Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats.

Meggs, Leonard G.; Tillotson, Joanne Kivela; Huang, Harer; Sonnenblick, Edmund H.; Capasso, J. M.; Anversa, Piero

doi:10.1172/jci114861

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…Possible candidates include the AT 1 angiotensin II receptor subtype and ␣ 1 -adrenergic receptors, which can be upregulated in the presence of ventricular dysfunction and failure. 45,46 We were unable to document that the p53 bands with shifted gel mobility could be further retarded by the addition of p53 antibodies in nuclear extracts from myocytes of normal and paced hearts. This may be a consequence of the level of expression of endogenous p53 in control and stressed myocytes.…”

Section: Pacing-induced Heart Failure and P53mentioning

confidence: 84%

Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes

Leri

Liu²,

Malhotra³

et al. 1998

Circulation

105

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Background-Rapid ventricular pacing in dogs is characterized by a dilated myopathy in which myocyte cell death by apoptosis may play a significant role in the impairment of cardiac pump function. However, the molecular mechanisms implicated in the modulation of programmed cell death under this setting remain to be identified. Moreover, questions have been raised on the specificity and sensitivity of the histochemical detection of DNA strand breaks in nuclei by the terminal deoxynucleotidyl transferase (TdT) reaction. Methods and Results-Changes in the expression of Bcl-2 and Bax and their transcriptional regulator, p53, were determined by Western blot analysis in myocytes isolated from dogs affected by pacing-induced heart failure. A mobility shift assay for p53 binding activity was also performed. In addition, apoptosis was measured by confocal microscopy, which allowed the simultaneous detection of chromatin alterations and DNA damage. p53 DNA binding activity to the bax promoter was increased in nuclear extracts from myocytes obtained from failing hearts, and this response was associated with enhanced expression of Bax protein, 52%, and attenuation of Bcl-2, Ϫ92%. Immunolabeling of p53 in myocyte nuclei, measured by confocal microscopy, was 100% higher in cells from paced hearts. The combination of the TdT assay and confocal microscopy demonstrated that 20 myocyte nuclei per 10 6 were undergoing apoptosis in control myocardium and 4000 per 10 6 after pacing. Moreover, DNA laddering was shown in myocytes by agarose gel electrophoresis of DNA fragments. Conclusions-The activation of p53 and p53-dependent genes may be critical in the modulation of myocyte apoptosis in pacing-induced heart failure. (Circulation. 1998;97:194-203.)

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Section: Pacing-induced Heart Failure and P53mentioning

confidence: 84%

Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes

Leri

Liu²,

Malhotra³

et al. 1998

Circulation

105

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“…Although changes in the half-lives of ATla-R and AT2-R transcripts could not be measured in this study, the results suggested that gene transcription as well as mRNA turnover are enhanced in the infarcted myocardium. Myocardial infarction (46,47), like cardiac hypertrophy, induces the "fetal program" (induction of skeletal a-actin and atrial natriuretic factor) and stimulates expression of the TGF-/31 (48), angiotensinogen (15), and ACE genes (16), suggesting that the synthesis of cardiac Angil is increased in the infarcted heart. Angil can upregulate the expression of the atrial natriuretic factor (49), angiotensinogen (39), and TGF-f31 genes (39) in neonatal rat myocytes by means of an AT1-R mediating mechanism (39).…”

Section: Discussionmentioning

confidence: 99%

Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.

Nio

Matsubara²,

Murasawa³

et al. 1995

J. Clin. Invest.

425

235

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Increasing evidence suggests that angiotensin II (AngHI) acts as a modulator for ventricular remodeling after myocardial infarction. Using competitive reverse-transcriptase polymerase chain reaction, nuclear runoff, and binding assays, we examined the regulation of AngHI type la and lb (ATla-R and ATlb-R) and type 2 receptor (AT2-R) expression in the infarcted rat heart as well as the effects of AngiH receptor antagonists. ATla-R mRNA levels were increased in the infarcted (4.2-fold) and noninfarcted portions (2.2-fold) of the myocardium 7 d after myocardial infarction as compared with those in sham-operated controls, whereas ATlb-R mRNA levels were unchanged. The amount of detectable AT2-R mRNA increased in infarcted (3.1-fold) and noninfarcted (1.9-fold) portions relative to that in the control. The transcription rates for ATla-R and AT2-R genes, determined by means of a nuclear runoff assay, were significantly increased in the infarcted heart. The Angil receptor numbers were elevated (from 12 to 35 fmol/mg protein) in the infarcted myocardium in which the increases in AT1-R and AT2-R were 3.2-and 2.3-fold, respectively, while the receptor affinity was unchanged. Therapy with AT1-R antagonist for 7 d reduced the increase in AT1-R and AT2-R expressions in the infarcted heart together with a decrease in blood pressure, whereas therapy with an AT2-R antagonist did not affect mRNA levels and blood pressure. Neither ATi-R nor AT2-R antagonists affected the infarct sizes. These results demonstrated that myocardial infarction causes an increase in the gene transcription and protein expression of cardiac ATla-R and AT2-R, whereas the ATlb-R gene is unaffected, and that therapy with an AT1-R antagonist, but not with an AT2-R antagonist, is effective in reducing the increased expression of AngII receptor subtypes induced by myocardial infarction. (J. Clin. Invest. 1995.95:46-54.)

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“…7 The reactive hypertrophic growth adaptation of viable myocytes was found to be accompanied by an enhanced norepinephrine-stimulated phosphoinositol turnover and upregulation of the fetal sarcomeric actin isoform.7 These findings provided a construct for the hypothesis that a1-adrenoreceptors, singularly or in concert with other growth-promoting factors, may regulate myocyte hypertrophy. On the other hand, if the a1-adrenoreceptor controls only one component of the changes in myocyte length and diameter, other surface receptors may be implicated in the modulation of myocyte growth.…”

Section: Regulation Of Angiotensin II Receptors On Ventricular Myocytmentioning

confidence: 93%

Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats.

Meggs

Coupet

Huang

et al. 1993

Circulation Research

Self Cite

146

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To determine the effects of acute myocardial infarction on the regulation of angiotensin II (Ang II) receptors and contractile performance of left and right ventricular myocytes, coronary artery ligation was surgically induced in rats, and Ang II receptor density and affinity and the mechanical properties of surviving muscle cells were examined 1 week later. Physiological determinations of cardiac pump function revealed the presence of ventricular failure, which was associated at the cellular level with a depression in the velocity of myocyte shortening and relengthening, a prolongation of time to peak shortening, and a reduction in the extent of cell shortening. These abnormalities in single-cell function were more prominent in left than in right ventricular myocytes. Cellular hypertrophy was documented by increases in cell length and width, which were also greater in the spared myocytes of the infarcted left ventricle. Reactive hypertrophy was accompanied by a 1.84- and 1.85-fold increase in the density of Ang II receptors on left and right myocytes, respectively. On the other hand, the affinity of Ang II receptors for the radiolabeled antagonist was not altered. However, Ang II-stimulated phosphoinositol turnover was enhanced by 3.7- and 2.5-fold in left and right myocytes, respectively, after infarction. Ventricular myocytes were found to possess the AT1 receptor subtype exclusively. In conclusion, myocardial infarction leads to impairment in the contractile behavior of the remaining cells and to the activation of Ang II receptors and effector pathway associated with these receptors, which may be involved in the reactive growth adaptation of the viable myocytes.

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Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats.

Cited by 19 publications

References 35 publications

Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes

Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes

Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.

Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats.

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