Reverse Remodeling of Cardiac Myocyte Hypertrophy in Hypertension and Failure by Targeting of the Renin-Angiotensin System

Tamura, Tetsutaro; Said, Suleman; Harris, Jason; Lu, Weida; Gerdes, A. Martin

doi:10.1161/01.cir.102.2.253

Cited by 94 publications

(49 citation statements)

References 37 publications

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“…Remodeling of the ventricle, clinically manifested as changes in size, shape, and function of the heart after cardiac injury, 26 is an important mechanism underlying the progression of heart failure. 27 It is a process that is common to multiple causes of heart failure 28,29 and that can be delayed or even reversed by appropriate treatment. 23 Eccentric remodeling in the control animals was suggested in the present study by a higher magnitude of ventricular and left atrial enlargement associated with thinning of the infarct-related posterior wall and the overall increase in heart weight.…”

Section: Discussionmentioning

confidence: 99%

Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction

et al. 2007

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Background-Myocardial infarction modifies the distribution of stress within the heart, increasing wall stress in ischemic and surrounding tissue, which often leads to adverse left ventricular remodeling. Electrical preexcitation pacing with appropriate timing of high-stress regions can reduce local strain and may attenuate global remodeling. Methods and Results-Myocardial infarction was induced in 24 swine to study the short-term (nϭ12) and long-term (nϭ12) effects of therapy. Sonomicrometry and hemodynamic measurements were used to show the mechanistic effects of preexcitation and to determine the optimal stimulation site and atrioventricular delay. Lagrangian strain was used to assess regional loading characteristics. Long-term study animals were randomized to 8 weeks of preexcitation (therapy) or no pacing (control). Echocardiograms were performed 2 days after myocardial infarction and repeated at 60 days, when tissue weights and apoptosis were assessed. Preexcitation reduced regional strain in the short term, with the best results achieved when the border region was paced at an atrioventricular delay of 50% of the intrinsic PR interval. In the long term, the changes in left ventricular internal diameter and left atrial size were decreased in therapy animals versus control animals (0.9Ϯ0.3 versus 1.5Ϯ0.5 cm, Pϭ0.03, and 1.06Ϯ0.78 versus 2.32Ϯ0.88 cm, PϽ0.04, respectively). Heart weight was significantly lower in the therapy animals than in the control animals (319.8Ϯ20.8 versus 359.6Ϯ29.3 g, Pϭ0.02). Although not significant, cardiomyocyte apoptosis trended lower in the therapy group. Conclusions-Preexcitation of the left ventricle after myocardial infarction reduced strain and stroke work in the infarct and border regions in the short term and attenuated adverse ventricular remodeling in the long term.

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Section: Discussionmentioning

confidence: 99%

Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction

et al. 2007

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“…Ang II induces apoptosis of endothelial cells 12 and enhances the proliferation of smooth muscle cells. 13 Experimental and clinical studies 14,15 show that Ang II plays a critical role in the remodeling of blood vessels and myocardium after acute myocardial infarction. The biological function of Ang II is mainly mediated by its type 1 (AT 1 ) and type 2 (AT 2 ) receptors.…”

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confidence: 99%

Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Chen²,

Mehta³

2001

Hypertension

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Abstract-Transforming growth factor-␤1 and its subtype receptor endoglin are key components in angiogenesis. We explored the role of angiotensin (Ang) II in the expression of endoglin and the underlying intracellular signaling mechanism in human coronary artery endothelial cells. Incubation of cells with Ang II upregulated endoglin expression in a concentration-and time-dependent manner (maximal effect with 10 Ϫ6 mol/L Ang II at 24 hours). The Ang II type 1 receptor blocker losartan, but not the type 2 receptor blocker PD 123,319, completely blocked the effect of Ang II. In parallel experiments, the mitogen-activated protein kinase inhibitor PD 098,059 fully inhibited the effect of Ang II on the expression of endoglin. Incubation of endothelial cells with Ang II also increased the expression of transforming growth factor-␤1 and -␤2 receptors and simultaneously decreased the levels of transforming growth factor-␤1. These effects of Ang II were also attenuated by losartan. We propose that Ang II via its type 1 receptor activation modulates the expression of transforming growth factor-␤1 receptors in human coronary endothelial cells. The activation of mitogen-activated protein kinase plays an important role in this process. These observations provide a new clue regarding the regulatory effect of Ang II on vascular remodeling after injury. (Hypertension. 2001;38:1062-1067.)

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“…Echocardiography was performed in each animal before it was euthanized using a Visualsonics 660 imaging system (20-MHz transducer; Toronto, Canada) as described previously (1,16). Briefly, rats were anesthetized using isoflurane (1.5%).…”

Section: Methodsmentioning

confidence: 99%

Changes in left ventricular function and remodeling after myocardial infarction in hypothyroid rats

Chen

Redetzke

Said

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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It has been shown that hypothyroidism may lead to delayed wound healing after experimental myocardial infarction (MI) in rats and increased infarct size in dogs. However, the long-term effect of hypothyroidism on left ventricular (LV) remodeling after MI has not been determined. Adult female Sprague-Dawley rats with and without surgical thyroidectomy (TX) were used in the study. Four weeks after TX, MI or sham MI was performed on TX and non-TX rats. Rats from all groups were examined 4 wk later. Four weeks after TX, hypothyroid-induced LV dysfunction was confirmed by echocardiography. In terminal experiments 4 wk after MI, TX sham-MI rats showed smaller hearts and impaired LV function compared with non-TX sham-MI controls. TX ϩ MI rats showed smaller hearts with bigger infarct areas, higher LV end-diastolic pressures, and greater impairment of relaxation (ϪdP/dt) compared with non-TX MI rats. Relative changes after MI between TX and non-TX rats for most other hemodynamic and echocardiographic indexes were similar. These results suggest that preexisting hypothyroidism exaggerates post-MI remodeling and worsens LV function, particularly diastolic function. low thyroid function; cardiac ischemia; heart failure HYPOTHYROIDISM IS A common condition in the general population. The prevalence rate is 4.6% in the United States population (0.3% clinical, 4.3% subclinical), is higher in females than in males, and increases with age (4). Hypothyroidism has been found to be associated with an increased risk of cardiovascular diseases such as atherosclerosis and myocardial infarction (MI) (3,19). Hypothyroidism has also been shown to delay wound healing in experimental MI rats (9) and causes increased MI size in dogs (7). However, the long-term effect of preexisting hypothyroidism on post-MI left ventricular (LV) remodeling is unknown.In this study, thyroidectomized (TX) rats were used to investigate the influence of hypothyroidism on LV remodeling after MI. We found that hypothyroid rats developed cardiac atrophy and had less LV chamber dilatation but more severe LV dysfunction 4 wk after MI. MATERIALS AND METHODSExperimental design. Adult female euthyroid (non-TX) and TX Sprague-Dawley rats weighing between 209 and 257 g were purchased from Charles River Laboratories (Wilmington, MA). MI surgery was performed 4 wk after TX. Animals from non-TX or TX groups were randomly assigned to MI or sham-MI surgery, respectively. MI was produced by a ligation of the left descending coronary artery as described in previous publications; sham MI was produced with a similar procedure, except the ligature was loosely tied (1, 15). Survivors were placed into the following groups: 1) TX ϩ MI (n ϭ 8), 2) TX ϩ sham-MI (n ϭ 10), 3) non-TX ϩ MI (MI, n ϭ 11), and 4) non-TX sham-MI group (S, n ϭ 10). Animals were housed two per cage and kept on a 12-h:12-h light-dark cycle with food and water provided ad libitum. Pre-MI surgery echocardiographic data were collected 4 wk after TX. In terminal experiments 4 wk later, cardiac function was assessed by...

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Reverse Remodeling of Cardiac Myocyte Hypertrophy in Hypertension and Failure by Targeting of the Renin-Angiotensin System

Cited by 94 publications

References 37 publications

Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction

Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction

Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Changes in left ventricular function and remodeling after myocardial infarction in hypothyroid rats

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