P3507Heterozygous cardiomyocyte-specific deletion of ErbB4 sensitizes to development of pregnancy-related cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Feyen ◽  
Z Vermeulen ◽  
L Dugaucquier ◽  
D Hilfiker-Kleiner ◽  
V F M Segers ◽  
...  
Keyword(s):  
Systolic Dysfunction ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Macrophage Infiltration ◽  
Cardiomyocyte Hypertrophy ◽  
Sectional Area ◽  
Wild Type ◽  
Cross Sectional ◽  
Specific Deletion

Abstract Background Peripartum cardiomyopathy (PPCM) is a potentially life-threatening disease in women without known cardiovascular disease; PPCM is characterized by left ventricular (LV) systolic dysfunction towards the end of pregnancy and/or in the first months postpartum. The underlying mechanisms of PPCM are incompletely understood, but there is recent evidence that impaired cardiomyocyte expression of the tyrosine kinase ErbB4 receptor plays a role. ErbB4 is the main receptor of neuregulin-1, a protective and regenerative paracrine factor in the heart. Homozygous deletion of ErbB4 is lethal. Purpose To test the hypothesis that mice with heterozygous (HZ) cardiomyocyte-specific deletion of ErbB4 (ErbB4+/−) are more susceptible to PPCM. Methods Cardiac morphology and function was evaluated by echocardiography with a Vevo 2100 Imaging System during 2 pregnancies and 6 weeks postpartum (n=7–9) or during non-pregnant control conditions in HZ (ErbB4+/−) and wild type controls (n=9–10). Then, hearts were excised for analyses of myocardial fibrosis, macrophage infiltration, capillary density and cardiomyocyte cross sectional area. Results When compared to pregnant wild type controls, pregnant ErbB4+/− mice developed significant LV dilatation (2 weeks after the 2nd delivery: LVIDd +16% ± 2%, p<0.05) and dysfunction (6 weeks after the 2nd delivery: EF −23% ± 3%, p<0.001), increased heart to body weight ratio (+7% ± 4%, p<0.05) and increased cardiomyocyte cross sectional area (+28% ± 7%, p<0.01). Non-pregnant ErbB4+/− mice also developed LV dilatation and dysfunction, albeit slower than pregnant ErbB4+/− mice. On histology, however, myocardial tissue of pregnant ErbB4+/− mice did not show macrophage infiltration, neither fibrosis, nor reduced capillary density. Conclusions Heterozygous cardiomyocyte-specific deletion of ErbB4 sensitizes to peripartum LV dilatation and cardiomyocyte hypertrophy and systolic dysfunction without profound cardiac injury, features that are frequently present in PPCM patients and may explain their high chance for recovery. These data reinforce a compensatory role for neuregulin-ErbB4 signaling during hemodynamic overload, and confirm that this signaling pathway is important to protect the maternal heart during peripartum stress. Acknowledgement/Funding Fund scientific research Flanders; University Antwerp

scholarly journals Cardiomyocyte remodeling in ischemic heart disease

Medicina ◽  
2008 ◽  
Vol 44 (11) ◽  
pp. 848 ◽  
Author(s):  
Dalia Pangonytė ◽  
Elena Stalioraitytė ◽  
Reda Žiuraitienė ◽  
Danutė Kazlauskaitė ◽  
Jolita Palubinskienė ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Ischemic Heart ◽  
Cardiomyocyte Hypertrophy ◽  
Control Group ◽  
Sectional Area ◽  
Cross Sectional

Objective. The aim of the study was to detect changes in left ventricular cardiomyocyte size and shape in response to chronic ischemia and loss of cardiac tissue (myocardial infarction) during the course of ischemic heart disease (IHD). Material and methods. Left ventricular cardiomyocyte dimensions (diameter and length) were estimated histomorphometrically, and their cross-sectional area and volume were assessed in 85 males who died suddenly out of hospital (within 6 hours of the onset of the terminal event) due to the acute first (preinfarction IHD group, n=53, aged 48.6±2.9 years) or repeated (postinfarction IHD group, n=32, aged 51.7±2.9 years) IHD attack, and had no other causes for the increased heart load. Twenty-nine males of similar age (mean age, 46.0±3.1 years) who succumbed to external causes served as controls. Results. We have found cardiomyocyte hypertrophy in the preinfarction IHD group already. The cardiomyocyte volume was increased by 32.0% in comparison with the same index in the control group, and cross-sectional area and length – by 17.2 and 12.5%, respectively. In postinfarction IHD group, all studied cardiomyocyte parameters did not differ significantly from the analogous indices in the preinfarction IHD group (P>0.05). Cardiomyocyte hypertrophy was related to the increase in left ventricular cardiomyocyte parameters. Conclusions. Left ventricular cardiomyocyte hypertrophy occurs before the first myocardial infarction. In postinfarction myocardium, cardiomyocyte dimensions do not differ significantly at least prior to the appearance of congestive heart failure syndrome.

Abstract 79: Autophagy Is Necessary in Reversal of Left Ventricular Hypertrophy

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Jota Oyabu ◽  
Osamu Yamaguchi ◽  
Kinya Otsu
Keyword(s):  
Body Weight ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Cardiomyocyte Hypertrophy ◽  
Sectional Area ◽  
Cross Sectional ◽  
Lv Mass ◽  
Continuous Injection

Myocardial hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Left ventricular hypertrophy (LVH) in the long term is an independent risk factor for a range of adverse consequences, such as cardiac dysfunction and cardiac mortality. Therefore, prevention or regression of LVH can be a major therapeutic target. Although reversal of LVH occurs after control of etiological factors, the molecular mechanisms remain to be clarified. We have previously reported that inhibition of autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, induces cardiomyocyte hypertrophy. In the present study, we investigated the role of autophagy in the course of reversal of LVH. Wild-type mice showed left ventricular hypertrophy by continuous injection of angiotensin II (A-II) for 14 days using osmotic mini-pump, and LVH was reversed 7 days after removal of pump. Autophagy was induced after removal of pump, as evidenced by an increase in LC3-II protein levels. Next, we crossed floxed Atg5 mice with transgenic mice expressing Cre recombinase in cardiac specific manner to generate cardiac-specific autophagy-deficient mice (CKO). We subjected CKO and control mice (CTL) to continuous injection of A-II for 14 days. CKO and CTL showed LVH similarly (LV weight/body weight, CKO 4.60±0.16 versus CTL 4.44±0.08, p=n.s., LV mass index, CKO 69.0±5.5 versus CTL 72.1±2.2, p=n.s.) without showing contractile dysfunction 14 days after injection of A-II. Cross-sectional area of cardiomyocytes was similar in CKO and CTL (CKO 281.0±1.0 μm 2 versus CTL 274.0±1.5 μm 2 , p=n.s.). 7days after removal of pump, CKO showed significantly less reversal of LVH compared with CTL (LV weight/body weight, CKO 4.30±0.13 versus CTL 3.65±0.09, p<0.05, LV mass index, CKO 67.8±3.8 versus CTL 56.2±2.6, p<0.05). Cross-sectional area of cardiomyocytes also showed less reversal of LVH in CKO (CKO 270.6.0±7.0 μm 2 versus CTL 220.9±11.4 μm 2 , p<0.05), indicating that reversal of LVH didn’t occur sufficiently in autophagy-deficient heart. Autophagy was suppressed during reversal of LVH in CKO. These results suggest that autophagy is necessary in reversal of LVH.

Relation between Coronary Artery Cross Sectional Area and Left Ventricular Wall Mass

1990 ◽  
Vol 20 (4) ◽  
pp. 748
Author(s):  
Doo Hong Choi ◽  
Hak Sun Kim ◽  
Sun Ho Chang ◽  
Joo Young Cho ◽  
Sung Gu Kim ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Left Ventricular Wall ◽  
Ventricular Wall ◽  
Sectional Area ◽  
Cross Sectional ◽  
Wall Mass

Role of superoxide anion in regulating pressor and vascular hypertrophic response to angiotensin II

2002 ◽  
Vol 282 (5) ◽  
pp. H1697-H1702 ◽  
Author(s):  
Hui Di Wang ◽  
Douglas G. Johns ◽  
Shanqin Xu ◽  
Richard A. Cohen
Keyword(s):  
Superoxide Anion ◽  
Pressor Response ◽  
Cross Sectional Area ◽  
Ang Ii ◽  
Sectional Area ◽  
Wild Type ◽  
Cross Sectional ◽  
Hypertrophic Response

Our purpose was to address the role of NAPDH oxidase-derived superoxide anion in the vascular response to ANG II. Blood pressure, aortic superoxide anion, 3-nitrotyrosine, and medial cross-sectional area were compared in wild-type mice and in mice that overexpress human superoxide dismutase (hSOD). The pressor response to ANG II was significantly less in hSOD mice. Superoxide anion levels were increased twofold in ANG II-treated wild-type mice but not in hSOD mice. 3-Nitrotyrosine increased in aortic endothelium and adventitia in wild-type but not hSOD mice. In contrast, aortic medial cross-sectional area increased 50% with ANG II in hSOD mice, comparable to wild-type mice. The lower pressor response to ANG II in the mice expressing hSOD is consistent with a pressor role of superoxide anion in wild-type mice, most likely because it reacts with nitric oxide. Despite preventing the increase in superoxide anion and 3-nitrotyrosine, the aortic hypertrophic response to ANG II in vivo was unaffected by hSOD.

Left ventricular wave speed

2001 ◽  
Vol 91 (6) ◽  
pp. 2531-2536 ◽  
Author(s):  
Jiun-Jr Wang ◽  
Kim H. Parker ◽  
John V. Tyberg
Keyword(s):  
Wave Speed ◽  
Pulse Generator ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Pressure Transducers ◽  
Pressure Area ◽  
Axis Length

Left ventricular (LV) wave speed (LVWS) was studied experimentally and confirmed in theory. Combining the definition of elastance (E) with the equations for the conservation of mass and momentum shows that LVWS is proportional to the square root of E LA, where L is long-axis length and A is the cross-sectional area, and the density of the blood. (We defined E LA = γ, where γ is compressibility.) We studied nine open chest, anesthetized dogs, three of which were studied during caval constriction when LV end-diastolic pressure was ≤0 mmHg. The hearts were paced at ∼90 beats/min, and LV cross-sectional area was measured by using two pairs of ultrasonic crystals; E was calculated from the LV pressure-area loop. A pulse generator was connected to the LV apex, and LVWS was measured by using two pressure transducers: one near the apex and the other near the base. Their distance was measured roentgenographically and compared with the diameter of a reference ball. LVWS ranged from ∼1 m/s during diastole to ∼10 m/s during systole. The slope of the log c(where c is wave speed) vs. log γ was 0.546, which is in agreement with theory (0.5). When γ ≤ 0, LVWS was ∼1.5 m/s.

Influences of physical conditioning and deconditioning on coronary vasculature of dogs

1978 ◽  
Vol 45 (4) ◽  
pp. 619-625 ◽  
Author(s):  
H. L. Wyatt ◽  
J. Mitchell
Keyword(s):  
Basement Membrane ◽  
Capillary Density ◽  
Cross Sectional Area ◽  
Membrane Thickness ◽  
Physical Conditioning ◽  
Sectional Area ◽  
Circumflex Artery ◽  
Cross Sectional ◽  
Coronary Vasculature ◽  
Basement Membrane Thickness

To investigate the effects of physical conditioning and deconditioning on the coronary vasculature, eight dogs were exercised by treadmill running. Five dogs were deconditioned by confinement in cages following the conditioning period. A technique was developed and validated for measuring circumflex coronary artery diameter from magnified projections of standardized coronary angiograms. Myocardial capillary density, perimeter, and basement membrane thickness were determined from electron microscopy of serial ventricular septal biopsy samples. Physical conditioning caused a small but statistically significant increase in cross-sectional area of the circumflex artery. Although physical conditioning caused no statistically significant changes in the myocardial capillaries, trends were apparent for increases in density and perimeter of myocardial capillaries and a decrease in basement membrane thickness. Physical deconditioning caused statistically significant reductions in cross-sectional area of the circumflex artery and in myocardial capillary density but little change in perimeter or basement membrane thickness of myocardial capillaries. The results suggest that physical conditioning may be associated with an improvement in coronary vascular capacity which may regress rapidly with deconditioning.

Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes

Heart ◽  
2020 ◽  
Vol 106 (15) ◽  
pp. 1176-1182
Author(s):  
Timothy C Tan ◽  
Maria Carmo Pereira Nunes ◽  
Mark Handschumacher ◽  
Octavio Pontes-Neto ◽  
Yong-Hyun Park ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Flow Velocity ◽  
Left Atrial ◽  
Velocity Profiles ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Left Ventricular Ejection ◽  
Sectional Area ◽  
Cross Sectional

ObjectiveCardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes.MethodsA cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA.ResultsA total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119).ConclusionsLA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

P5457Assessment of carotid cross sectional area in hypertensive patients: phenotyping and prognostic validation in the campania salute network

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Mancusi ◽  
R Izzo ◽  
M A Losi ◽  
E Barbato ◽  
V Trimarco ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Cross Sectional Area ◽  
Older Age ◽  
Prognostic Impact ◽  
Sectional Area ◽  
Cross Sectional ◽  
Hypertensive Patients ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Male Sex

Abstract Background Increased intima media thickness (IMT) of common carotid artery (CA) is considered the hallmark of vascular hypertension-mediated target organ damage, even though vessel remodeling due to mechanical stress can be accompanied also by changes in diameter. Purpose We developed a method computing both diameter and IMT of CA, and assessed correlates and prognostic impact of carotid cross sectional area (CCSA) in a large registry of treated hypertensive patients. Methods We selected 7049 hypertensive patients of the Campania Salute Network registry free of overt cardiovascular (CV) disease and with available CA ultrasound (54±11 yrs; 57% male). CCSA was computed as: π × [((CA diameter + 2 × (mean IMT)) / 2)]2 − π × [((CA diameter) / 2)]2. Results CCSA was considered high if >90th percentile of the sex-specific distribution (>48 mm2 in men and >41 mm2 in women). Higher CCSA correlated with older age, male sex, higher pulse pressure (PP), higher total and LDL cholesterol and presence of diabetes (p<0.01 for all). During a median follow-up of 45 months (IQR 19–92), 324 incident composite major and minor CV events occurred. In Cox regression analysis high CCSA was associated with more than 100% increased risk of incident CV events (p<0.0001, figure), independently of the effect of older age, male sex, PP>60mmHg, presence of left ventricular hypertrophy (LVH), carotid plaque (CP), and less anti-RAS therapy (p<0.05 for all). Conclusions In treated hypertensive patients, increased CCSA is associated with worse metabolic and lipid profile and predict incident CV events, independently of high PP, presence of LVH and CP.

Long-term isoprenaline administration produces an increase in capillarity in the soleus muscle of the rat

1987 ◽  
Vol 65 (3) ◽  
pp. 303-306 ◽  
Author(s):  
A. H. Sillau ◽  
Maria De Lourdes Philippi
Keyword(s):  
Soleus Muscle ◽  
Cross Sections ◽  
Citrate Synthase ◽  
Lactic Dehydrogenase ◽  
Capillary Density ◽  
Oxidative Capacity ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Adrenergic Stimulation ◽  
Cross Sectional

The effects of isoprenaline administration (300 μg/kg for 5 weeks) on rat soleus muscle capillarity and glycolytic and oxidative capacities were evaluated. The treatment resulted in ventricular hypertrophy. The activities of lactic dehydrogenase, pyruvate kinase, citrate synthase, and cytochrome c oxidase in soleus muscle homogenates were not different between control and isoprenaline-injected animals. Capillaries were visualized in muscle cross sections treated to demonstrate ATPase activity after acid preincubation. Capillary density was higher in the experimental (873 ± 38 capillaries/mm2) than in the control (713 ± 33 capillaries/mm2) animals. Capillary to fiber ratio was also higher in the experimental (2.47 ± 0.10) than in control (2.09 ± 0.08) animals, but fiber cross-sectional area was not changed by the treatment (2836 ± 87 μm2 in controls and 2951 ± 136 μm2 in experimental). A plot of capillary to fiber ratio vs. fiber cross-sectional area showed that at a given fiber cross-sectional area the value of capillary to fiber ratio of the treated animals was higher than that of the controls. This indicates that treatment resulted in the proliferation of microvessels. The results suggest that prolonged β-adrenergic stimulation results in the development of new capillaries but that this is not accompanied by increases in the oxidative capacity of the soleus muscle of the rat.

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