(Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction

Ellmers, Leigh J.; Rademaker, Miriam T.; Charles, Christopher J.; Yandle, Tim G.; Richards, A. Mark

doi:10.1016/j.cardfail.2015.08.341

Cited by 20 publications

(17 citation statements)

References 41 publications

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“…The generation of the CSE −/− mice has been previously described [27]. The MI was induced as described previously [34][35][36]. In brief, a left lateral thoracotomy was performed under anesthesia induced by a single subcutaneous (SC) injection of 75 mg/kg ketamine (Ceva Ketamine, Ceva Animal Health Pty Ltd., Glenorie, NSW, Australia) and 1 mg/kg medetomidine hydrochloride (Domitor, Zoetis New Zealand Ltd., Auckland, NZ), with ventilation at 107 breaths/min; 1.5 mL tidal volume [34].…”

Section: Myocardial Infarctionmentioning

confidence: 99%

“…This dose regimen has been shown in rats to increase plasma H 2 S levels 2.8-fold [3]. The treatment period was chosen as the time required to observe significant hypertrophic and fibrotic changes post-MI in this model, reflecting long-term remodeling rather than the immediate response to injury [34][35][36].…”

Section: Treatment Protocolmentioning

confidence: 99%

“…Cardiac function was measured at 28 days by transthoracic echocardiography using an iE33 ultrasound machine (Philips Ultrasound, Bothell, WA, USA) with a 15-MHz linear transducer, as described previously [35,36]. The mice were placed in a shallow left lateral position under light inhalation anesthesia with 3.5% isofluorane (with a flow rate of 270 mL/min of oxygen) and maintained with 1.8% isofluorane (with a flow rate of 270 mL/min of oxygen) via nose cone.…”

Section: Echocardiographymentioning

confidence: 99%

“…A 2-dimensional (2D) image obtained in the parasternal short axis view at the level close to the papillary muscles, and a 2D M-mode trace recorded across the anterior and posterior wall of the left ventricle. Indices reported here are fractional shortening (FS) and left ventricular ejection fraction (LVEF) [35,36]. Mean arterial blood pressure (MAP) was measured at the same time by a noninvasive computerized tail cuff system (ADInstruments, Dunedin, NZ).…”

Section: Echocardiographymentioning

confidence: 99%

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Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

Ellmers

Templeton

Pilbrow

et al. 2020

IJMS

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Hydrogen sulfide (H2S) is recognized as an endogenous gaseous signaling molecule generated by cystathionine γ-lyase (CSE) in cardiovascular tissues. H2S up-regulation has been shown to reduce ischemic injury, and H2S donors are cardioprotective in rodent models when administered concurrent with myocardial ischemia. We evaluated the potential utility of H2S therapy in ameliorating cardiac remodeling with administration delayed until 2 h post-infarction in mice with or without cystathionine γ-lyase gene deletion (CSE−/−). The slow-release H2S donor, GYY4137, was administered from 2 h after surgery and daily for 28 days following myocardial infarction (MI) induced by coronary artery ligation, comparing responses in CSE−/− with wild-type (WT) mice (n = 5–10/group/genotype). Measures of cardiac function and expression of key genes associated with cardiac hypertrophy, fibrosis, and apoptosis were documented in atria, ventricle, and kidney tissues. Post-MI GYY4137 administration reduced infarct area and restored cardiac function, accompanied by reduction of the elevated ventricular expression of genes mediating cardiac remodeling to near-normal levels. Few differences between WT and CSE−/− mice were observed, except CSE−/− mice had higher blood pressures, and higher atrial Mir21a expression across all treatment groups. These findings suggest endogenous CSE gene deletion does not substantially exacerbate the long-term response to MI. Moreover, the H2S donor GYY4137 administered after onset of MI preserves cardiac function and protects against adverse cardiac remodeling in both WT and CSE-deficient mice.

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Section: Myocardial Infarctionmentioning

confidence: 99%

Section: Treatment Protocolmentioning

confidence: 99%

Section: Echocardiographymentioning

confidence: 99%

Section: Echocardiographymentioning

confidence: 99%

See 2 more Smart Citations

Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

Ellmers

Templeton

Pilbrow

et al. 2020

IJMS

Self Cite

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“…RAAS may be involved in a variety of pathogenic processes including induction of inflammation and adverse vascular remodelling, 102) stimulation of vascular oxidative stress, 103) establishment of peripheral insulin resistance 101) 103) and involvement in cardiac remodelling. 104) Recent evidence suggests that WAT-specific mineralocorticoid receptor (MR) activation is associated with direct detrimental effects on WAT in terms of insulin sensitivity and expansion, and it impairs endothelial function via a presumed paracrine effect of PVAT on the vascular wall. 105) Interestingly, MR inhibition reversed these effects.…”

Section: Crosstalk Between Wat and The Cardiovascular Systemmentioning

confidence: 99%

Exploring the Crosstalk between Adipose Tissue and the Cardiovascular System

2017

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Obesity is a clinical entity critically involved in the development and progression of cardiovascular disease (CVD), which is characterised by variable expansion of adipose tissue (AT) mass across the body as well as by phenotypic alterations in AT. AT is able to secrete a diverse spectrum of biologically active substances called adipocytokines, which reach the cardiovascular system via both endocrine and paracrine routes, potentially regulating a variety of physiological and pathophysiological responses in the vasculature and heart. Such responses include regulation of inflammation and oxidative stress as well as cell proliferation, migration and hypertrophy. Furthermore, clinical observations such as the “obesity paradox,” namely the fact that moderately obese patients with CVD have favourable clinical outcome, strongly indicate that the biological “quality” of AT may be far more crucial than its overall mass in the regulation of CVD pathogenesis. In this work, we describe the anatomical and biological diversity of AT in health and metabolic disease; we next explore its association with CVD and, importantly, novel evidence for its dynamic crosstalk with the cardiovascular system, which could regulate CVD pathogenesis.

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(Pro)renin Receptor Blockade Ameliorates Heart Failure Caused by Chronic Kidney Disease

Yoshida

Kanamori

Naruse

et al. 2019

Journal of Cardiac Failure

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(Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction

Cited by 20 publications

References 41 publications

Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

Exploring the Crosstalk between Adipose Tissue and the Cardiovascular System

(Pro)renin Receptor Blockade Ameliorates Heart Failure Caused by Chronic Kidney Disease

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