Abstract 20385: Pregnancy-Induced Cardiac Hypertrophy is Accompanied by Unique Contractile Properties Not Seen in Other Forms of Physiological Hypertrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jessica Tyrrell ◽  
Kaitlyn Kennard ◽  
Catherine Makarewich ◽  
Beth A Bailey
Keyword(s):  
Cardiac Hypertrophy ◽  
Late Pregnancy ◽  
Calcium Transient ◽  
Contractile Properties ◽  
Receptor Protein ◽  
Ca Channel ◽  
Adrenergic Stimulation ◽  
Twitch Contraction ◽  
Relaxation Phase ◽  
Near Term

Background: Cardiac hypertrophy accompanying pregnancy has generally been categorized as physiologic hypertrophy similar to that seen with exercise, however a reduction in cardiac function in late pregnancy has been suggested. Furthermore, the hemodynamic stress of pregnancy can induce a maladaptive, pathologic hypertrophy in a small number of women. This study seeks to characterize the contractile properties of late-pregnant myocardium. Methods and Results: Late Pregnancy (LP) Female Swiss-Webster mice were bred then studied at near term (Embryonic day 17-19) and compared to age-matched, non-pregnant (NP) controls. Individual cardiac myocytes were isolated using collagenase-based perfusion technique. Two-dimensional Surface Area measured in quiescent cells was elevated (p<.01) in LP myocytes (LPM) (3609± 132u 2 ) vs NP myocytes (NPM) (2736± 88u 2 ), and this increase was due to increases in both length (8.5%) and width (15.6%). Western Blot analysis showed a reduction in Ryanodine Receptor protein in LP, but no differences in L-type Ca Channel, SERCA or Phospholamban levels. Sarcomere length (light diffraction) and Ca 2+ transients (fluo-3) were measured at pacing rates of 1 Hz and at bath [Ca] of 2mM. Duration of twitch contraction was prolonged (p<.05) in LPM as measured by Time to 75% Recovery (.42 ± .02 vs .37 ±.01 sec in NPM) and Time to 90% recovery (.51 ± .02 vs .45 ± .02 sec in NPM). There were no differences in other contractile parameters measured or in the fluo-3 calcium transient properties. 10 -7 M Isoproterenol (ISO) was used to determine the responsiveness to adrenergic stimulation. ISO induced significantly enhanced contractility in both LPM and NPM, and the response was heightened in LPM such that the presence of ISO normalized the differences in the duration of twitch contraction between LPM and NPM. Conclusions: These results suggest that hypertrophied LPM have characteristics of both physiologic and pathologic hypertrophy including enhanced responsiveness to ISO and a prolonged relaxation phase. The prolongation of relaxation is not seen in physiologic hypertrophy induced by exercise and may contribute to the diastolic dysfunction reported in some pregnancies. Enhanced response to ISO suggests an increased cardiac reserve in LPM.

Effect of pregnancy on rat myometrial β2-adrenoceptor mRNA and isoproterenol-induced relaxation of isolated uterine strips

1997 ◽  
Vol 153 (3) ◽  
pp. 393-399 ◽  
Author(s):  
T Engstrøm ◽  
P Bratholm ◽  
H Vilhardt ◽  
N J Christensen
Keyword(s):  
De Novo ◽  
Contractile Activity ◽  
Post Partum ◽  
Late Pregnancy ◽  
Maximal Effect ◽  
Adrenergic Stimulation ◽  
Pregnant Rats ◽  
Binding Characteristics ◽  
Near Term ◽  
One Way Anova

Abstract The altered myometrial contractile activity near term of pregnancy is partly due to changes in the responsiveness to catecholamines. Previous experiments have basically been concerned with uterine adrenoceptor binding characteristics. In the present study we have evaluated total myometrial DNA, β2-adrenoceptor mRNA and isoproterenol-induced relaxation of rat isolated uterine strips pre-contracted with potassium on days 0, 7, 14 and 21 of pregnancy and on day 5 post-partum. Total myometrial DNA expressed per milligram wet tissue peaked at day 14 of pregnancy followed by a decrease at the end of gestation. This suggests that hyperplasia predominates in the growth of the uterus in early gestation, whereas hypertrophy may be more marked in late pregnancy. The concentration of β2-adrenoceptor mRNA decreased linearly throughout the gestational period (0·73 ± 0·20 amol/mg wet tissue on day 0 vs 0·34 ± 0·09 amol/mg wet tissue on day 21, P<0·05). Five days after parturition, at which time the uterus had returned to its pre-pregnant weight, β2-adrenoceptor mRNA was found to have increased 8-fold (2·79 ± 0·14 amol/mg wet tissue, P<0·05) as compared with day 21. The maximal effect of isoproterenol on pre-contracted uterine strips in which α-receptors were blocked by phentolamine showed a similar decrease which on day 21 reached 67% of the day 0 level (P<0·001). EC50 values were unchanged in all groups except day 21 pregnant rats in which an increase was observed. One-way ANOVA with Bonferroni's t-test showed statistically significant differences only between the day 21 group and either the day 5 post-partum group or the day 14 pregnant group (P<0·05). The observed alteration in EC50 prior to the end of gestation indicates that the system becomes less sensitive to β2-adrenergic stimulation at this time. We conclude that a reduction of de novo synthesis of β2-adrenoceptors may play a role in contributing to the increased myometrial activity at term. We further suggest that the dramatic up-regulation of β2-adrenoceptor mRNA postpartum may protect the fully involuted uterus against excessive contractions induced by oxytocin secreted during lactation. Journal of Endocrinology (1997) 153, 393–399

Inhibition of Matrix Metalloproteinases Prevents Cardiac Hypertrophy Induced by β-Adrenergic Stimulation in Rats

2003 ◽  
Vol 42 (2) ◽  
pp. 174-181 ◽  
Author(s):  
Shoko Miura ◽  
Isao Ohno ◽  
Jun Suzuki ◽  
Ko Suzuki ◽  
Shinji Okada ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Cardiac Hypertrophy ◽  
Adrenergic Stimulation

scholarly journals Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Cyclic ADP-Ribose (cADPR) Mediate Ca2+ Signaling in Cardiac Hypertrophy Induced by β-Adrenergic Stimulation

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0149125 ◽  
Author(s):  
Rukhsana Gul ◽  
Dae-Ryoung Park ◽  
Asif Iqbal Shawl ◽  
Soo-Yeul Im ◽  
Tae-Sik Nam ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Nicotinic Acid ◽  
Adrenergic Stimulation ◽  
Cyclic Adp Ribose

scholarly journals Dihydrotanshinone I Ameliorates Cardiac Hypertrophy in Diabetic Mice Induced by Chronic High-Fat Feeding

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2095260
Author(s):  
Songpei Li ◽  
Xueping Lei ◽  
Zekuan Xiao ◽  
Wenyi Xia ◽  
Chaojin Lin ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Diastolic Dysfunction ◽  
Glycogen Synthase ◽  
Salvia Miltiorrhiza ◽  
High Fat ◽  
Relaxation Phase ◽  
Neonatal Cardiomyocytes ◽  
Extracellular Signal ◽  
Fat Feeding

Salvia miltiorrhiza Bge. (Danshen) is widely used to improve blood circulation and the dredge meridian in traditional Chinese medicine. In the present study, we evaluated the effects of dihydrotanshinone I (DHTS), a natural product from Danshen, on chronic high-fat feeding-induced cardiac remodeling and dysfunction. DHTS (25 mg/kg, intraperitoneal) did not affect blood glucose, insulin levels, and glucose intolerance. However, it alleviated diastolic dysfunction induced by the high-fat diet, as indicated by the increase in the ratio of peak early filling velocity to peak late filling velocity of the mitral and suppression of the extension of the isovolumic relaxation phase of the left ventricle. Further investigations revealed that DHTS ameliorated high-fat induced cardiac hypertrophy in mice and suppressed insulin-induced enlargement of cardiomyocytes in vitro. In neonatal cardiomyocytes, DHTS restored insulin-induced suppression of CCAAT/enhancer-binding protein beta-2 isoform (CEBPβ) and the phosphorylation of glycogen synthase kinase-3β (GSK3β) and extracellular signal-regulated kinase (ERK). Taken together, our results indicated that DHTS ameliorated cardiac hypertrophy and diastolic dysfunction in high-fat-fed mice, probably through the inhibition of insulin-induced suppression of CEBPβ and phosphorylation of GSK3β and ERK in cardiomyocytes.

scholarly journals 3444 Development of human engineered cardiac tissue (hECT)-based screening assay to explore cardiac contractile properties in response to pharmacological challenge with proarrhythmic drugs

2019 ◽  
Vol 3 (s1) ◽  
pp. 8-8
Author(s):  
Francesca Stillitano ◽  
Irene C. Turnbull ◽  
Jaydev Dave ◽  
Jean-Sébastien Hulot ◽  
Roger J. Hajjar
Keyword(s):  
Cardiac Tissue ◽  
Calcium Transient ◽  
Peak Height ◽  
Contractile Properties ◽  
Pronounced Increase ◽  
Cardiac Contractile ◽  
Pharmacological Challenge ◽  
Beat Rate ◽  
Subject Specific ◽  
Sensitive Line

OBJECTIVES/SPECIFIC AIMS: The goals of this study were (1) to evaluate the effect of proarrhythmic drugs on calcium transient and (2) to use three-dimensional human engineered cardiac tissue (hECT) technology to evaluate cardiac contractile properties in response to pharmacological challenge with proarrhythmic drugs. METHODS/STUDY POPULATION: Calcium transient was measured in subject-specific iPSC-CMs by using the IonOptix system in Sotalol treated vs. untreated conditions. We fabricated human engineered cardiac tissues (hECT) in a custom designed bioreactor using low- and high-sentitive subject-specific iPSC-CMs. Contractile function of the hECT was evaluated at baseline and after Sotalol [300 µM] administration. The change in beat rate was recorded under spontaneous beating conditions; changes in other twitch parameters, including time to relaxation, were recorded under electrical stimulation. Time to relaxation served as an indicator of action potential duration (APD), which has a temporal correlation with the QT interval. RESULTS/ANTICIPATED RESULTS: The low-sensitive iPSC-CM showed a considerable drop in overall peak height of the calcium transient, in the presence of 100 µM Sotalol. The high-sensitive line, however, showed a more pronounced drop in peak height. Sotalol treatment also induced a more pronounced increase in the exponential decay time constant (tau) in the high-sensitive line compared to the low-sensitive line. The hECT fabricated with high sensitive hiPSC-CM showed a larger decrease in spontaneous beat rate in response to Sotalol (0.41 vs 0.23 fold decrease), with a higher increase in time to relaxation (1.8 vs 1.3 fold increase), compared to hECT from low sensitive hiPSC-CM. Moreover, while the low-sensitive hECT showed a positive correlation between time to relaxation and developed force, as expected after Sotalol stimulation; the high-sensitive hECT failed to show a positive inotropic response. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest subject-specific iPSC-CMs and hECT, can be used to model functional abnormalities observed in diLQTS in response to Sotalol, and offer novel insights into human-based screening assays for toxic drug reactions. Success of this study may help identify key components underlying diLQT susceptibility to ultimately develop novel therapeutic agents.

scholarly journals Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARγ-dependent autocrine mechanism

2010 ◽  
Vol 299 (3) ◽  
pp. H690-H698 ◽  
Author(s):  
Rajesh H. Amin ◽  
Suresh T. Mathews ◽  
Adebisi Alli ◽  
Todd Leff
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Receptor Gene ◽  
Peroxisome Proliferator ◽  
Adrenergic Stimulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Ppar Γ ◽  
Culture Models

In experimental animal and cell culture models, activation of peroxisome proliferator-activated receptor (PPAR) γ in heart has been shown to have beneficial effects on cardiac function and cardiomyocyte physiology. The goal of this study was to identify the signaling pathway by which PPARγ activation protects cardiomyocytes from the deleterious effects of hypertrophic stimuli. In primary cardiomyocyte cultures, we found that genetic or pharmacological activation of PPARγ protected cells from cardiac hypertrophy induced by α-adrenergic stimulation. Examination of gene expression in these cells revealed a surprising increase in the expression of adiponectin in cardiomyocytes and secretion of the high-molecular-weight form of the hormone into media. Using RNAi to block PPARγ-induced adiponectin production or adiponectin receptor gene expression, we found that the PPARγ-mediated anti-hypertrophic effect required cardiomyocyte-produced adiponectin, as well as an intact adiponectin signaling pathway. Furthermore, mice expressing constitutive-active PPARγ and cardiomyocyte specific adiponectin expression were protected from high-fat diet-induced cardiac hypertrophy and remodeling. These findings demonstrate that functional adiponectin hormone can be produced from the heart and raise the possibility that beneficial effects of PPARγ activation in heart could be due in part to local production of adiponectin that acts on cardiomyocytes in an autocrine manner.

INTRA-UTERINE TISSUES FROM LATE-PREGNANT RHESUS MONKEYS (MACACA MULATTA) PRODUCE 6-OXO-PROSTAGLANDIN F1α IN VITRO

1979 ◽  
Vol 81 (3) ◽  
pp. 339-343 ◽  
Author(s):  
M. D. MITCHELL ◽  
B. R. HICKS ◽  
G. D. THORBURN ◽  
J. S. ROBINSON
Keyword(s):  
Caesarean Section ◽  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Late Pregnancy ◽  
Unit Weight ◽  
Decidua Basalis ◽  
Prostaglandin F ◽  
Near Term

The rates of production of 6-oxo-prostaglandin F1α (6-oxo-PGF1α) in vitro by intra-uterine tissues taken from late-pregnant monkeys at Caesarean section have been determined. For tissues obtained between days 140 and 149 of pregnancy (late pregnancy) the general quantitative order of rates of production (per unit weight) was decidua basalis> placenta > decidua parietalis>amnion>chorion = myometrium. When tissues were taken between days 160 and 168 of pregnancy (near term) this order was placenta > decidua parietalis = amnion> myometrium = decidua basalis > chorion. There was a significant reduction near term in the rate of production of 6-oxo-PGF1α by decidua basalis; all other tissues exhibited similar rates of production at the two gestational periods investigated.

scholarly journals In utero hypoxia altered Ang II-induced contraction via PKCβ in fetal cerebral arteries

2020 ◽  
Vol 244 (1) ◽  
pp. 213-222
Author(s):  
Hongyu Su ◽  
Xueyi Chen ◽  
Yueming Zhang ◽  
Linglu Qi ◽  
Yun He ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cerebral Circulation ◽  
Cerebral Arteries ◽  
Fetal Brain ◽  
Calcium Transient ◽  
In Utero ◽  
Protective Effects ◽  
Ang Ii ◽  
Voltage Dependent ◽  
Near Term

Cerebral circulation is important in fetal brain development, and angiotensin II (Ang II) plays vital roles in regulation of adult cerebral circulation. However, functions of Ang II in fetal cerebral vasculature and influences of in utero hypoxia on Ang II-mediated fetal cerebral vascular responses are largely unknown. This study investigated the effects and mechanisms of in utero hypoxia on fetal middle cerebral arteries (MCA) via Ang II. Near-term ovine fetuses were exposed to in utero hypoxia, and fetal MCA responses to Ang II were tested for vascular tension, calcium transient, and molecular analysis. Ang II caused significant dose-dependent contraction in control fetal MCA. Ang II-induced MCA constriction was decreased significantly in hypoxic fetuses. Neither losartan (AT1R antagonist, 10−5 mol/L) nor PD123,319 (AT2R antagonist, 10−5 mol/L) altered Ang II-mediated contraction in fetal MCA. Phenylephrine-mediated constriction was also significantly weaker in hypoxic fetuses. Bay K8644 caused similar contractions between the two groups. Protein expression of L-type voltage-dependent calcium channels was unchanged. There were no differences in caffeine-mediated vascular tension or calcium transients. Contraction induced by PDBu (PKC agonist) was obviously weaker in hypoxic MCA. Protein expression of PKCβ was reduced in the hypoxic compared with the control, along with no differences in phosphorylation levels. The results showed that fetal MCA was functionally responsive to Ang II near term. Intrauterine hypoxia reduced the vascular agonist-mediated contraction in fetal MCA, probably via decreasing PKCβ and its phosphorylation, which might play protective effects on fetal cerebral circulation against transient hypoxia.

Sign in / Sign up

Export Citation Format

Share Document