Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin

Deten, Alexander

doi:10.1016/j.cardiores.2003.10.026

Cited by 15 publications

(15 citation statements)

References 21 publications

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“…It has been shown that central venous pressure was elevated in EPO-tg6 mice [9]. Cardiac hypertrophy in 8 months old tg6 mice was also documented at the histological level by an increase of myocyte cross sectional area from 495 ± 32 to 644 ± 49 µm 2 (p < 0.05) [10]. In contrast, in rats in which the hematocrit was raised to 0.63 by EPO administration, no hypertrophy of the RV or LV was observed [17,18].…”

Section: Discussionmentioning

confidence: 89%

“…A higher cross-linking rate was postulated, since there was a rise in the activity of lysyl oxidase, which is the enzyme responsible for initiating the formation of cross-links in collagen. The decrease of the relaxation time index of the LV from 2.66 ± 0.11 in wt mice to 2.23 ± 0.14 (p < 0.05) [10] could be a result of the stiffer LV. Nevertheless, the baseline heart function of tg6 mice was not significantly different from wt mice apart from a decreased pressure amplitude in the aorta (wt: 26.6 ± 1.3, tg: 22.1 ± 0.9 mmHg, p < 0.05, [10]) and an increased central venous pressure (wt: 0, tg: 3 ± 2 mmHg, p < 0.05, [9]) in tg6 mice.…”

Section: Discussionmentioning

confidence: 99%

“…However, tg6 mice had a reduced exercise performance [9]. If the mechanism of norepinephrine-stimulation is similar to that of reduced exercise performance in tg6 mice, then myocardial ischemia and ultimately acute heart failure is a typical feature [10].…”

Section: Discussionmentioning

confidence: 99%

“…However, there was no difference in heart function under baseline resting conditions [10]. The reduced exercise-endurance could be explained by acute heart failure since norepinephrine infusion in EPO-tg6 mice led to myocardial ischemia with diastolic dysfunction [10].…”

Section: Introductionmentioning

confidence: 99%

“…The reduced exercise-endurance could be explained by acute heart failure since norepinephrine infusion in EPO-tg6 mice led to myocardial ischemia with diastolic dysfunction [10]. The hearts of tg mice were hypertrophied [9,10]. Hypertrophy of the heart is often associated with cardiac fibrosis [11].…”

Section: Introductionmentioning

confidence: 99%

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cardiac remodeling in Erythropoietin-transgenic mice

Briest

Homagk

Baba³

et al. 2004

Cell Physiol Biochem

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Background: Transgenic (tg) mice with chronic overexpression of the human erythropoietin gene are characterized by an increased hematocrit of about 0.80 in adulthood. This is accompanied by cardiac dysfunction and premature death. The aim of this study was to examine whether this cardiac dysfunction was accompanied by hypertrophy of the heart with remodeling of the extracellular matrix (ECM). Methods: 3-months-old wild type (wt) and tg mice without cardiac hypertrophy were compared with the respective 7-months-old mice. The mRNA of brain natriuretic peptide (BNP), of the matrix metalloproteinases (MMP)-2, -8, -9, -13, of the tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, -4 and of collagen I and III was detected by ribonuclease protection assay. The activity of MMPs was measured by zymography. Results: There was hypertrophy of both ventricles in 7-months-old tg mice, which was accompanied by elevated mRNA expression of BNP. MMP-2 activity was increased and MMP-9 activity was decreased in the left ventricle (LV) of 3-months-old tg mice. This was accompanied by elevated TIMP-4 expression, followed by a shift of collagen mRNA expression from type III to type I in this ventricle. Conclusion: The shift to collagen I in the heart of tg mice might be associated with a stiffer ventricle resulting in diastolic dysfunction. This may be responsible for a relative and intermittent LV- and right ventricle (RV)-insufficiency which was likely to have occurred as evidenced by the elevation of lung and liver weight with hemorrhage and interstitial fibrosis after 7 months..

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