scholarly journals Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components

2007 ◽  
Vol 156 (6) ◽  
pp. 695-702 ◽  
Author(s):  
I Stoykov ◽  
H C van Beeren ◽  
A F M Moorman ◽  
V M Christoffels ◽  
W M Wiersinga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Left Ventricular ◽  
Cardiac Gene Expression ◽  
Specific Effects ◽  
Cardiac Gene ◽  
The Right ◽  
Different Parts

Objective: In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression. Design: Rats were treated with AM or Dron and the expression of TRα 1, TRα 2, TRβ 1 and several tri-iodothyronine (T3)-regulated genes was studied in different parts of the heart, namely the right atrium (RA), left ventricular wall (LVW) and apex. Methods: Rats were treated for 14 days with 100 mg/kg body weight AM or Dron. The expression of TRα 1, TRα 2, TRβ 1 and T3-regulated genes was studied using real-time PCR and non-radioactive in situ hybridisation. Results: AM and Dron affected TR expression in the RA similarly by decreasing TRα 1 and β 1 expression by about 50%. In the LVW, AM and Dron decreased TRβ 1 and, interestingly, AM increased TRα 1. In the apex, AM also increased TRα 2. The changes seen in T3-dependent gene expression are reminiscent of foetal reprogramming. Conclusion: Taken together, our results indicate that AM and Dron have similar effects on the expression of TR isoforms in the RA, which could partly contribute to their ability to decrease heart rate. On the other hand, the more profound effect of AM appears on TR- and T3-dependent gene expression in the left ventricle suggests foetal reprogramming.

Myoglobin-deficient mice activate a distinct cardiac gene expression program in response to isoproterenol-induced hypertrophy

2010 ◽  
Vol 41 (2) ◽  
pp. 137-145 ◽  
Author(s):  
Andrei Molojavyi ◽  
Antje Lindecke ◽  
Annika Raupach ◽  
Sarah Moellendorf ◽  
Karl Köhrer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Left Ventricular ◽  
Gene Expression Program ◽  
Cardiac Stress ◽  
Cardiac Gene Expression ◽  
Left Ventricular Dilatation ◽  
Cardiac Gene ◽  
Expression Program ◽  
Deficient Mice

Myoglobin knockout mice (myo−/−) adapt to the loss of myoglobin by the activation of a variety of compensatory mechanisms acting on the structural and functional level. To analyze to what extent myo−/− mice would tolerate cardiac stress we used the model of chronic isoproterenol application to induce cardiac hypertrophy in myo−/− mice and wild-type (WT) controls. After 14 days of isoproterenol infusion cardiac hypertrophy in WT and myo−/− mice reached a similar level. WT mice developed lung edema and left ventricular dilatation suggesting the development of heart failure. In contrast, myo−/− mice displayed conserved cardiac function and no signs of left ventricular dilatation. Analysis of the cardiac gene expression profiles using 40K mouse oligonucleotide arrays showed that isoproterenol affected the expression of 180 genes in WT but only 92 genes of myo−/− hearts. Only 40 of these genes were regulated in WT as well as in myo−/− hearts. In WT hearts a pronounced induction of genes of the extracellular matrix occurred suggesting a higher level of cardiac remodeling. myo−/− hearts showed altered transcription of genes involved in carbon metabolism, inhibition of apoptosis and muscular repair. Interestingly, a subset of genes that was altered in myo−/− mice already under basal conditions was differentially expressed in WT hearts under isoproterenol treatment. In summary, our data show a high capacity of myoglobin-deficient mice to adapt to catecholamine induced cardiac stress which is associated with activation of a distinct cardiac gene expression program.

scholarly journals Cardiac gene expression profile in rats with terminal heart failure and cachexia

2005 ◽  
Vol 20 (3) ◽  
pp. 256-267 ◽  
Author(s):  
Maren Wellner ◽  
Ralf Dechend ◽  
Joon-Keun Park ◽  
Erdenechimeg Shagdarsuren ◽  
Nidal Al-Saadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Expression Profile ◽  
Left Ventricular ◽  
Altered Expression ◽  
Cardiac Gene Expression ◽  
Terminal Heart Failure ◽  
Cardiac Gene ◽  
Blood Pressures

About one-half of double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die by age 7 wk of terminal heart failure (THF); the other (preterminal) one-half develop cardiac damage but survive. Our study’s aim was to elucidate cardiac gene expression differences in dTGR-THF compared with dTGR showing compensated cardiac hypertrophy but not yet THF. dTGR treated with losartan (LOS) and nontransgenic rats (SD) served as controls. THF-dTGR body weight was significantly lower than for all other groups. At death, THF-dTGR had blood pressures of 228 ± 7 mmHg (cardiac hypertrophy index 6.2 ± 0.1 mg/g). Tissue Doppler showed reduced peak early (Ea) to late (Aa) diastolic expansion in THF-dTGR, indicating diastolic function. Preterminal dTGR had blood pressures of 197 ± 5 mmHg (cardiac hypertrophy index 5.1 ± 0.1 mg/g); Ea < Aa compared with LOS-dTGR (141 ± 6 mmHg; 3.7±0.1 mg/g; Ea > Aa) and SD (112 ± 4 mmHg; 3.6 ± 0.1 mg/g; Ea > Aa). Left ventricular RNA was isolated for the Affymetrix system and TaqMan RT-PCR. THF-dTGR and dTGR showed upregulation of hypertrophy markers and α/β-myosin heavy chain switch to the fetal isoform. THF-dTGR (vs. dTGR) showed upregulation of 239 and downregulation of 150 genes. Various genes of mitochodrial respiratory chain and lipid catabolism were reduced. In addition, genes encoding transcription factors (CEBP-β, c-fos, Fra-1), coagulation, remodeling/repair components (HSP70, HSP27, heme oxygenase), immune system (complement components, IL-6), and metabolic pathway were differentially expressed. In contrast, LOS-dTGR and SD had similar expression profiles. These data demonstrate that THF-dTGR show an altered expression profile compared with preterminal dTGR.

A role for T lymphocytes in mediating cardiac diastolic function

2005 ◽  
Vol 289 (2) ◽  
pp. H643-H651 ◽  
Author(s):  
Qianli Yu ◽  
Ronald R. Watson ◽  
John J. Marchalonis ◽  
Douglas F. Larson
Keyword(s):  
Gene Expression ◽  
Diastolic Function ◽  
Immune Modulation ◽  
Expression Patterns ◽  
Relative Proportion ◽  
Wall Stress ◽  
Left Ventricular ◽  
Lymphocyte Function ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

The induction of T helper (TH) lymphocytes by distinct TH ligands results in a differentiation to TH1/TH2 subsets based on their unique pattern of cytokine secretion and effector functions. We hypothesized that the relative proportion of TH1/TH2 directly relates to cardiac fibroblast (CF) function and thereby cardiac extracellular matrix (ECM) composition and cardiac diastolic function in the absence of injury or altered wall stress. We compared the effect of selective TH1 with TH2 inducers on cardiac gene expression, ECM composition, and diastolic function in C57BL/J mice. Twelve weeks after immune modulation, the left ventricular stiffness (β) was significantly increased in the TH1 group and decreased in the TH2 group ( P < 0.01). The TH2 group also demonstrated significantly increased end-diastolic and end-systolic volumes ( P < 0.01). Cardiac gene expression patterns for pro-matrix metalloproteinase (MMP)-9 and -13 were increased by greater than fivefold in the TH2 group and significantly decreased in the TH1 group ( P < 0.05). The total cardiac collagen and cross-linked collagen were significantly increased in the TH1 group and decreased in the TH2 group ( P < 0.01). Coculturing lymphocytes harvested from the treated mice with naive primary CF demonstrated a direct control of the lymphocytes on CF pro-collagen, pro-MMP gene expression, and MMP activity. These results suggest that the TH phenotype differentially affects diastolic function through modulating CF pro-collagen and pro-MMP gene expression, MMP activity, and cardiac collagen cross-linking, resulting in altered ECM composition. Thus modulation of TH lymphocyte function could promote adaptive remodeling in heart failure and postmyocardial infarction.

scholarly journals Resistance to Thyroid Hormone and Cardiovascular Risk

2010 ◽  
Vol 06 ◽  
pp. 77
Author(s):  
Irene Campi ◽  
Deborah Mannavola ◽  
Paolo Beck-Peccoz ◽  
◽  
◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Thyroid Stimulating Hormone ◽  
Hormone Deficiency ◽  
Wild Type ◽  
Large Variability ◽  
Resistance To Thyroid Hormone ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of impaired tissue responsiveness to thyroid hormones (TH) characterised by high circulating TH in the presence of unsuppressed thyroid-stimulating hormone (TSH). TH achieve their action on the heart chiefly via thyroid hormone receptor alpha 1 (TRa1), which is the TH receptor (TR) isoform predominantly expressed in such an organ. Data derived from animal models suggest that in RTH the overstimulation of the TRa1 pathway by the high TH levels could explain the cardiovascular abnormalities seen in these animals, although the discordant cardiac gene expression profile between wild-type (wt) and transgenic mice treated with triiodothyronine (T3) imply that the effects of RTH on the heart are complex and not completely explicable by the heightened T3/TRa1 signalling. To date, only a few studies have evaluated cardiovascular risk in RTH, with conflicting results, confirming the large variability of the RTH phenotype. In particular, some reports show that several cardiovascular parameters seem to move towards hyperthyroidism, while others show a pattern that resembles thyroid hormone deficiency. Finally, recent data suggest that in addition to reduced vascular compliance and echocardiographic abnormalities, RTH subjects may exhibit some features of metabolic syndrome, suggesting an overall increased cardiometabolic risk in this disorder.

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