scholarly journals Developmental and lifelong dioxin exposure induces measurable changes in cardiac structure and function in adulthood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew de Gannes ◽  
Sheryl E. Koch ◽  
Alvaro Puga ◽  
Jack Rubinstein
Keyword(s):  
Later Life ◽  
Continuous Exposure ◽  
Ang Ii ◽  
Left Ventricle Mass ◽  
Aryl Hydrocarbon ◽  
End Diastolic Volume ◽  
Gene Ablation ◽  
Genetic And Environmental Factors ◽  
Dioxin Exposure ◽  
And Function

AbstractCongenital heart disease (CHD) is the most common congenital abnormality. A precise etiology for CHD remains elusive, but likely results from interactions between genetic and environmental factors during development, when the heart adapts to physiological and pathophysiological conditions. Further, it has become clearer that early exposure to toxins that do not result in overt CHD may be associated with adverse cardiac outcomes that are not manifested until later life. Previously, interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, was shown to cause structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. Here, we show that continuous exposure to TCDD from fertilization throughout adulthood caused male mice to underperform at exercise tolerance tests compared to their control and female counterparts, confirming previous observations of a sexually dimorphic phenotype. Renin-angiotensin stimulation by angiotensin II (Ang II) caused measurable increases in blood pressure and left ventricle mass, along with decreased end diastolic volume and preserved ejection fraction. Interestingly, TCDD exposure caused measurable reductions in the myocardial hypertrophic effects of Ang II, suggesting that endogenous AHR signaling present in adulthood may play a role in the pathogenesis of hypertrophy. Overall, the findings reported in this pilot study highlight the complex systems underlying TCDD exposure in the development of cardiac dysfunction in later life.

Associations between life-course frailty and later-life heart size and function in the 1946 NSHD British birth cohort-an epidemiological study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.C Topriceanu ◽  
J.C Moon ◽  
R Hardy ◽  
A.D Hughes ◽  
N Chaturvedi ◽  
...  
Keyword(s):  
Life Course ◽  
Birth Cohort ◽  
Frailty Index ◽  
Later Life ◽  
Left Ventricular ◽  
Step Change ◽  
Deficit Accumulation ◽  
Heart Size ◽  
And Function ◽  
The Life Course

Abstract Background Cardiovascular diseases are an important component of the multi-morbidity syndrome which is associated with negative health outcomes resulting in a major societal economic burden. An objective way to assess multi-morbidity is to calculate a frailty index based on medical deficit accumulation. Late-life frailty has been validated to predict mortality, but little is known about the association between life-course frailty and cardiovascular health in later-life. Purpose To study the association between life-course frailty and later-life heart size and function using data from the world's longest running birth cohort with continuous follow-up. Methods A 45-deficit frailty index (FI) was calculated at 4 age-intervals across the life-course (0 to 16 years old, 19 to 44 years old, 45 to 54 years old and 60 to 64 years old) in participants from the UK 1946 Medical Research Council (MRC) National Survey of Heath and Development (NSHD) birth cohort. The life-course frailty indices (FI0_16, FI19_44, FI45_54 and FI60_64) reflect the cumulative medical deficits at the corresponding age-intervals. They were used to derive FImean and FIsum reflecting overall-life frailty. The step change in deficit accumulation between age-intervals was also calculated (FI2-1, FI3-1, FI4-1, FI3-2, FI4-2, FI4-3). Echocardiographic data at 60–64 years provided: E/e' ratio, ejection fraction (EF), myocardial contraction fraction index (MCFi) and left ventricular mass index (LVmassi). Generalized linear mixed models with gamma distribution and log link assessed the association between FIs and echo parameters after adjustment for sex, socio-economic position and body mass index. Results 1.805 NSHD participants were included (834 male). Accumulation of a single deficit had a significant impact (p<0.0001 to p<0.049) on LVmassi and MCFi in all the life-course FIs and overall FIs. LVmassi increased by 0.89% to 1.42% for the life-course FIs and by 0.36%/1.82% for FIsum and FImean respectively. MCFi decreased by 0.62% to 1.02% for the life-course FIs and by 0.33%/ 1.04%. for FIsum and FImean respectively. One accumulated deficit translated into higher multiplicative odds (13.2 for FI60-64, 2.1 for FI4-1, 75.4 for FI4-2 and 78.5 for FI4-3) of elevated filling pressure (defined as E/e' ratio >13, p<0.0.005 to p<0.02).A unit increase in frailty decreased LV EF (%) by 11%/12% for FI45-54 and FI60-64 respectively, by 10% to 12% for FI2-1, FI3-1, FI4-1 and FI4-2, and 4%/15% for FIsum and FImean respectively (p<0.0014 to p<0.044). Conclusion Frailty during the life-course, overall life-frailty and the step change in deficit accumulation is associated with later-life cardiac dysfunction. Frailty strain appears to have its greatest impact on pathological myocardial hypertrophy (high LVmassi and low MCFi) potentially paving the way to later-life systolic or diastolic dysfunction in susceptible individuals. Funding Acknowledgement Type of funding source: None

Sexual Health and Function in Later Life: A Population-Based Study of 606 Older Adults with a Partner

2015 ◽  
Vol 23 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Vicki Wang ◽  
Colin A. Depp ◽  
Jennifer Ceglowski ◽  
Wesley K. Thompson ◽  
David Rock ◽  
...  
Keyword(s):  
Older Adults ◽  
Sexual Health ◽  
Later Life ◽  
Population Based ◽  
Population Based Study ◽  
And Function

Abstract P135: Hyperpolarized Carbon-13 Magnetic Resonance Reveals Early- and Late-Onset Changes to Metabolism in the Failing Heart

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Marie Schroeder ◽  
Angus Z Lau ◽  
Albert P Chen ◽  
Jennifer Barry ◽  
Damian J Tyler ◽  
...  
Keyword(s):  
Heart Failure ◽  
Magnetic Resonance ◽  
Late Onset ◽  
Krebs Cycle ◽  
Left Ventricular ◽  
Cine Mri ◽  
Cardiac Structure ◽  
End Diastolic Volume ◽  
Myocardial Energetics ◽  
And Function

Disordered metabolic substrate utilisation has been implicated in the pathogenesis of heart failure (HF). Hyperpolarised (HYP) 13C magnetic resonance, a technique in which the fate of 13C-labelled metabolites can be followed using MR imaging or spectroscopy, has enabled non-invasive assessment of metabolism. The aim of this study was to monitor carbohydrate metabolism alongside cardiac structure, function, and energetics, throughout HF progression. HF was induced in pigs (n=5) by right ventricular pacing at 188 bpm for 5 weeks. Pigs were examined at weekly time points: cine MRI assessed cardiac structure and function, HYP 13C2-pyruvate was administered intravenously and 13C MRS was used to assess 13C-glutamate production via Krebs cycle, 31P MRS assessed myocardial energetics, and HYP 13C1-pyruvate was administered to enable MRI of H13CO3- production from pyruvate dehydrogenase (PDH). At baseline, pigs had a normal left ventricular (LV) cardiac index (CI) and end diastolic volume (EDVi). The PCr/ATP was 2.3 ± 0.2. The 13C-glutamate/13C2-pyruvate was 4.3 ± 0.9%, and the H13CO3-/13C1-pyruvate ratio was 1.6 ± 0.2%. After 1–2 weeks of pacing, CI decreased to 3.3 ± 0.5 l/min/m2, PCr/ATP decreased to 1.7 ± 0.1, and 13C-glutamate/13C2-pyruvate decreased to 2.1 ± 0.6%. With the onset of HF, EDVi increased to 140.3 ± 14.1 ml/m2 and H13CO3-/13C1-pyruvate decreased to 0.5 ± 0.2%. In conclusion, we observed an early defect in Krebs' cycle that occurred alongside impaired cardiac energetics and function. Carbohydrate oxidation via PDH was maintained until the onset of HF. These results encourage use of metabolic therapies to delay/prevent the onset of heart failure in patients.

Abstract 445: A Pro-Fibrotic Role of Interleukin-4 in Cardiac Remodeling and Dysfunction

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Hongmei Peng ◽  
Oscar Carretero ◽  
Xiao-Ping Yang ◽  
Pablo Nakagawa ◽  
Jiang Xu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Interleukin 4 ◽  
Ang Ii ◽  
Collagen Production ◽  
And Function ◽  
First Time ◽  
Mini Pump

Elevated interleukin-4 (IL-4) levels are positively related to cardiac fibrosis in heart failure and hypertension. Using Balb/c exhibiting high circulating IL-4, Balb/c- Il4 tm2Nnt (IL-4 knockout with Balb/c background, IL-4 -/- ) and C57BL/6 mice, as well as cultured cardiac fibroblasts (CFs), we hypothesized that 1) high levels of IL-4 result in cardiac fibrosis, making the heart susceptible to angiotensin II (Ang II)-induced damage, and 2) IL-4 potently stimulates collagen production by CFs. Each strain (9- to 12-week old male) received vehicle or Ang II (1.4 mg/kg/day, s.c. via osmotic mini-pump) for 8 weeks. Cardiac fibrosis and function were determined by histology and echocardiography, respectively. Compared to C57BL/6, Balb/c mice had doubled interstitial collagen in the heart, enlarged left ventricle and decreased cardiac function along with elevated cardiac IL-4 protein (1.00±0.08 in C57BL/6 vs 2.61±0.46 in Balb/c, p <0.05); all those changes were significantly attenuated in IL-4 -/- (Table 1). Ang II further deteriorated cardiac fibrosis and dysfunction in Balb/c; these detrimental effects were attenuated in IL-4 -/- , although the three strains had a similar level of hypertension. In vitro study revealed that IL-4Rα was constitutively expressed in CFs (Western blot), and IL-4 potently stimulated collagen production by CFs (hydroxproline assay, from 18.89±0.85 to 38.81±3.61 μg/mg at 10 ng/ml, p <0.01). Our study demonstrates for the first time that IL-4, as a potent pro-fibrotic cytokine in the heart, contributes to cardiac fibrotic remodeling and dysfunction. Thus IL-4 may be a potential therapeutic target for cardiac fibrosis and dysfunction.

William Rutherford Sanders (1828–1881), anatomist, physician, linguist and museum conservator

2018 ◽  
Vol 28 (2) ◽  
pp. 120-123
Author(s):  
Dugald Gardner
Keyword(s):  
Neurological Disorders ◽  
Later Life ◽  
Structure And Function ◽  
Royal Infirmary ◽  
Abdominal Abscess ◽  
General Pathology ◽  
Consultant Physician ◽  
University Of Edinburgh ◽  
And Function ◽  
The University

William Rutherford Sanders spent a childhood and early student days divided between Edinburgh and Montpelier, France before graduating in Medicine in Edinburgh. An early interest in the spleen was encouraged by a two-year period in Europe where he became familiar with the work of Helmholtz, Bernard and Henle. Returning to Edinburgh, his growing experience led to the position of assistant in the Infirmary pathology department. He conducted classes in the University of Edinburgh and on behalf of the Royal Colleges became familiar with the museum of the Royal College of Surgeons where he was chosen as Conservator in 1853. Criticised by 20th century historians for concentrating on verbal teaching rather than on the conservation of the museum, Sanders became a consultant physician to the Royal Infirmary in 1861 and in 1869 Professor of General Pathology. Throughout these years, Sanders gave as much time as possible to the study of the structure and function of the spleen and to neurological disorders such as hemiplegia. His later life was interrupted by a series of illnesses commencing with an abdominal abscess. A prolonged convalescence allowed the resumption of work but deranged vision and hemiplegia preceded his death on 18 February 1881.

scholarly journals Life-course burden of health deficits associates with later-life heart size and function in the 1946 British birth cohort

2020 ◽  
Author(s):  
Constantin-Cristian Topriceanu ◽  
James C Moon ◽  
Rebecca Hardy ◽  
Nishi Chaturvedi ◽  
Alun Hughes ◽  
...  
Keyword(s):  
Life Course ◽  
Birth Cohort ◽  
Later Life ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Heart Size ◽  
Time Periods ◽  
And Function ◽  
The Life Course ◽  
Myocardial Contraction Fraction

Aim: To study the association between the life course accumulation of health deficits and later life heart size and function using data from the 1946 National Survey of Heath and Development (NSHD) British birth cohort, the longest running birth cohort with continuous follow up in the world. Methods and Results: A multidimensional health deficit index (DI) looking at 45 health deficits was serially calculated at 4 time periods of the life course in NSHD participants (0 to 16, 19 to 44, 45 to 54 and 60 to 64 years), and from these the mean and total DI for the life course was derived (DImean, DIsum). The step change in deficit accumulation from one time period to another was also calculated. Echocardiographic data at 60-64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCFi) and E/e. Generalized linear models assessed the association between DIs and echocardiographic parameters after adjustment for sex, socioeconomic position and body mass index. 1,375 NSHD participants were included (46.47% male). For each single new deficit accumulated at any one of the 4 time periods of the life course, LVmassi increased by 0.91 to 1.44% (p<0.013), while MCFi decreased by 0.6 to 1.02% (p<0.05 except at 45 to 54 years). One unit increase in DI at age 45 to 54 and 60 to 64 decreased LV EF by 11 to 12% (p<0.013). A single deficit step change occurring between 60-64 years and one of the earlier time periods, translated into significantly higher odds (2.1 to 78.5, p<0.020) of elevated LV filling pressure defined as E/e>13. Conclusion: The accumulation of health deficits at any time period of the life course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function. The burden of health deficits appears to strain the myocardium potentially leading to future cardiac dysfunction. Keywords: frailty; cardiovascular disease; ejection fraction; left ventricular mass index; myocardial contraction fraction; E/e.

scholarly journals Environmental pollutants-dependent molecular pathways and carcinogenesis

Biodiscovery ◽  
2019 ◽  
Vol 22 ◽  
Author(s):  
Myriam El Helou ◽  
Pascale A. Cohen ◽  
Mona Diab-Assaf ◽  
Sandra Ghayad
Keyword(s):  
Gene Expression ◽  
Environmental Pollutants ◽  
Environmental Chemicals ◽  
Gene Repair ◽  
Hormone Production ◽  
Aryl Hydrocarbon ◽  
Repair Mechanisms ◽  
Cellular Signal ◽  
And Function ◽  
G Protein Coupled

Exposure to environmental pollutants can modulate many biological and molecular processes such as gene expression, gene repair mechanisms, hormone production and function and inflammation, resulting in adverse effects on human health including the occurrence and development of different types of cancer. Carcinogenesis is a complex and long process, taking place in multiple stages and is affected by multiple factors. Some environmental molecules are genotoxic, able to damage the DNA or to induce mutations and changes in gene expression acting as initiators of carcinogenesis. Other molecules called xenoestrogens can promote carcinogenesis by their mitogenic effects by possessing estrogenic-like activities and consequently acting as endocrine disruptors causing multiple alterations in cellular signal transduction pathways. In this review, we focus on recent research on environmental chemicals-driven molecular functions in human cancers. For this purpose, we will be discussing the case of two receptors in mediating environmental pollutants effects: the established nuclear receptor, the Aryl hydrocarbon receptor (AhR) and the emerging membrane receptor, G-protein coupled estrogen receptor 1 (GPER1).

scholarly journals Dioxin Exposure Blocks Lactation through a Direct Effect on Mammary Epithelial Cells Mediated by the Aryl Hydrocarbon Receptor Repressor

2014 ◽  
Vol 143 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Kaitlin J. Basham ◽  
Christopher J. Leonard ◽  
Collin Kieffer ◽  
Dawne N. Shelton ◽  
Maria E. McDowell ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Direct Effect ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Aryl Hydrocarbon ◽  
Dioxin Exposure

scholarly journals Human AML activates the aryl hydrocarbon receptor pathway to impair NK cell development and function

Blood ◽  
2018 ◽  
Vol 132 (17) ◽  
pp. 1792-1804 ◽  
Author(s):  
Steven D. Scoville ◽  
Ansel P. Nalin ◽  
Luxi Chen ◽  
Li Chen ◽  
Michael H. Zhang ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Nk Cell ◽  
Cell Development ◽  
Aryl Hydrocarbon ◽  
Key Points ◽  
And Function

Key Points Human and murine AML activate the AHR pathway, which can regulate miR-29b expression and impair NK cell development and function. AML-induced impairment of NK cell development and function can be reversed with AHR antagonist.

Sign in / Sign up

Export Citation Format

Share Document