Gene expression of the Na-Ca exchangerin cardiac hypertrophy

Menick, Donald R.; Barnes, Kimberly V.; Dawson, Myra; Kent, Robert L.; Cooper, George

doi:10.1016/s1071-9164(96)80061-3

Cited by 12 publications

(7 citation statements)

References 34 publications

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“…Differential regulation. In the hypertrophied rat myocardium, Na ϩ /Ca 2ϩ exchanger mRNA abundance increased consistent with results from other hypertrophy models (14,19,25,26). In our model, Na ϩ /Ca 2ϩ exchanger (NCX1) mRNA expression increased significantly relative to GAPDH not only in the hypertrophy ϩ vehicle group but also in the control ϩ ramipril and hypertrophy ϩ ramipril groups.…”

Section: Discussionsupporting

confidence: 89%

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy

Boateng¹,

Naqvi

Koban³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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Rapid cooling contractures were used in this study to test whether low-dose ramipril improves sarcoplasmic reticulum (SR) Ca(2+) uptake and Na(+)/Ca(2+) exchanger function in isolated hypertrophied rat myocytes. Compensated cardiac hypertrophy was induced by abdominal aortic constriction for 5 wk followed by administration of ramipril (50 microg x kg(-1) x day(-1)) or vehicle for 4 wk. Myocyte cell length and cell width were significantly (P < 0.05) increased in both hypertrophied groups (+/-ramipril). Myocytes were loaded with indo 1, and relaxation was investigated after rapid cooling. Hypertrophied myocyte relaxation in Na(+)-free/Ca(2+)-free solution was 63% slower (P < 0.01) and the fall in intracellular Ca(2+) was 60% slower (P < 0.05) than the relaxation of control cells. After ramipril treatment both relaxation and the decline in intracellular Ca(2+) returned to control rates through improved SR Ca(2+)-ATPase function. Relaxation in caffeine showed no change after hypertrophy; however, after ramipril treatment the time to 50% relaxation in caffeine decreased by 30% (P < 0.05). The improvement in Ca(2+) extrusion across the sarcolemmal membrane occurred independently of changes in Na(+)/Ca(2+) exchanger mRNA and protein abundance. These data demonstrate that ramipril improves both SR-dependent and non-SR-dependent calcium cycling after established cardiac hypertrophy. However, the improvements in function are independent of transcriptional activation and likely to involve altered intracellular ion concentrations.

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Section: Discussionsupporting

confidence: 89%

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy

Boateng¹,

Naqvi

Koban³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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“…Northern analysis of NCX1 mRNA in the LV revealed both the full-length 7-kb transcript and the 1.8-kb band that we and others have reported. 32,33 Unlike the transcript found in the cat, the 1.8-kb transcript was more abundant in the mouse. Importantly, transcript levels of both the 7-kb and 1.8-kb species increased significantly in hearts after 48 hours of pressure overload compared with the control condition ( Figure 4A).…”

Section: Response Of the Transgene To Pressure Overloadmentioning

confidence: 78%

Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na ⁺ -Ca ²⁺ Exchanger Gene H1-Promoter in a Transgenic Mouse Model

Müller

Isomatsu

Koushik

et al. 2002

Circulation Research

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Abstract-The NCX1 gene contains three promoters (H1, K1, and Br1), and as a result of alternative promoter usage and alternative splicing, there are multiple tissue-specific variants of the Na ϩ -Ca 2ϩ exchanger. We have proposed that for NCX1, the H1 promoter regulates expression in the heart, the K1 promoter regulates expression in the kidney, and the Br1 promoter regulates expression in the brain as well as low-level ubiquitous expression. Here, using a transgenic mouse model, we test the role of the DNA region including Ϫ1831 to 67 bp of intron 1, encompassing exon H1 of the feline NCX1 gene (NCX1H1). The NCX1H1 promoter was sufficient for driving the normal spatiotemporal pattern of NCX1 expression in cardiac development. The luciferase reporter gene was expressed in a heart-restricted pattern both in early embryos (embryonic days 8 to 14) and in later embryos (after embryonic day 14), when NCX1 is also expressed in other tissues. In the adult, no luciferase activity was detected in the kidney, liver, spleen, uterus, or skeletal muscle; minimal activity was detected in the brain; and very high levels of luciferase expression were detected in the heart. Transverse aortic constriction-operated mice showed significantly increased left ventricular mass after 7 days. In addition, there was a 2-fold upregulation of NCX1H1 promoter activity in the left ventricle in animals after 7 days of pressure overload compared with both control and sham-operated animals. This work demonstrates that the NCX1H1 promoter directs cardiac-specific expression of the exchanger in both the embryo and adult and is also sufficient for the upregulation of NCX1 in response to pressure overload.

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“…Since it has been shown that ET‐1 is involved in induction of myocardial hypertrophy and heart failure ( Sakai et al ., 1996 ; Colucci, 1997 ), and that the expression of cardiac Na + /Ca 2+ exchanger is increased during cardiac hypertrophy ( Kent et al ., 1993 ; Menick et al ., 1996 ) and failing human heart ( Studer et al ., 1994 ; Flesch et al ., 1996 ), KB‐R7942 may have potential to be a useful pharmacological tool to analyse the pathophysiological relevance of ET‐1 in relation to activation of Na + /Ca 2+ exchanger under these cardiac disorders.…”

Section: Discussionmentioning

confidence: 99%

Role of Na⁺/Ca²⁺ exchange in endothelin‐1‐induced increases in Ca²⁺ transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB‐R7943

Yang

Sakurai

Sugawara

et al. 1999

British J Pharmacology

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1 The e ects of endothelin-1 (ET-1) on intracellular Ca 2+ ion level and cell contraction were simultaneously investigated in rabbit ventricular cardiac myocytes loaded with indo-1/AM. The role of Na + /Ca 2+ exchange in ET-1-induced positive inotropic e ect (PIE) was examined by using phenyl]ethyl]isothiourea methanesulphonate), a selective inhibitor of reverse mode Na + /Ca 2+ exchange. 2 ET-1 at 0.3 pM ± 1 nM increased cell contraction and Ca 2+ transient (CaT) with EC 50 values of 2.9 pM and 1.2 pM, respectively, and the increase in amplitude of CaT was much smaller relative to the PIE: ET-1 at 1 nM increased peak cell shortening by 237%, while it increased peak CaT by 167%. For a given level of PIE, ET-1-induced increase in CaT was much smaller than that induced by elevation of [Ca 2+ ] o and by isoprenaline. Therefore, ET-1 shifted the relationship between peak CaT and cell shortening to the left relative to the relationship for increase in [Ca 2+ ] o , an indication that ET-1 increased myo®brillar Ca 2+ sensitivity. 3 KB-R7943 at 0.1 mM and higher inhibited contraction and CaT induced by 0.1 nM ET-1 and at 0.3 mM it abolished the increase in CaT while inhibiting the PIE by 48.1%. Over concentration range of 0.1 ± 0.3 mM, KB-R7943 neither inhibited baseline contraction and CaT nor the isoprenalineinduced response, although at 1 mM and higher it had a signi®cant inhibitory action on these responses. 4 These results indicate that in rabbit ventricular myocytes both increases in CaT and myo®brillar Ca 2+ sensitivity contribute to the ET-induced PIE, and the activation of reverse mode Na + /Ca 2+ exchange may play a crucial role in increase in CaT induced by ET-1 in rabbit ventricular cardiac myocytes.

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Gene expression of the Na-Ca exchangerin cardiac hypertrophy

Cited by 12 publications

References 34 publications

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy

Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na ⁺ -Ca ²⁺ Exchanger Gene H1-Promoter in a Transgenic Mouse Model

Role of Na⁺/Ca²⁺ exchange in endothelin‐1‐induced increases in Ca²⁺ transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB‐R7943

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Gene expression of the Na-Ca exchangerin cardiac hypertrophy

Cited by 12 publications

References 34 publications

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy

Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy

Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na + -Ca 2+ Exchanger Gene H1-Promoter in a Transgenic Mouse Model

Role of Na+/Ca2+ exchange in endothelin‐1‐induced increases in Ca2+ transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB‐R7943

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Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na ⁺ -Ca ²⁺ Exchanger Gene H1-Promoter in a Transgenic Mouse Model

Role of Na⁺/Ca²⁺ exchange in endothelin‐1‐induced increases in Ca²⁺ transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB‐R7943