p53-Mediated Upregulation of
            <i>BAX</i>
            Gene Transcription Is Not Involved in Bax-α Protein Overexpression in the Left Ventricle of Spontaneously Hypertensive Rats

Fortuño, María Antonia; Zalba, Guillermo; Ravassa, Susana; D’Elom, Eva; Beaumont, Francisco J.; Fortuño, Ana; Dı́ez, Javier

doi:10.1161/01.hyp.33.6.1348

Cited by 23 publications

(17 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptosis is a strong overall determinant of the cardiac phenotype and is thought to significantly contribute to the progression of heart failure (33). Increased apoptosis has been observed in the myocardium of SHR (8,23) and in other models of hypertrophy (6,11,41). Results of the present study are in accord with these previous reports, as we showed a 100% increase in apoptotic rates in SHR-SED relative to WKY-SED controls (6,8,11,23,41).…”

Section: Discussionsupporting

confidence: 92%

Left ventricular remodeling with exercise in hypertension

Kolwicz

MacDonnell

Renna

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

.-We investigated how exercise training superimposed on chronic hypertension impacted left ventricular remodeling. Cardiomyocyte hypertrophy, apoptosis, and proliferation in hearts from female spontaneously hypertensive rats (SHRs) were examined. Four-month-old SHR animals were placed into a sedentary group (SHR-SED; n ϭ 18) or a treadmill running group (SHR-TRD, 20 m/min, 1 h/day, 5 days/wk, 12 wk; n ϭ 18). Age-matched, sedentary Wistar Kyoto (WKY) rats were controls (n ϭ 18). Heart weight was greater in SHR-TRD vs. both WKY (P Ͻ 0.01) and SHR-SED (P Ͻ 0.05). Morphometricderived left ventricular anterior, posterior, and septal wall thickness were increased in SHR-SED relative to WKY and augmented in SHR-TRD. Cardiomyocyte surface area, length, and width were increased in SHR-SED relative to WKY and further increased in SHR-TRD. Calcineurin abundance was increased in SHR-SED vs. WKY (P Ͻ 0.001) and attenuated in SHR-TRD relative to SHR-SED (P Ͻ 0.05). Protein abundance and mRNA of Akt was not different among groups. The rate of apoptosis was increased in SHR-SED relative to WKY and mitigated in SHR-TRD. The abundance of Ki-67 ϩ cells across groups was not statistically different across groups. The abundance of cardiac progenitor cells (c-Kit ϩ cells) was increased in SHR-TRD relative to WKY. These data suggest that exercise training superimposed on hypertension augmented cardiomyocyte hypertrophy, despite attenuating calcineurin abundance. Exercise training also mitigated apoptosis in hypertension and showed a tendency to enhance the abundance of cardiac progenitor cells, resulting in a more favorable cardiomyocyte number in the exercise-trained hypertensive heart. hypertrophy; myocytes; apoptosis; proliferation CHRONIC HYPERTENSION INDUCES overall cardiac enlargement, which is, in part, due to cardiomyocyte hypertrophy. This is a significant health issue, since pathological cardiac enlargement increases the risk for the development of congestive heart failure (4). Increased apoptosis has also been noted in the hypertensive heart, which may be an integral substrate in overall remodeling and progression to heart failure (33).Several studies have reported that cardiac myocytes are capable of mitotic division and proliferation (13,14). While the control mechanisms for the induction of cardiomyocyte proliferation remain unclear, one theory purports the involvement of a resident population of cardiac progenitor cells (1, 30), which have been shown to increase their activity in stress-induced pathological conditions (1,28,31). In the hypertensive heart, cardiomyocyte proliferation may counteract apoptosis, thus reducing the progressive loss of cardiomyocytes.Recent studies from our laboratory, as well as others, have shown an overall phenotypical improvement for the myocardium with exercise training in hypertension (3,17,24,34,35,42). However, the precise putative mechanisms associated with the observed adaptations with exercise training remain unclear. Our present hypothesis is that exercise training in hypertension ...

show abstract

Section: Discussionsupporting

confidence: 92%

Left ventricular remodeling with exercise in hypertension

Kolwicz

MacDonnell

Renna

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Previous results from our laboratory have shown that long-term pharmacological interference of the renin-angiotensin system prevents the increment of cardiomyocyte apoptosis in adult SHR. 17,21,22 Other groups 18,20 have confirmed these effects in adult SHR and failing aged SHR. In the same experimental model, Tea et al 47 recently analyzed the effects that a 4-week administration of different antihypertensive drugs had on cardiac hypertrophy regression and on the DNA fragmentation index.…”

Section: Effects Of Antihypertensive Drugsmentioning

confidence: 81%

“…We have previously reported that the increment of cardiomyocyte apoptosis in the hypertrophied left ventricle of adult SHR is associated in a temporal way with cardiac ACE activity and that a direct correlation exists between the 2 parameters in hypertensive animals. 17 Moreover, chronic treatment with either an ACE inhibitor or an angiotensin type 1 receptor (AT 1 ) antagonist prevents cardiomyocyte apoptosis in this model, 17,21,22 suggesting that the local renin-angiotensin system activation may be involved in the triggering of cardiomyocyte apoptosis. In this respect, it has been demonstrated that binding of angiotensin II to its AT 1 receptor induces apoptosis of cardiomyocytes isolated from neonatal 23 and adult 24 normotensive rats.…”

Section: Angiotensin IImentioning

confidence: 88%

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

et al. 2001

Self Cite

View full text Add to dashboard Cite

Abstract-Hypertensive heart disease is a progressive condition in which the compensatory left ventricular hypertrophy that maintains cardiac output leads to myocardial remodeling, characterized by fibrosis, insufficient vascularization, and alterations in cardiomyocytes, including contractile disturbances, changes in gene expression, and decrease in the number of cells. Structural abnormalities in the myocardial wall accelerate the development of diastolic and systolic dysfunction, resulting in heart failure. Many observations point to the apoptotic cell death of cardiomyocytes as a relevant factor in the transition from compensatory hypertrophy to pump failure in experimental and human hypertension. Potential inducers of cardiomyocyte apoptosis in overloaded hearts include extrinsic factors, such as mechanical forces, neurohormonal activation, oxidative stress, hypoxia, and cytokines. Some lines of evidence indicate that angiotensin II and the overstretching of cardiomyocytes are originally involved in the triggering of apoptosis in hypertension, whereas other factors are being investigated. Furthermore, intracellular changes, such as downregulation of survival proteins or activation of death proteins, seem to play an important role. The assumption that the apoptosis of cardiomyocytes worsens hypertensive heart disease prognosis brings forth new approaches to avoid or slow the transition to pump failure. In this respect, experimental data indicate that currently used antihypertensive drugs interfere with cardiomyocyte apoptosis. Moreover, the knowledge of intracellular apoptotic processes in cardiomyocytes provides novel therapeutic strategies to be added to the multimodal approach in the prevention of heart failure.

show abstract

“…In agreement, our results support a role of bax in association with cardiomyocyte apoptosis in this in vivo model of ANG II-induced hypertension. However, the study of Fortuno et al (9) showing that apoptosis in spontaneously hypertensive rats is associated with increased Bax-␣ and normal levels of p53 does not support a role of p53, which is a transcriptional regulator of bax and bcl-2 (18) in cardiomyocyte apoptosis in vivo, at least in genetic hypertension. A role of p53 in cardiac apoptosis in the ANG II-induced hypertensive model remains to be investigated.…”

Section: Discussionmentioning

confidence: 98%

Effect of AT₁ receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension

Diep

Mabrouk

Yue

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

sc) for 7 days with or without the AT1 receptor antagonist losartan (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 orally). Cardiac function was assessed by echocardiography. Apoptosis in the heart was detected and quantified by in situ TdT-mediated dUTP nickend labeling (TUNEL) and radiolabeled DNA laddering. Expression of bax, bcl-2, caspase 3, and AT1 and AT2 receptors was examined by Western blot analysis. Activity of caspase 3 was also measured by a fluorometric immunosorbent enzyme assay. Tail cuff systolic blood pressure was elevated (P Ͻ 0.01, n ϭ 6) in ANG II-infused rats (173 Ϯ 3 mmHg) versus controls (111 Ϯ 2 mmHg) and reduced by losartan (134 Ϯ 4 mmHg). Cardiac function was essentially unchanged in ANG II-infused rats. Increased internucleosomal DNA cleavage by TUNEL assay and radiolabeled DNA laddering showed results compatible with enhanced cardiomyocyte apoptosis in the hearts of ANG-II infused rats. The bax-to-bcl-2 ratio, expression of the active form of caspase 3 (17 kDa), and activity of caspase 3 in the hearts of the ANG II group increased more than twofold above controls. Protein expression of AT1 and AT2 receptors was significantly increased in ANG II-infused rats compared with control rats. Losartantreated ANG II-infused rats exhibited normalized apoptosis, bax, caspase 3 activity, and AT1 receptors. ANG II stimulation of AT1 receptors in the heart in vivo is associated with an increased rate of apoptosis without major hemodynamic consequences. Bax and caspase 3 are involved in the apoptotic signaling pathway in this experimental paradigm.caspase; bax; bcl-2

show abstract

p53-Mediated Upregulation of BAX Gene Transcription Is Not Involved in Bax-α Protein Overexpression in the Left Ventricle of Spontaneously Hypertensive Rats

Cited by 23 publications

References 23 publications

Left ventricular remodeling with exercise in hypertension

Left ventricular remodeling with exercise in hypertension

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

Effect of AT₁ receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension

Contact Info

Product

Resources

About

p53-Mediated Upregulation of BAX Gene Transcription Is Not Involved in Bax-α Protein Overexpression in the Left Ventricle of Spontaneously Hypertensive Rats

Cited by 23 publications

References 23 publications

Left ventricular remodeling with exercise in hypertension

Left ventricular remodeling with exercise in hypertension

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

Effect of AT1 receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension

Contact Info

Product

Resources

About

Effect of AT₁ receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension