scholarly journals Sexual Dimorphism in Testosterone Programming of Cardiomyocyte Development in Sheep

2021 ◽  
Author(s):  
Adel Ghnenis ◽  
Vasantha Padmanabhan ◽  
Arpita Vyas
Keyword(s):  
Natriuretic Peptide ◽  
Mammalian Target Of Rapamycin ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Phosphatidylinositol 3 Kinase ◽  
Compensatory Response ◽  
Lv Dysfunction ◽  
Cardiomyocyte Number ◽  
Group Sex ◽  
Female Specific

Abstract Perturbed in-utero hormone milieu leads to intrauterine growth retardation (IUGR), a known risk factor for left ventricular (LV) dysfunction later in life. Gestational testosterone (T) excess predisposes offspring to IUGR and leads to LV myocardial disarray and hypertension in adult females. However, the early impact of T excess on LV programming and if it is female-specific is unknown. LV tissues were obtained at day 90 gestation from days 30-90 T-treated or control fetuses (n=6/group/sex) and morphometric and molecular analyses were conducted. Gestational T treatment increased cardiomyocyte number only in female fetuses. T excess up-regulated receptor expression of insulin and insulin-like growth factor. Furthermore, in a sex-specific manner, T increased expression of Phosphatidylinositol 3-kinase (PI3K) while down regulating phosphorylated mammalian target of rapamycin (pmTOR) /mTOR ratio suggestive of compensatory response. T excess 1) upregulated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), markers of stress and cardiac hypertrophy 2) upregulated estrogen receptors1 (ESR1) and 2 (ESR2) but not in androgen receptor (AR). Thus, gestational T excess upregulated markers of cardiac stress and hypertrophy in both sexes while inducing cardiomyocyte hyperplasia only in females, likely mediated via insulin and estrogenic programming.

Association between Serum N-Terminal Pro-Brain Natriuretic Peptide Concentration and Left Ventricular Dysfunction and Extracellular Water in Continuous Ambulatory Peritoneal Dialysis Patients

2006 ◽  
Vol 26 (3) ◽  
pp. 360-365 ◽  
Author(s):  
Jung-Ahn Lee ◽  
Do-Hyoung Kim ◽  
Soo-Jeong Yoo ◽  
Dong-Jin Oh ◽  
Suk-Hee Yu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Left Ventricular ◽  
Extracellular Water ◽  
Volume Load ◽  
Lv Dysfunction ◽  
Lv Ejection Fraction

Background This study investigated the association between serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and extracellular water (ECW%) and left ventricular (LV) dysfunction in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods The study involved 30 stable CAPD patients: 14 males, 16 females; mean age 52 ± 14 years; mean CAPD duration 34 ± 12 months; 12 with diabetes mellitus (DM) and 18 non-DM. Serum NT-pro-BNP levels were determined using electrochemiluminescence immunoassay. Baseline echocardiography was performed using a Hewlett-Packard Sonos 1000 (Andover, Massachusetts, USA) device equipped with a 2.25-MHz probe, allowing M-mode, two-dimensional, and pulsed Doppler measurements. Left ventricular mass index (LVMI) was calculated according to the Penn formula. A multifrequency bioimpedance analyzer was used; ECW% was calculated as a percentage of total body water and was considered the index of volume load. Results ( 1 ) Serum NT-pro-BNP level, ECW%, LVMI, and LV ejection fraction in CAPD patients were 3924 (240 – 74460) pg/mL, 36.7% ± 2.2%, 158 ± 48 g/m2, and 60.5% ± 11.2%, respectively. ( 2 ) Patients were divided into three tertiles (10 patients each) according to their serum NT-pro-BNP concentration [1st tertile 1168 (240 – 2096), 2nd tertile 4856 (2295 – 20088), 3rd tertile 35012 (20539 – 74460) pg/mL]. The tertiles did not differ significantly in terms of age, sex, presence of DM, body mass index, or PD duration. Patients in the 3rd tertile (highest serum NT-pro-BNP concentration) had the highest LVMI (126 ± 45 vs 160 ± 41 vs 200 ± 23 g/m2 for 1st, 2nd, 3rd tertiles, respectively) and the lowest LV ejection fraction (66% ± 11% vs 62% ± 6% vs 55% ± 9%). ECW% did not differ significantly between tertiles (35.5% ± 2.0% vs 37.5% ± 2.0% vs 36.5% ± 2.0%). ( 3 ) In CAPD patients, serum NT-pro-BNP levels correlated positively with LVMI ( r = 0.628, p = 0.003) and negatively with LV ejection fraction ( r = –0.479, p = 0.033). Serum NT-pro-BNP levels did not correlate with ECW% ( r = 0.227, p = 0.25). ( 4 ) Stepwise regression analysis showed that LV ejection fraction (b = -0.610, p = 0.015) and LVMI (b = 0.415, p = 0.007) were independently associated with the serum NT-pro-BNP concentration. Conclusions There was no link between ECW% and serum NT-pro-BNP concentration. Thus, serum NT-pro-BNP levels may not provide objective information with respect to pure hydration status in CAPD patients. In contrast, serum NT-pro-BNP levels were linked to LVMI and LV ejection fraction in CAPD patients. Therefore, while the serum NT-pro-BNP concentration might not be a useful clinical marker for extracellular fluid volume load, it appears useful for evaluating LV hypertrophy and LV dysfunction in CAPD patients.

scholarly journals Comparison of N-Terminal Pro B-Natriuretic Peptide and Echocardiographic Indices in Patients with Mitral Regurgitation

2010 ◽  
Vol 4 ◽  
pp. CMC.S6062
Author(s):  
Shokoufeh Hajsadeghi ◽  
Niloufar Samiei ◽  
Masoud Moradi ◽  
Maleki Majid ◽  
Ladan Kashani ◽  
...  
Keyword(s):  
Plasma Level ◽  
Serum Level ◽  
Mitral Regurgitation ◽  
Natriuretic Peptide ◽  
Doppler Echocardiography ◽  
Performance Index ◽  
Left Ventricular ◽  
Myocardial Performance ◽  
Lv Dysfunction ◽  
Dead End

Introduction Echocardiographic indices can form the basis of the diagnosis of systolic and diastolic left ventricular (LV) dysfunction in patients with Mitral regurgitation (MR). However, using echocardiography alone may bring us to a diagnostic dead-end. The aim of this study was to compare N-Terminal pro B-natriuretic peptide (BNP) and echocardiographic indices in patients with mitral regurgitation. Methods 2D and Doppler echocardiography and BNP serum level were obtained from 54 patients with organic mild, moderate and severe MR. Results BNP levels were increased with symptoms in patients with mitral regurgitation (NYHAI: 5.7 ± 1.1, NYHAII: 6.9 ± 1.5, NYHAIII: 8.3 ± 2 pg/ml, P < 0.001). BNP plasma level were significantly correlated with MPI (myocardial performance index) (r = 0.399, P = 0.004), and following echocardiographic indices: LVEDV (r = 0.45, P < 0.001), LVESV (r = 0.54, P < 0.001), LVEDD (r = 0.48, P < 0.001), LVESD (r = 0.54, P < 0.001), dp/dt (r = −0.32, P = 0.019) and SPAP (r = 0.4, P = 0.006). Conclusion The present study showed that BNP may be useful in patients with MR and may confirm echocardiographic indices.

Abstract 13650: Microrna Signatures in the Transition From Left Ventricular Hypertrophy to Cardiac Dysfunction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Melissa Swinnen ◽  
Hadewich Hermans ◽  
Mattia Quattrocelli ◽  
Peter Pokreisz ◽  
Hilde Gillijns ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cardiac Dysfunction ◽  
Ventricular Hypertrophy ◽  
Expression Patterns ◽  
Left Ventricular ◽  
Luciferase Assay ◽  
Compensatory Response ◽  
Lv Dysfunction ◽  
The Impact

Purpose: Left ventricular hypertrophy (LVH) is not just a compensatory response to increased biomechanical stress but is often associated with unfavorable outcome in patients. Mechanisms that govern transition from subclinical LVH to LV dysfunction are incompletely understood. Lately, single microRNAs (miRs), a class of small non-coding RNAs, have been implicated in LVH, but the expression dynamics and their role in transition to LV dysfunction remain unknown. Methods: We subjected mice to transverse aortic constriction (TAC) for 2, 4 and 10 weeks(wks) or to Ang-2 infusion for 4wks. Cardiac function was examined using serial echocardiography (TTE) and compared to sham mice (SH). MiR profiles in LV tissue were studied using the Nanostring platform, with significant differences between TAC or Ang2 vs SH set at a >2 up-or down-regulation with p<0.01. Western blotting and luciferase assay were performed for target confirmation. The impact of up-regulated miRs was validated in vivo by administration of specific AntagomiR vs Scrambled miRs (SCR) after TAC. Results-TTE showed a modest increase in LV end-systolic dimensions and a decline in fractional shortening (FS) after 4wks TAC and Ang2 . However, after 10wks TAC, LV dilation was present together with a reduction in FS (table1). Cardiac miR signatures indicated that 3 miRs were selectively up-regulated when transition to LV dysfunction was present at 10wks TAC. A common target gene for 2 of these up-regulated miRs (miR764-3p and miR-130b-3p) was confirmed. Moreover, in vivo antagomiR treatment for both miRs protected against cardiac dysfunction and fibrosis(table 1). Conclusion: miR analyses show important time- and stressor-dependent dynamic expression patterns during pressure overload. The miR signatures associated with transition from LVH to LV dysfunction and subsequent targeted antagomiR administration may hold promise for future therapy.

Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: a systematic review

Heart ◽  
2018 ◽  
Vol 105 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Jan M Leerink ◽  
Simone J Verkleij ◽  
Elizabeth A M Feijen ◽  
Annelies M C Mavinkurve-Groothuis ◽  
Milanthy S Pourier ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Natriuretic Peptide ◽  
Late Onset ◽  
Childhood Cancer Survivors ◽  
Diagnostic Value ◽  
Left Ventricular ◽  
Lv Dysfunction ◽  
Low Sensitivity ◽  
Fractional Shortening

ObjectiveTo systematically review the literature and assess the diagnostic value of biomarkers in detection of late-onset left ventricular (LV) dysfunction in childhood cancer survivors (CCS) treated with anthracyclines.MethodsWe systematically searched the literature for studies that evaluated the use of biomarkers for detection of LV dysfunction in CCS treated with anthracyclines more than 1 year since childhood cancer diagnosis. LV dysfunction definitions were accepted as an ejection fraction <50% or <55% and/or a fractional shortening <28%, <29% or <30%. Contingency tables were created to assess diagnostic accuracies of biomarkers for diagnosing LV dysfunction.ResultsOf 1362 original studies screened, eight heterogeneous studies evaluating four different biomarkers in mostly asymptomatic CCS were included. In four studies, an abnormal N-terminal pro-B-type natriuretic peptide (NT-proBNP, cut-off range 63–125 ng/L) had low sensitivity (maximally 22%) and a specificity of up to 97% for detection of LV dysfunction. For troponin levels, in five studies one patient had an abnormal troponin value as well as LV dysfunction, while in total 127 patients had LV dysfunction without troponin elevations above cut-off values (lowest 0.01 ng/mL). Two studies that evaluated brain natriuretic peptide and nitric oxide were underpowered to draw conclusions.ConclusionsIn individual studies, the diagnostic value of NT-proBNP for detection of LV dysfunction in CCS is limited. Troponins have no role in detecting late-onset LV dysfunction with cut-off values as low as 0.01 ng/mL. Further study on optimal NT-proBNP cut-off values for rule out or rule in of LV dysfunction is warranted.

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