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Biomedical subjects

E Fleck

Publications and source records attributed to E Fleck.

At least 37 records · Page 2Linked to original sources
PubMed2001

Transvenous biventricular defibrillation halves energy requirements in patients.

BACKGROUND: Defibrillation thresholds (DFT) with standard implantable cardioverter-defibrillator leads in the right ventricle (RV) may be determined by weak shock field intensity in the myocardium of the left ventricle (LV). Adding a shocking electrode in a coronary vein on the middle of the LV free wall, thereby establishing biventricular defibrillation, substantially reduced defibrillation requirements in animals. We investigated the feasibility of this approach in 24 patients receiving an implantable cardioverter-defibrillator using a prototype over-the-wire temporary LV defibrillation lead. METHODS AND RESULTS: The LV lead was inserted through the coronary sinus, using a guide catheter and guidewire, into a posterior or lateral coronary vein whose location was determined by retrograde venography. Paired DFT testing compared a standard system (RV to superior vena cava plus can emulator [SVC+Can], 60% tilt biphasic shock) to a system including the LV lead. The biventricular system was tested with a dual-shock waveform (20% tilt monophasic shock from LV-->SVC+Can, then 60% tilt biphasic shock from RV-->SVC+Can). Twenty patients completed DFT testing. Venography and LV lead insertion time was 46+/-40 minutes. The biventricular system reduced mean DFT by 45% (8.9+/-1.1 J versus 4.9+/-0.5 J, P<0.001). Twelve patients (60%) had a standard system DFT >/=8 J, and the biventricular system gave a lower DFT in all patients. There were no adverse events related to the use of the LV lead, which was removed after testing. CONCLUSIONS: Internal defibrillation using a transvenously inserted LV lead is feasible, produces significantly lower DFTs, and seems safe under the conditions tested. Biventricular defibrillation may be a useful option for reducing DFTs or could be added to an LV pacing lead for heart failure.

Coronary Angiography↗
PubMed2001

TNFalpha inhibits insulin's antiapoptotic signaling in vascular smooth muscle cells.

Tumor necrosis factor alpha (TNFalpha) interferes with insulin signaling in adipose tissue and may promote insulin resistance. Insulin resistance is associated with vascular injury, but little is known about the interaction of TNFalpha and insulin in the vasculature. By activating the Insulin receptor (IR) --> IRS-1 --> phosphatidylinositol-3-kinase (PI3K) --> Akt-pathway, insulin protects vascular smooth muscle cells (VSMC) from undergoing apoptosis. We therefore investigated the effect of TNFalpha on insulin's antiapoptotic signaling in rat aortic VSMC. Insulin induced rapid tyrosine-phosphorylation of the IR and IRS-1 and caused a 2.8-fold increase of IRS-1-bound PI3K. TNFalpha had no effect on insulin-induced tyrosine-phosphorylation of IR or IRS-1, but inhibited insulin-stimulated IRS-1/PI3K-association by 84%. Insulin-induced phosphorylation of Akt downstream of PI3K was inhibited by TNFalpha in a similar pattern. We next examined the effect of TNFalpha on insulin's protective actions on H(2)O(2)-induced apoptosis. Insulin alone prevented 72.8% of H(2)O(2)-induced apoptosis, which was significantly inhibited by TNFalpha. TNFalpha alone did not induce apoptosis. In contrast, TNFalpha had no effect on PDGF-induced antiapoptotic signal transduction via Akt. Thus, TNFalpha selectively interferes with insulin's antiapoptotic signaling in VSMC by inhibiting the association of IRS-1/PI3K and the downstream activation of Akt.

Animals↗
PubMed2001

Investigation of coronary venous anatomy by retrograde venography in patients with malignant ventricular tachycardia.

BACKGROUND: The coronary venous system is increasingly used for left ventricular or biventricular pacing in patients with severe heart failure. The present study investigated the structure of the coronary veins in patients presenting with structural heart disease and malignant ventricular tachyarrhythmias. The availability of veins for possible lead placement was assessed. METHODS AND RESULTS: The number, relative size, and location of coronary veins were evaluated by retrograde venography in 129 patients undergoing cardioverter-defibrillator implantation. Detailed x-ray image analysis was performed in 86 patients, for whom optimal coronary sinus occlusion and vein visualization was achieved. The anterior interventricular vein and the middle cardiac vein were visible in 85 (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these 2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86 patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were observed in 40 (46%) of 86 patients, and >2 veins were visualized in 2 (2%) of 86 patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a coronary vein in 115 (93%) of 124 patients. CONCLUSIONS: The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.

Aged↗
PubMed2001

The apoptotic regulatory protein ARC (apoptosis repressor with caspase recruitment domain) prevents oxidant stress-mediated cell death by preserving mitochondrial function.

ARC is an apoptotic regulatory protein expressed almost exclusively in myogenic cells. It contains a caspase recruitment domain (CARD) through which it has been shown to block the activation of some initiator caspases. Because ARC also blocks caspase-independent events associated with apoptosis, such as hypoxia-induced cytochrome c release, we examined its role in cell death triggered by exposure to hydrogen peroxide (H(2)O(2)) in the myogenic cell line, H9c2. Cell death in this model was caspase-independent and characterized by dose-dependent reduction in ARC expression accompanied by disruption of the mitochondrial membrane potential (Delta psi(m)) and loss of plasma membrane integrity, typical of necrotic cell death. Ectopic expression of ARC prevented both H(2)O(2)-induced mitochondrial dysfunction and cell death without affecting the stress kinase response, suggesting that ARCs protective effects were downstream of early signaling events and not due to quenching of H(2)O(2). ARC was also effective in blocking H(2)O(2)-induced loss of membrane integrity and/or disruption of Delta psi(m) in two human cell lines in which it is not normally expressed. These results demonstrate that, in addition to its ability to block caspase-dependent and -independent events in apoptosis, ARC also prevents necrosis-like cell death via the preservation of mitochondrial function.

Animals↗
PubMed2001

Intracellular energetic units in red muscle cells.

The kinetics of regulation of mitochondrial respiration by endogenous and exogenous ADP in muscle cells in situ was studied in skinned cardiac and skeletal muscle fibres. Endogenous ADP production was initiated by addition of MgATP; under these conditions the respiration rate and ADP concentration in the medium were dependent on the calcium concentration, and 70-80% of maximal rate of respiration was achieved at ADP concentration below 20 microM in the medium. In contrast, when exogenous ADP was added, maximal respiration rate was observed only at millimolar concentrations. An exogenous ADP-consuming system consisting of pyruvate kinase (PK; 20-40 units/ml) and phosphoenolpyruvate (PEP; 5 mM), totally suppressed respiration activated by exogenous ADP, but the respiration maintained by endogenous ADP was not suppressed by more than 20-40%. Creatine (20 mM) further activated respiration in the presence of ATP and PK+PEP. Short treatment with trypsin (50-500 nM for 5 min) decreased the apparent K(m) for exogenous ADP from 300-350 microM to 50-60 microM, increased inhibition of respiration by PK+PEP system up to 70-80%, with no changes in MgATPase activity and maximal respiration rates. Electron-microscopic observations showed detachment of mitochondria and disordering of the regular structure of the sarcomere after trypsin treatment. Two-dimensional electrophoresis revealed a group of at least seven low-molecular-mass proteins in cardiac skinned fibres which were very sensitive to trypsin and not present in glycolytic fibres, which have low apparent K(m) for exogenous ADP. It is concluded that, in oxidative muscle cells, mitochondria are incorporated into functional complexes ('intracellular energetic units') with adjacent ADP-producing systems in myofibrils and in sarcoplasmic reticulum, probably due to specific interaction with cytoskeletal elements responsible for mitochondrial distribution in the cell. It is suggested that these complexes represent the basic pattern of organization of muscle-cell energy metabolism.

Adenosine Diphosphate↗
PubMed2001

Aldosterone synthase (CYP11B2) -344 C/T polymorphism is associated with left ventricular structure in human arterial hypertension.

OBJECTIVES: This study examined the association between the -344 C/T polymorphism of the human aldosterone synthase promoter and left ventricular structure in arterial hypertension. BACKGROUND: Because of conflicting results from different studies, the mechanism of such an association, if any, has not been determined. METHODS: We examined the aldosterone synthase promoter genotype in 120 young (age: 26 +/- 3 years) male, white subjects with normal or mildly elevated blood pressure. Left ventricular structural parameters and urinary sodium excretion over 24 h before and after additional oral sodium load (6 g/day over 1 week) were determined. RESULTS: Hypertensive subjects with the CC genotype had a greater left ventricular end-diastolic diameter but smaller relative wall thickness than those with the TT genotype (54 +/- 2 vs. 50 +/- 4 mm, and 0.37 +/- 0.07 vs. 0.44 +/- 0.06 mm, respectively; p < 0.05). Hypertensive subjects with the TT genotype (n = 15) had a greater increase in urinary sodium excretion after oral sodium load than those with the CC genotype (n = 11) (135 +/- 95 vs. 24 +/- 133 mmol/liter/day; p < 0.05). Serum aldosterone levels were found to be decreased after oral sodium load in hypertensive subjects with the TT and CT genotypes only (-37 +/- 45 and -38 +/- 51 pg/ml, respectively; all p < 0.01) but not in those with the CC genotype (-12 +/- 30 pg/ml, n.s.). Such differences were not found in normotensive subjects. CONCLUSIONS: Hypertensive subjects with the -344 CC genotype of the aldosterone synthase promoter are characterized by a pattern of early eccentric left ventricular hypertrophy. Differences in renal sodium handling across the genotypes might contribute to this finding.

Adult↗
PubMed2001

Expression of CD40 in vascular smooth muscle cells and macrophages is associated with early development of human atherosclerotic lesions.

CD40-CD154-mediated signaling has recently been described as playing a role in cellular functions involved in atherosclerotic processes. CD40 is expressed in macrophages, lymphocytes, endothelial cells, and vascular smooth muscle cells. However, cross-sectional studies investigating the expression of CD40 in atherosclerotic lesions are lacking. In the present study the expression of CD40 was studied in atherosclerotic lesions from 43 patients classified according to the World Health Organization criteria. Serial immunohistologic stainings of human iliac arteries from 43 patients were performed using monoclonal antibodies. Lesions were classified according to World Health Organization criteria, and CD40 expression was analyzed with regard to cell morphology and cellular markers by 2 independent observers. Human atherosclerotic lesions revealed a significant increase in intimal thickness, number of inflammatory infiltrates, and CD40-positive macrophages and vascular smooth muscle cells with progression of the lesions. This increase was most prominent from stage 0 to stage I. A significant correlation between intimal thickness and CD40-positive macrophages (r = 0.75, p <0.0005) and CD40-positive vascular smooth muscle cells (r = 0.81, p <0.0005) was observed. Ligation of the cellular CD40 receptor contributes to inflammatory cellular events in human vascular smooth muscle cells. These data suggest a direct association of CD40 expression in atherosclerotic lesions with early plaque development.

Aged↗
PubMed2001

Comparison of magnetic resonance real-time imaging of left ventricular function with conventional magnetic resonance imaging and echocardiography.

This study analyzes the accuracy of a new real-time magnetic resonance imaging (MRI) technique (acquisition duration, 62 ms/image) and echocardiography for the determination of left ventricular (LV) end-diastolic volume, end-systolic volume, ejection fraction, and muscle mass when compared with turbo gradient echo imaging as the reference standard. Thirty-four patients were examined with digital echocardiography, standard, and real-time MRI. A close correlation was found between the results of real-time imaging and the reference standard for end-diastolic volume, end-systolic volume, and ejection fraction (r >0.95), with a lower correlation for LV muscle mass (r = 0.81). Correlations between echocardiography and the reference standard were lower for all parameters. Real-time MRI enables the acquisition of high-quality cine loops of the entire heart in minimal time without electrocardiographic triggering or breath holding. Thus, patient setup and scan time can be reduced considerably. Results are similar to the reference standard and superior to echocardiography for determining LV volumes and ejection fraction. This technique is a valid alternative to current approaches and can form the basis of every cardiac MRI examination.

Adult↗
PubMed2001

Multi-slice dynamic imaging: complete functional cardiac MR examination within 15 seconds.

A new magnetic resonance (MR) sequence was developed to acquire real-time images in a multi-slice dynamic imaging mode to cover the complete heart in 15 seconds without the need for electrocardiogram (ECG) triggering and multiple breath holds. In 34 patients, left ventricular function was assessed with the new technique and a standard technique. The new technique proved to be feasible and accurate for functional cardiac examinations.

Adult↗
PubMed2001

Magnetic resonance flow measurements in real time: comparison with a standard gradient-echo technique.

Ultrafast gradient systems and hybrid imaging sequences offer the opportunity to acquire phase contrast flow data in real time. In a 1.5-Tesla magnetic resonance (MR)-tomograph, peak velocity and volume flow were assessed in 36 large vessels (aorta) and 33 medium-sized vessels (carotid and iliac artery) using a real-time (segmented k-space turbo gradient-echo planar imaging sequence) in comparison with a gradient-echo technique. With the real-time technique, the matrix was reduced from 116 to 64, and temporal resolution changed from 30 msec to 124 msec. Measurements of peak velocity correlated in large (r = 0.88) and medium-sized vessels (r = 0.81). Volume flow measurements correlated in large vessels (r = 0.87), however, a poor correlation (r = 0.64) was found in medium-sized vessels. Thus, scan time can be significantly reduced and images acquired without electrocardiogram (ECG)-triggering. Flow volume can only be determined in large vessels with sufficient accuracy, mainly due to reduced spatial resolution in smaller vessels.

Blood Flow Velocity↗
PubMed2001

Functional cardiac MR imaging with steady-state free precession (SSFP) significantly improves endocardial border delineation without contrast agents.

Contrast between blood and myocardium in standard turbo gradient echo MR techniques (TFE) used routinely in clinical practice is mainly caused by unsaturated inflowing blood. Steady-state free precession (SSFP) has excellent contrast even in the absence of inflow effects. In 45 subjects cardiac cine loops in two long axis projections were acquired using TFE and compared with SSFP. A visual score (range 0 worst - 3 best) was assigned for endocardial border delineation for six myocardial segments in two long axis views. Endocardial border delineation score for TFE was 1.3 +/- 0.3 per segment and 2.4 +/- 0.3 for SSFP (P < 0.0001). Signal intensity blood/signal intensity myocardium was 1.5 +/- 0.4 at enddiastole and 1.4 +/- 0.3 at systole for TFE and 3.5 +/- 1.1 and 3.2 +/- 1.3 for SSFP, respectively (P < 0.0001). SSFP increases contrast between blood and myocardium more than twofold, resulting in an improved endocardial border definition. This may reduce variability for the determination of cardiac volumes and ejection fraction.

Adult↗
PubMed2001

Adenovirus-mediated overexpression and stimulation of the human angiotensin II type 2 receptor in porcine cardiac fibroblasts does not modulate proliferation, collagen I mRNA expression and ERK1/ERK2 activity, but inhibits protein tyrosine phosphatases.

The contribution of the angiotensin (Ang) II type 2 receptor (AT2R) to cardiac hypertrophy is still controversial. Here we examined the effect of overexpressing the human AT2R in cultured porcine cardiac fibroblasts (pFib) on proliferation, procollagen I mRNA expression, and - as putatively underlying signal-transduction pathways - on mitogen-activated protein kinase ERK1/ERK2 and phosphotyrosine phosphatase activities. As quantitated by 125I-(Sar1,Ile8)-Ang II binding, transduction of cardiac fibroblasts with the adenoviral AT2R expression vector led to a six- to tenfold higher AT2 than endogenous Ang II type 1 receptor (AT1R) expression. The overexpressed AT2R had the same apparent molecular mass as the endogenous AT2R in rat PC12W cells. Proliferation was not significantly lower in AT2R expressing pFib than in antisense-transduced controls (TA2) upon stimulation with Ang II (AT2R 110.5+/-4.8% vs. TA2 110.2+/-5.5%), Ang II plus the AT1R blocker Irbesartan (97.1+/-1.4% vs. 108.0+/-5.0; P=0.052) and the partial AT2R antagonist CGP42112 at the agonistic concentration of 50 nM (92.1+/-2.7% vs. 99.8+/-3.1%; P=0.053). Procollagen Ialpha2 (COL1A2) mRNA levels were quantitated by (a) northern blot analysis and (b) reverse transcriptase polymerase chain reaction. COL1A2/GAPDH (a) and COL1A2/beta-actin (b) ratios revealed no differences between AT2R-transduced fibroblasts and antisense controls when stimulated with Ang II (1 microM, 24 h) plus Irbesartan and 10 ng/ml transforming growth factor beta1. Ang II stimulation of the endogenous AT1R increased extracellular signal regulated kinase 1/2 activities. This response was reduced by Irbesartan, but PD123319 had no effect. Time course and magnitude of Ang II stimulated ERK1/ERK2 activation was identical in AT2R-transduced and control cells. Also, neither simultaneous nor Ang II pre-stimulation, suggested to induce gene expression of the MAP kinase phosphatase 1, modulated phorbol myristate acetate-stimulated ERK1/ERK2 activation in AT2R-transduced pFib, in AT2R-transduced human umbilical vein endothelial cells, and in PC12W cells. By the use of a tyrosine phosphatase assay we observed an inhibition of phosphotyrosine phosphatase activity by 30.8% (P=0.009, n=5) after 5 min Ang II stimulation of AT2R-expressing pFib. Immunoprecipitation-tyrosine phosphatase assays revealed that inhibition of phosphotyrosine phosphatase 1B, which regulates insulin signaling, contributed to this effect. In conclusion, stimulation of the overexpressed human AT2R in porcine cardiac fibroblasts inhibited tyrosine phosphatase activity but had no significant effect on fibroblast functions related to cardiac fibrosis. It is conceivable that possible antifibrotic AT2R effects are species specific and/or require the interaction between fibroblasts and cardiomyocytes, probably via paracrine factors, or mechanical load.

Adenoviridae↗
PubMed2001

[Comparison of various parameters for determining an index of myocardial perfusion reserve in detecting coronary stenosis with cardiovascular magnetic resonance tomography].

For the assessment of myocardial perfusion with cardiac magnetic resonance imaging, different semiquantitative parameters of the first pass signal intensity time curves can be calculated and myocardial perfusion reserve indices can be determined. In this study we evaluated the feasibility of different perfusion parameters and their perfusion reserve indices for the detection of significant coronary artery stenosis. The signal intensity time curves of the first pass of a gadolinium-DTPA bolus injected via a central vein catheter before and after dipyridamole infusion were investigated in 15 patients with single vessel (stenosis > or = 75% area reduction) and five patients without significant coronary artery disease. For the distinction of ischemic and nonischemic myocardial segments, semiquantitative parameters, such as maximal signal intensity, contrast appearance time, time to maximal signal intensity and the steepness of the signal intensity curve's upslope determined by a linear fit, were assessed after correction for the input function. For each parameter a myocardial perfusion reserve index was calculated and cut off values for the detection of significant coronary stenosis were defined. The diagnostic accuracy of each parameter was then examined prospectively in 36 patients with coronary artery disease and compared with coronary angiography. Where as a distinction of ischemic and normal myocardium was possible with myocardial perfusion reserve indices, semiquantitative parameters at rest or after vasodilation alone did not allow such a distinction. The perfusion reserve index calculated from the upslope showed the most significant difference between ischemic and nonischemic myocardial segments (1.19 +/- 0.4 and 2.38 +/- 0.45, p < 0.001) followed by maximum signal intensity, time to maximum signal intensity and contrast apperance time. Sensitivity, specificity and diagnostic accuracy was 87, 82 and 85% for the detection of hypoperfusion induced by significant coronary artery stenoses using the perfusion reserve index calculated from the upslope. The steepness of the first pass signal intensity curve's upslope, determined by a linear fit, is a feasible parameter for the detection of significant coronary artery disease with MR. Based on a myocardial perfusion reserve index of this parameter, ischemic myocardium can be identified with high diagnostic accuracy.

Adult↗
PubMed2001

Integrins alphavbeta3 and alphavbeta5 mediate VSMC migration and are elevated during neointima formation in the rat aorta.

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of alphavbeta3, but not alphavbeta5 integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of alphavbeta3 and alphavbeta5 integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying neointima formation in vivo. RASMC and HCSMC express alphavbeta3 and alphavbeta5 integrin subunits. The alphavbeta5 integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the alphavbeta3 integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through gelatin coated membranes involved both alphavbeta3 and alphavbeta5 integrins. Selective blocking antibodies for alphavbeta3 and alphavbeta5 inhibited migration of RASMC and HCSMC by more than 60 % (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for alphav, beta3 and beta5 mRNA in uninjured aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of alphav, beta3 and beta5 mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased integrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that alphavbeta3 and alphavbeta5 are elevated during neointima formation in the rat and indicates a novel role for alphavbeta5 participating in mechanisms regulating smooth muscle cell migration.

Animals↗
PubMed2001

TNFalpha induces expression of transcription factors c-fos, Egr-1, and Ets-1 in vascular lesions through extracellular signal-regulated kinases 1/2.

Migration, proliferation and differentiation of vascular smooth muscle cells (VSMC) and macrophages are important pathological responses that contribute to the development and progression of vascular lesions. Cytokines such as TNFalpha are present at sites of vascular injury and regulate a variety of cellular functions of inflammatory cells and VSMC. Cell migration, proliferation and differentiation require de novo gene transcription resulting from extracellular signals being transduced to the nucleus, where multiple genes are regulated to participate in lesion formation. In VSMC and macrophages, TNFalpha induces activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2), which transmit signals from the cytosol to the nucleus. Potential nuclear targets of TNFalpha-activated ERK 1/2 include the transcription factors Ets-1, Egr-1, and c-fos, which are known to regulate cellular growth, differentiation, and migration. The aim of this study was to investigate the expression of the transcription factors Ets-1, Egr-1 and c-fos in different types of vascular lesions, their regulation by TNFalpha and the role of ERK 1/2 in these signaling events. Atherosclerotic lesions from fructose-fed LDL-receptor deficient mice and neointimal lesions from rat aortae 2 weeks post balloon injury demonstrated the presence and colocalization of TNFalpha, phosphorylated and activated ERK 1/2, and transcription factors Ets-1, Egr-1 and c-fos. Neointimal lesions consisted primarily of VSMC, whereas atherosclerotic lesions predominantly contained macrophages. In cultured rat aortic VSMC, TNFalpha (100 U/ml) stimulated a rapid and transient expression of Ets-1, Egr-1 and c-fos with a maximal induction 1 h after stimulation. In cultured RAW 264.7 mouse macrophages, TNFalpha similarly induced the expression of Ets-1, Egr-1, and c-fos. Induction of these transcription factors was mediated via ERK 1/2 activation, since the ERK 1/2-pathway inhibitor PD98059 (10-30 microM) significantly inhibited their TNFalpha-induced expression. TNFalpha induced ERK 1/2 activation in both cell types. These findings underscore the importance of the ERK 1/2 pathway in the expression of TNFalpha-regulated transcription factors, which may participate in different forms of vascular lesion formation.

Animals↗
PubMed2001

Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans.

OBJECTIVES: Our study goal was to analyze whether gene variants of angiotensin II type 2-receptor (AT2-R) modulate the effects of angiotensin II on the left ventricle (LV). BACKGROUND: Experimental data suggest that angiotensin II modifies ventricular growth responses via angiotensin II type 1-receptors (AT1-R) and AT2-R. METHODS: In 120 white, young male subjects with normal or mildly elevated blood pressure, we assessed plasma angiotensin II and aldosterone concentrations (RIA), 24-h urinary sodium excretion, 24-h ambulatory blood pressure and LV structure (two-dimensional guided M-mode echocardiography). The intronic +1675 G/A polymorphism of the X-chromosomal located AT2-R gene was investigated by single-strand conformational polymorphism analysis and DNA-sequencing. RESULTS: Hypertensive subjects with the A-allele had a greater LV posterior (11.0 +/- 1.3 vs. 9.9 +/- 1.3 mm, p < 0.001), septal (11.8 +/- 1.4 vs. 10.1 +/- 1.2 mm, p < 0.001) and relative wall thickness (0.44 +/- 0.06 vs. 0.39 +/- 0.06, p < 0.01) as well as LV mass index (138 +/- 23 vs. 120 +/- 13 g/m2, p < 0.001) than those with the G-allele. Confounding factors (i.e., body mass index and surface area, plasma angiotensin II, sodium excretion, systolic and diastolic ambulatory blood pressure) were similar between the two genotypes. In normotensive subjects, relative wall thickness (0.36 +/- 0.05 vs. 0.35 +/- 0.05) and LV mass index (115 +/- 21 vs. 112 +/- 17 g/m2) were nearly identical across the two genotypes, with similar confounding variables. CONCLUSIONS: Our data indicate that the X-chromosomal located +1675 G/A-polymorphism of the AT2-R gene is associated with LV structure in young male humans with early structural changes of the heart due to arterial hypertension.

Adult↗