Decreased Nox4 levels in the myocardium of patients with aortic valve stenosis

2013 ◽  
Vol 125 (6) ◽  
pp. 291-300 ◽  
Author(s):  
María U. Moreno ◽  
Idoia Gallego ◽  
Begoña López ◽  
Arantxa González ◽  
Ana Fortuño ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Animal Studies ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cross Sectional ◽  
Replacement Surgery ◽  
Myocardial Remodelling ◽  
And Function

The NADPH oxidases are a key family of ROS (reactive oxygen species)-producing enzymes which may differentially contribute to cardiac pathophysiology. Animal studies show uncertain results regarding the regulation of cardiac Nox4 by pressure overload and no data are available on human myocardial Nox4. In the present study, we evaluated Nox4 expression and its relationship with myocardial remodelling and LV (left ventricular) function in patients with severe AS (aortic valve stenosis). Endomyocardial biopsies from 34 patients with AS were obtained during aortic valve replacement surgery. LV morphology and function were assessed by echocardiography. Myocardial samples from subjects deceased of non-CVDs (cardiovascular diseases) were analysed as controls. Nox4 localization was evaluated by immunohistochemistry and quantified by Western blot. Myocardial capillary density, fibrosis and cardiomyocyte dimensions and apoptosis were assessed histologically to evaluate myocardial remodelling. Nox4 was present in samples from all subjects and expressed in cardiomyocytes, VSMCs (vascular smooth muscle cells), endothelium and fibroblasts. Nox4 levels were reduced 5-fold in AS patients compared with controls (P<0.01). Nox4 levels directly correlated with cardiomyocyte cross-sectional area (r=0.299, P<0.05) and diameter (r=0.406, P<0.05) and capillary density (r=0.389, P<0.05), and inversely with cardiomyocyte apoptosis (r=−0.316, P<0.05) in AS patients. In addition, Nox4 levels correlated with echocardiographic parameters (LV ejection fraction: r=0.353, P<0.05; midwall fractional shortening: r=0.355, P<0.05; deceleration time: r=−0.345, P<0.05) in AS patients. Nox4 is expressed in human myocardium and reduced in AS patients. The observed associations of Nox4 with cardiomyocyte parameters and capillary density in AS patients suggest a potential role of Nox4 deficiency in the myocardial remodelling present in the human pressure-overloaded heart.

Cardiac vasculature and flow during pressure-overload hypertrophy

1986 ◽  
Vol 251 (5) ◽  
pp. H1031-H1037 ◽  
Author(s):  
E. A. Breisch ◽  
F. C. White ◽  
L. E. Nimmo ◽  
C. M. Bloor
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Control Group ◽  
Cross Sectional ◽  
Ventricle Hypertrophy ◽  
Aortic Cuff

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

Aortic valve stenosis

2015 ◽  
pp. 129-140
Author(s):  
Helmut Baumgartner ◽  
Erwan Donal ◽  
Stefan Orwat ◽  
Axel Schmermund ◽  
Raphael Rosenhek ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Continuity Equation ◽  
Imaging Techniques ◽  
Integrated Approach ◽  
Aortic Disease ◽  
Left Ventricular ◽  
Prognostic Information ◽  
And Function ◽  
Available Information

Echocardiography is the method of choice for the diagnosis, assessment of morphology, and aetiology, as well as quantification of aortic valve stenosis. It permits the additional evaluation of the consequences on left ventricular size and, function, wall thickness, mitral valve (functional regurgitation).Haemodynamic assessment can be performed by Doppler echocardiography providing transvalvular gradients and valve areas can be determined by the continuity equation. Recently, MR and CT imaging have gained importance for assessment of valve morphology, ventricular function, and associated aortic disease. In current practice their role in quantifying severity of valve stenosis, however, remains limited. It is important to be aware of the specific limitations and pitfalls of the various measurements. Final judgement should be based on an integrated approach involving all available information. Finally, imaging techniques provide important prognostic information in aortic valve stenosis and have a fundamental impact on the decision making process in clinical practice.

scholarly journals Management of patients with combined arterial hypertension and aortic valve stenosis: a consensus document from the Council on Hypertension and Council on Valvular Heart Disease of the European Society of Cardiology, the European Association of Cardiovascular Imaging (EACVI), and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

2020 ◽  
Author(s):  
Costantino Mancusi ◽  
Giovanni de Simone ◽  
Jana Brguljan Hitij ◽  
Isabella Sudano ◽  
Felix Mahfoud ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Arterial Hypertension ◽  
Aortic Valve Stenosis ◽  
European Association ◽  
Antihypertensive Drugs ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Expert Advice ◽  
Current Evidence ◽  
Drug Induced

Abstract Aortic valve stenosis (AS) is the third most common cardiovascular disease. The prevalence of both AS and arterial hypertension increases with age, and the conditions therefore often co-exist. Co-existence of AS and arterial hypertension is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Arterial hypertension may also influence grading of AS, leading to underestimation of the true AS severity. Current guidelines suggest re-assessing patients once arterial hypertension is controlled. Management of arterial hypertension in AS has historically been associated with prudence and concerns, mainly related to potential adverse consequences of drug-induced peripheral vasodilatation combined with reduced stroke volume due to the fixed LV outflow obstruction. Current evidence suggests that patients should be treated with antihypertensive drugs blocking the renin–angiotensin–aldosterone system, adding further drug classes when required, to achieve similar target blood pressure (BP) values as in hypertensive patients without AS. The introduction of transcatheter aortic valve implantation has revolutionized the management of patients with AS, but requires proper BP management during and following valve replacement. The purpose of this document is to review the recent evidence and provide practical expert advice on management of hypertension in patients with AS.

Sympathectomy stimulates capillary but not precapillary growth in hypertrophic hearts

1991 ◽  
Vol 260 (5) ◽  
pp. H1515-H1521
Author(s):  
R. J. Torry ◽  
P. M. Connell ◽  
D. M. O'Brien ◽  
W. M. Chilian ◽  
R. J. Tomanek
Keyword(s):  
Pressure Overload ◽  
Sympathetic Nerves ◽  
Capillary Density ◽  
Volume Density ◽  
Left Ventricular ◽  
Coronary Vasodilation ◽  
Cross Sectional ◽  
Vascular Growth ◽  
Capillary Growth ◽  
Intercapillary Distance

Sympathetic nerves are known to influence vascular growth, but their role in coronary vascular adaptations to pressure-overload left ventricular (LV) hypertrophy is unknown. Accordingly, regional sympathectomy (SYMX) was produced by painting a ring of phenol on the posterior third of the LV in seven renal hypertensive (Page: 1 kidney, 1 wrap) and seven normotensive (sham: 1 kidney, no wrap) rabbits. Two months later, maximal myocardial blood flow (MBF) following dipyridamole-induced coronary vasodilation was determined with microspheres in the intact anterior and the sympathectomized posterior regions of conscious rabbits. Histomorphometric methods were then utilized to evaluate capillary density (CD), intercapillary distance (ICD), and volume density (VD) of subepicardial and endocardial samples of each region of perfused-fixed hearts. The Page procedure significantly increased systolic blood pressure (+29%) and LV wt/body wt (+20%) above sham rabbits. In both sham and Page groups, MBF was not significantly different between intact and sympathectomized regions within either group. SYMX did not significantly alter CD, ICD, or VD between regions in the sham animals. In contrast, SYMX significantly increased CD (+30%) and VD (+26%) and decreased ICD (-21%) in the subendocardial region of Page animals. Regional SYMX did not alter myocyte cross-sectional area in Page animals. We conclude that SYMX neither 1) significantly increases resistance vessel cross-sectional lumen area in either normal or hypertrophic hearts, nor 2) significantly influences capillary growth in normal hearts, but SYMX does 3) promote capillary growth in hearts undergoing hypertrophy in response to hypertension.

scholarly journals NADPH oxidase-4 promotes eccentric cardiac hypertrophy in response to volume overload

2019 ◽  
Author(s):  
Moritz Schnelle ◽  
Iain Sawyer ◽  
Narayana Anilkumar ◽  
Belal A Mohamed ◽  
Daniel A Richards ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Cardiac Hypertrophy ◽  
Interstitial Fibrosis ◽  
Pressure Overload ◽  
Volume Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Cross Sectional ◽  
Nadph Oxidase 4

Abstract Aims Chronic pressure or volume overload induce concentric vs. eccentric left ventricular (LV) remodelling, respectively. Previous studies suggest that distinct signalling pathways are involved in these responses. NADPH oxidase-4 (Nox4) is a reactive oxygen species-generating enzyme that can limit detrimental cardiac remodelling in response to pressure overload. This study aimed to assess its role in volume overload-induced remodelling. Methods and results We compared the responses to creation of an aortocaval fistula (Shunt) to induce volume overload in Nox4-null mice (Nox4−/−) vs. wild-type (WT) littermates. Induction of Shunt resulted in a significant increase in cardiac Nox4 mRNA and protein levels in WT mice as compared to Sham controls. Nox4−/− mice developed less eccentric LV remodelling than WT mice (echocardiographic relative wall thickness: 0.30 vs. 0.27, P &lt; 0.05), with less LV hypertrophy at organ level (increase in LV weight/tibia length ratio of 25% vs. 43%, P &lt; 0.01) and cellular level (cardiomyocyte cross-sectional area: 323 µm2 vs. 379 μm2, P &lt; 0.01). LV ejection fraction, foetal gene expression, interstitial fibrosis, myocardial capillary density, and levels of myocyte apoptosis after Shunt were similar in the two genotypes. Myocardial phospho-Akt levels were increased after induction of Shunt in WT mice, whereas levels decreased in Nox4−/− mice (+29% vs. −21%, P &lt; 0.05), associated with a higher level of phosphorylation of the S6 ribosomal protein (S6) and the eIF4E-binding protein 1 (4E-BP1) in WT compared to Nox4−/− mice. We identified that Akt activation in cardiac cells is augmented by Nox4 via a Src kinase-dependent inactivation of protein phosphatase 2A. Conclusion Endogenous Nox4 is required for the full development of eccentric cardiac hypertrophy and remodelling during chronic volume overload. Nox4-dependent activation of Akt and its downstream targets S6 and 4E-BP1 may be involved in this effect.

Left Ventricular Remodeling in Degenerative Aortic Valve Stenosis

2021 ◽  
Vol 46 (5) ◽  
pp. 100801
Author(s):  
João Abecasis ◽  
Daniel Gomes Pinto ◽  
Sância Ramos ◽  
Pier Giorgio Masci ◽  
Nuno Cardim ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular
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