How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+pumps are crucial

Blaustein, Mordecai P.

doi:10.1152/ajpheart.00131.2017

Cited by 17 publications

(16 citation statements)

References 124 publications

(169 reference statements)

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“…This pathway finally permits the transcription of gene encoding for pro-fibrotic factors [ 45 ], promoting cardiac hypertrophy. Relevant evidences showed that a chronic activation of this complex protein-kinase cascade could finally lead to heart failure [ 46 ]. It was hypothesized that the molecular pathway that leads to organ hypertrophy in vivo was similar to the one described in cultured vascular cells [ 16 ].…”

Section: The Correlation Between Endogenous Ouabain and Organ Damamentioning

confidence: 99%

“…It was assessed that in Rostafuroxin-sensitive patients, there is a decline of systolic blood pressure of 14 mmHg after 4 weeks of treatment [ 65 ]. Nowadays, we do not have data about the effect of Rostafuroxin on the treatment of renal failure and the effects of hypertension on patients with end-stage renal disease, but this compound might have the effect of amelioration of the grade of hypertrophy and heart failure [ 46 ]. The pharmacological profile and the selective mechanism of action of Rostafuroxin make it the prototype of a compound devoid of the cardiovascular and hormonal side effects associated with digitalis and diuretic.…”

Section: The Correlation Between Endogenous Ouabain and Organ Damamentioning

confidence: 99%

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Endogenous Ouabain and Related Genes in the Translation from Hypertension to Renal Diseases

Simonini

Casanova

Citterio

et al. 2018

IJMS

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The endogenous ouabain (EO) is a steroid hormone secreted by the adrenal gland with cardio-tonic effects. In this article, we have reviewed and summarized the most recent reports about EO, particularly with regard to how it may interact with specific genetic backgrounds. We have focused our attention on the EO’s potential pathogenic role in several diseases, including renal failure, essential hypertension and heart failure. Notably, these reports have demonstrated that EO acts as a pro-hypertrophic and growth-promoting hormone, which might lead to a cardiac remodeling affecting cardiovascular functions and structures. In addition, a possible role of EO in the development of acute kidney injury has been hypothesized. During the last decays, many important improvements permitted a deeper understanding of EO’s metabolisms and functions, including the characteristics of its receptor and the effects of its activation. Such progresses indicated that EO has significant implications in the pathogenesis of many common diseases. The patho-physiological role of EO in the development of hypertension and other cardiac and renal complications have laid the basis for the development of a new selective compound that could selectively modulate the genetic and molecular mechanisms involved in EO’s action. It is evident that the knowledge of EO has incredibly increased; however, many important areas remain to be further investigated.

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Section: The Correlation Between Endogenous Ouabain and Organ Damamentioning

confidence: 99%

Section: The Correlation Between Endogenous Ouabain and Organ Damamentioning

confidence: 99%

Endogenous Ouabain and Related Genes in the Translation from Hypertension to Renal Diseases

Simonini

Casanova

Citterio

et al. 2018

IJMS

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“…Diverse studies reported an association between cardiac hypertrophy and the severity of OSA [22, 23]. In addition, it is important to address that RH may lead to cardiac hypertrophy [24].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Canonical Pathways Associated with Blood Pressure Response to Sleep Apnea Treatment: A Post Hoc Analysis

et al. 2021

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Background: Several studies have reported an association between microRNAs (miRNAs) and hypertension or cardiovascular disease (CVD). In a previous study performed on a group of 38 patients, we observed a cluster of 3 miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) that were functionally associated with the cardiovascular system that predicted a favorable blood pressure (BP) response to continuous positive airway pressure (CPAP) treatment in patients with resistant hypertension (RH) and obstructive sleep apnea (OSA) (HIPARCO score). However, little is known regarding the molecular mechanisms underlying this phenomenon. Objectives: The aim of the study was to perform a post hoc analysis to investigate the genes, functions, and pathways related to the previously found HIPARCO score miRNAs. Methods: We performed an enrichment analysis using Ingenuity pathway analysis. The genes potentially associated with the miRNAs were filtered based on their confidence level. Particularly for CVD, only the genes regulated by at least 2 of the miRNAs were studied. Results: We observed that the miRNAs studied regulate 200–249 molecules associated with several functions and diseases, including extracranial solid tumors and abdominal neoplasms, among others. The cardiac hypertrophy and NF-kB signaling pathways were identified as the cardiovascular pathways most influenced by these 3 miRNAs. Conclusions: The mechanisms by which CPAP treatment decreases the BP in OSA patients with RH could be related to the cardiac hypertrophy and NF-kB signaling pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients who do not respond to CPAP treatment.

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“…Considering these ndings, it is possible to observe the role of the studied miRNAs in the cardiovascular-related pathways that are also affected by OSA. In addition, it is important to address that RH may lead to cardiac hypertrophy (6). Thus, the studied miRNAs associated with a favorable response to CPAP treatment could be involved in the regulation of such adverse outcome in the long-term.…”

Section: Discussionmentioning

confidence: 99%

Gene networks and canonical pathways associated with a favorable blood pressure response after CPAP treatment: the HIPARCO score post hoc analysis

Zapater

Santamaria-Martos

Targa

et al. 2020

Preprint

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Background: Several studies report an association between microRNAs (miRNAs) and hypertension or cardiovascular disease. In a previous study, we observed a cluster of three miRNAs (miR-378a-3p, miR-100-5p, and miR-486-5p) functionally associated with the cardiovascular system that predicted a favorable blood pressure response to continuous positive airway pressure (CPAP) treatment in patients with resistant hypertension (RH) and obstructive sleep apnea (OSA) (HIPARCO score). However, little is known regarding the molecular mechanisms underlying this. Thus, the aim of the present study was to perform a post hoc analysis to investigate the genes, functions and pathways related to the previously found HIPARCO-score miRNAs. Methods: We performed an enrichment analysis using Ingenuity Pathway Analysis. The genes potentially associated with the miRNAs were filtered based on their confidence level. Particularly for cardiovascular disease, only the genes regulated by at least two of the miRNAs were studied. Results: We observed that the miRNAs studied regulate 200-249 molecules associated with several functions and diseases, including extracranial solid tumors and abdominal neoplasms, among others. The cardiac hypertrophy and NF-kB signaling pathways were identified as the cardiovascular pathways most influenced by these three miRNAs. Conclusions: Considering this, the mechanisms by which CPAP treatment decreases the blood pressure in OSA patients with RH could be related to these pathways. Further investigations will be necessary to confirm these findings, contributing to the elucidation of new therapeutic targets in patients that do not respond to CPAP treatment.

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How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na⁺pumps are crucial

Cited by 17 publications

References 124 publications

Endogenous Ouabain and Related Genes in the Translation from Hypertension to Renal Diseases

Endogenous Ouabain and Related Genes in the Translation from Hypertension to Renal Diseases

Canonical Pathways Associated with Blood Pressure Response to Sleep Apnea Treatment: A Post Hoc Analysis

Gene networks and canonical pathways associated with a favorable blood pressure response after CPAP treatment: the HIPARCO score post hoc analysis

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