypertrophy of the posterior longitudinal ligament. Cervical anterior decompression and fusion were performed using Yamaura's technique. The ossified and thickened lesion was elevated and removed en bloc. Then, hematoxylin-eosin and toluidine blue staining was performed to detect metachromasia. RESULTS: Macroscopic examination of the specimen revealed that soft tissue formation was connected with the C4-C5 intervertebral space and extended downward to C6-C7. Histopatholgically, collagen fibers were proliferating in the long-axis direction on both ventral and dorsal sides. This was surrounded by extended nucleus pulposus-like chondrocyte tissue, where endplate cartilage was detected around the C4 pedicle. Roux staining was low, and partial vascular and cellular infiltration was observed, although it was not marked. CONCLUSION: The herniated nucleus pulposus involving endplate cartilage from C4-C5 was limited to the superficial layer, and proliferation of nucleus pulposus-like chondrocytes occurred in the herniated tissue, where they might undergo a change in cell phenotype. The results of the present study support the hypothesis that hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification of the posterior longitudinal ligament.

Cervical Vertebrae↗
PubMed2004

Exogenous attenuation of p21(Waf1/Cip1) decreases mesangial cell hypertrophy as a result of hyperglycemia and IGF-1.

Renal mesangial cell hypertrophy is a characteristic of diabetic nephropathy as well as a response to renal stress or injury. Because hypertrophy is a result of increased protein content per cell without DNA replication, those proteins that control the cell cycle, such as the cyclin kinase inhibitor p21, represent fertile ground for studying the mechanism of this structural alteration. A key role for p21 in promoting mesangial cell (MC) hypertrophy has been established using p21 knockout mouse models. Furthermore, some of the biologic effects of IGF-1, including cell proliferation, have been shown to be positively influenced by p21. In an attempt to begin to translate these findings ultimately to the bedside, methods to attenuate p21 levels in wild-type kidney cells were examined. With the use of a phosphorothioated antisense oligodeoxynucleotide (ODN) to p21, which has previously been shown to decrease specifically and effectively p21 protein levels in a variety of cell types, it is shown that attenuation of p21 in MC leads to a dose-dependent reduction of hypertrophy in the milieu of hyperglycemic culture media. Furthermore, the hypertrophic effect of the IGF-1 on MC is also attenuated using the same antisense p21 ODN. There was no evidence of apoptosis or other toxicity in MC transfected with the concentrations of antisense p21 ODN used in these experiments. Because the use of antisense ODN in human disease is already established in other medical disciplines, the stage is now set for the use of antisense p21 ODN to attenuate renal cell hypertrophy in vivo, leading to a new strategy for treatment of diabetic nephropathy and other diseases characterized by MC hypertrophy.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed2004

Development, prevention, and potential reversal of left ventricular hypertrophy in chronic kidney disease.

Although a high prevalence of left ventricular (LV) hypertrophy is recognized with increasing severity of chronic kidney disease (CKD), previously neither its progression nor its potential for prevention or reversal has been addressed adequately in this population group. A nested analysis of a 2-yr study involving 155 patients with stage 3/4 CKD, examining effects of hemoglobin change (range, 90 to 130 g/L) on LV mass in patients with (n = 46; 30%) and without (n = 105; 70%) initial LV hypertrophy, is reported. At baseline, the group with LV hypertrophy was older (P < 0.01), had higher BP (P < 0.01), had greater LV wall and cavity dimensions (P < 0.001), and had more prevalent use of antihypertensive agents (P < 0.001) but a lower hemoglobin concentration (P < 0.05) and GFR (P < 0.01). A total of 117 patients were available for assessment at 2 yr. Importantly, 57 (68%) with initial normal LV indices showed no appreciable change with time; however, 27 (32%) developed LV hypertrophy, with growth in both wall and cavity dimensions (P < 0.001). In contrast, 23 (50%) of those with initial LV hypertrophy maintained elevated LV indices, whereas 10 (22%) regressed, through wall but not cavity reduction, to within normal LV indices. Predisposing factors to maintaining or achieving normal LV mass dimensions included relative youth (P < 0.05), a lower pulse pressure (P < 0.05), and a higher GFR (P < 0.05) but not hemoglobin concentration or parathyroid hormone levels. These findings suggest that even at a relatively advanced stage of renal dysfunction, control of BP and volume, together with regulated metabolic and clinical indices, may contribute to the prevention or even reversal of LV hypertrophy in a substantial proportion of patients.

Adolescent↗
PubMed2005

Irbesartan and atenolol improve diastolic function in patients with hypertensive left ventricular hypertrophy.

OBJECTIVES AND DESIGN: An abnormal diastolic filling is common in hypertensive left ventricular (LV) hypertrophy, a condition that may lead to heart failure and death. The renin-angiotensin-aldosterone system has been implicated in the development of LV hypertrophy. This study examines the effects of 48 weeks of double-blind treatment with the AT1 receptor blocker irbesartan and the beta-blocker atenolol on diastolic function. METHODS: Diastolic function was evaluated in 115 hypertensive patients with LV hypertrophy by Doppler echocardiography mitral inflow velocities calculated from the peak of early (E) and peak of late (A) diastolic velocities (E/A ratio), the E-wave deceleration time, the isovolumic relaxation time, the pulmonary venous flow velocity, and by the atrioventricular valve plane displacement method. RESULTS: By similar reductions in blood pressure both groups progressively reduced the LV mass index, with a greater reduction in the irbesartan group (P = 0.024). Diastolic function was improved similarly by irbesartan and atenolol; for example, the E/A ratio by 12 and 14% (P = 0.022 and P < 0.001), and the pulmonary venous flow velocity by 10 and 7% (P = 0.036 and P = 0.001), respectively. The isovolumic relaxation time was improved by irbesartan (P = 0.040) only, and was related to changes in LV geometry (P < 0.001). For atenolol, improvement in diastolic function was associated only with the reduction in blood pressure (P = 0.048). An improvement in diastolic function appeared greater in concentric LV hypertrophy than in eccentric LV hypertrophy. CONCLUSIONS: Treatment based on atenolol or irbesartan improves diastolic function in patients with hypertensive LV hypertrophy to the same degree, but through different mechanisms.

Adult↗
PubMedDate not supplied

Extent of hepatectomy on splenic hypertrophy and platelet count in live liver donors.

The extent of donor hepatectomy may affect splenic hypertrophy and platelet count. The subjects were 50 live liver donors. The ratio of the graft weight to total liver volume (GW/TLV) and the splenic hypertrophy ratio, expressed as the splenic volume one month after surgery divided by that before surgery, were calculated. The platelet count one month after surgery was divided by that before surgery to determine the rate of the platelet count decrease. The correlation of GW/TLV to the splenic hypertrophy ratio and the rate of the platelet count decrease were examined. The median (range) GW/TLV was 54 (28-71)%. The splenic hypertrophy ratio and the rate of the platelet count decrease was 133 (99-191)% and 92 (71-129)%, respectively. GW/TLV positively correlated with the splenic hypertrophy ratio (Spearman's correlation coefficient (r(s)) = 0.448, p = 0.001), and negatively correlated with the rate of the platelet count decrease (r(s) = -0.471, p < 0.001). Multivariate analysis revealed that GW/TLV influenced the splenic hypertrophy ratio [adjusted odds ratio (OR), 12.0; 95% confidence interval (CI), 1.32-9.04; p = 0.01] and the ratio of the platelet count decrease (adjusted OR, 11.6; 95% CI, 1.40-8.33; p = 0.01). Larger graft procurement might place living liver donors at higher risk for post-operative thrombocytopenia.

Body Weight↗
PubMed2004

Angiotensin converting enzyme inhibition for cardiac hypertrophy in patients with end-stage renal disease: what is the evidence?

Dialysis patients show a high prevalence of cardiovascular complications among which left ventricular hypertrophy is one of the most frequent and is independently predictive of mortality. A recent study indicates that partial regression of left ventricular hypertrophy improves mortality and reduces cardiovascular events in end-stage renal disease (ESRD) patients, suggesting the importance of targeting therapeutic strategies to reduce cardiac hypertrophy and improve the outcome in these patients. The pathogenesis of left ventricular hypertrophy in ESRD patients is multifactorial and includes hypertension, activation of the renin-angiotensin system, increased sympathetic activity, chronic volume overload, chronic anaemia and hyperparathyroidism. In this paper, we review the available experimental and clinical evidence showing the important contribution of the renin-angiotensin system as well as its interaction with the sympathetic nervous system in the pathogenesis of left ventricular hypertrophy in ESRD patients. Furthermore, we summarize the results of currently available clinical studies that examined the effects of angiotensin-converting enzyme inhibition or angiotensin receptor antagonism on left ventricular hypertrophy in ESRD patients, and review evidences that support the use of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists in the ESRD population.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Cultured tubule cells from TGF-beta1 null mice exhibit impaired hypertrophy and fibronectin expression in high glucose.

BACKGROUND: To firmly establish the role of the transforming growth factor-beta1 (TGF-beta1) isoform in the pathophysiology of diabetic tubulointerstitial hypertrophy and fibrosis, we examined how the total absence of TGF-beta1 would alter the effect of high glucose on cellular hypertrophy and matrix expression in tubuloepithelial cells cultured from TGF-beta1 null mice. METHODS: Primary tubule cell cultures, obtained from kidneys of TGF-beta1 knockout mice and their wild-type littermates, were treated with exogenous TGF-beta1 or high glucose. The TGF-beta system was characterized at the ligand and receptor levels using Northern and Western blotting. Cellular hypertrophy and growth were assessed by thymidine incorporation, cell counting, leucine incorporation, and protein content. Fibronectin expression was assessed by Northern analysis and enzyme-linked immunosorbent assay (ELISA). RESULTS: Knockout cells did not express TGF-beta1 but did express TGF-beta2, TGF-beta3, and TGF-beta type I and type II receptors. Exogenous TGF-beta1 down-regulated the ligand-binding type II receptor but up-regulated type I receptor expression. Knockout cells proliferated more rapidly than wild-type cells, but restoring TGF-beta1 to knockout cells slowed their proliferation. In wild-type cells, high glucose caused cellular hypertrophy, evidenced by greater leucine incorporation and protein content along with decreased thymidine incorporation. High glucose also increased fibronectin message and protein. However, in knockout cells, high glucose failed to induce hypertrophy and was severely limited in its capacity to stimulate fibronectin. CONCLUSION: In tubular epithelial cells, TGF-beta1 mediates the hypertrophic and fibronectin-stimulatory effects of high glucose, confirming the role of the TGF-beta1 isoform in the pathogenesis of diabetic tubular hypertrophy and fibronectin overexpression.

Activin Receptors, Type I↗
PubMed1994

QT interval dispersion in chronic heart failure and left ventricular hypertrophy: relation to autonomic nervous system and Holter tape abnormalities.

OBJECTIVE: To study QT dispersion in left ventricular hypertrophy and chronic heart failure and to determine the relation to ventricular arrhythmias. SETTING: Investigational laboratory of a tertiary referral centre. STUDY DESIGN: Patients with left ventricular hypertrophy and normal systolic function (n = 14) and patients with chronic heart failure (n = 18) were matched with controls (n = 17). The QT dispersion was examined in relation to abnormalities in resting mechanical and autonomic function and to the findings of 24 hour Holter monitoring. MAIN OUTCOME MEASURES: QT dispersion is the difference between the maximum and the minimum QT values from the 12 lead electrocardiogram. Mean(SD) QT dispersion from the 10 lead electrocardiogram was also examined once the 12 lead minimum and maximum values had been removed. The QT distribution is the curve describing the distance from the mean for all QT intervals (ms). RESULTS: All measures of QT dispersion were increased significantly in left ventricular hypertrophy and tended to increase in those with heart failure. The QT distribution was abnormal in both heart failure and left ventricular hypertrophy. There was no relation between the degree of change in QT dispersion and the incidence of ventricular arrhythmia on 24 hour Holter monitoring. Also there was no relation between QT dispersion and autonomic or mechanical abnormalities. The QT dispersion was related to QRS duration. CONCLUSION: Though QT dispersion and distribution are abnormal in left ventricular hypertrophy these findings do not support the hypothesis that QT dispersion reflects arrhythmic risk in either hypertrophy or heart failure.

Action Potentials↗
PubMed1991

Isolated muscle hypertrophy as a sign of radicular or peripheral nerve injury.

Two patients with isolated neurogenic hypertrophy of the trapezius muscle due to accessory nerve injury and a patient with neurogenic hypertrophy of the anterior tibial muscle due to chronic radicular lesion L4 are described. Electromyography of the affected muscles showed dense continuing spontaneous discharges of complex potentials. Muscle biopsy performed in two patients showed abundant hypertrophic muscle fibres, identified in one case by ATP-ase reaction as being of predominantly type I. In the majority of previously reported patients with neurogenic muscle hypertrophy confined to the calf muscle, a passive stretch mechanism was suggested as a cause of the hypertrophy. It is assumed that the excessive spontaneous muscle activity gave rise to the hypertrophy in these patients. This may also be true in previously reported patients with neurogenic hypertrophy and similar spontaneous activity in electromyography.

Adult↗
PubMed2005

Muscle hypertrophy models: applications for research on aging.

Muscle hypertrophy is an adaptive response to overload that requires increasing gene transcription and synthesis of muscle-specific proteins resulting in increased protein accumulation. Progressive resistance training (P(RT)) is thought to be among the best means for achieving hypertrophy in humans. However, hypertrophy and functional adaptations to P(RT) in the muscles of humans are often difficult to evaluate because adaptations can take weeks, months, or even years before they become evident, and there is a large variability in response to P(RT) among humans. In contrast, various animal models have been developed which quickly result in extensive muscle hypertrophy. Several such models allow precise control of the loading parameters and records of muscle activation and performance throughout overload. Scientists using animal models of muscle hypertrophy should be familiar with the advantages and disadvantages of each and thereby choose the model that best addresses their research question. The purposes of this paper are to review animal models currently being used in basic research laboratories, discuss the hypertrophic and functional outcomes as well as applications of these models to aging, and highlight a few mechanisms involved in regulating hypertrophy as a result of applying these animal models to questions in research on aging.

Adaptation, Physiological↗
PubMed2005

mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators.

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding factor (UBF). Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cyclin-dependent kinase (CDK)-4 activity toward Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, CDK-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D1-dependent CDK-4 activity in the regulation of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.

Animals↗
PubMed1982

Regression of skeletal muscle of chicken wing after stretch-induced hypertrophy.

Regression of stretch-induced growth of the anterior latissimus dorsi muscle of the adult fowl was characterized by measuring weight, protein, RNA, DNA, and collagen content. After 7 days of hypertrophy the total amount of protein, RNA, DNA, and collagen increased by 59, 228, 82, and 23%, respectively, above the control contralateral muscle. On removal of the stimulus, regression back to normal weight and composition was complete in 13 days except for total DNA content, which was still elevated 21% after 29 days of regression. After 28 days of hypertrophy, the total amount of protein, RNA, DNA, and collagen were 100, 126, 96, and 27%, respectively, greater than controls. On removal of the stimulus regression was again rapid, but reversal of the hypertrophy was not complete 35 days later with the total protein and RNA still elevated by 16-22% and the total DNA 35% above control level. The increase in the total collagen during hypertrophy was attributable to about equal increases in both the epimysial collagen and the internal collagen of the muscle. The study shows that reversal of hypertrophy can occur almost as rapidly as the hypertrophy process. RNA and protein are lost more rapidly than DNA.

Animals↗
PubMed1994

Redistribution of protein kinase C isoforms in association with vascular hypertrophy of rat aorta.

Freshly enzymatically isolated cells from the aorta of a rat model of vascular hypertrophy were used to investigate the role of protein kinase C (PKC) isoforms during a physiologically relevant growth response. With the combination of immunofluorescence with digital imaging microscopy, PKC isoforms alpha, delta, and zeta were found to be present in single cells from control and hypertrophied rat aortas. The alpha- and zeta-isoforms were distributed in the cytoplasm of control cells; however, in hypertrophied cells, sustained translocations of alpha-PKC to the surface membrane and zeta-PKC to the intranuclear area were seen. delta-PKC was concentrated in the perinuclear area in control cells but appeared to translocate to a more diffuse localization in the cytosol of hypertrophied cells. Staining of mitochondria with rhodamine 123 indicated some similarity in the spatial distribution compared with that of delta-PKC. In control cells, translocation of isoforms alpha and delta was activated by phenylephrine or 12-deoxyphorbol 13-isobutyrate 20-acetate. Agonist stimulation produced translocation of no isoforms in the hypertrophied cells. These results indicate that isoform-specific spatial distribution and translocation of PKC occur in association with the growth response of vascular hypertrophy.

Animals↗
PubMed2002

Accelerated rates of glycolysis in the hypertrophied heart: are they a methodological artifact?

Glycolysis, measured by (3)H(2)O production from [5-(3)H]glucose, is accelerated in isolated working hypertrophied rat hearts. However, nonglycolytic detritiation of [5-(3)H]glucose via the nonoxidative pentose phosphate pathway (PPP) could potentially lead to an overestimation of true glycolytic rates, especially in hypertrophied hearts where the PPP may be upregulated. To address this concern, we measured glycolysis using [5-(3)H]glucose and a second, independent method in isolated working hearts from halothane-anesthetized, sham-operated and aortic-constricted rats. Glycolysis was accelerated in hypertrophied hearts compared with control hearts regardless of the method used. There was also excellent concordance in glycolytic rates between the different methods. Moreover, activity of glucose-6-phosphate dehydrogenase and expression of transaldolase, enzymes controlling key steps in the oxidative and nonoxidative PPP, respectively, were not different between control and hypertrophied hearts. Thus nonglycolytic detritiation of [5-(3)H]glucose in the PPP is insignificant, and (3)H(2)O production from [5-(3)H]glucose is an accurate means to measure glycolysis in isolated working normal and hypertrophied rat hearts. Furthermore, the PPP does not appear to be increased in cardiac hypertrophy induced by abdominal aortic constriction.

Animals↗