Aldosterone stimulation mediates cardiac metabolism remodeling via Sirt1/AMPK signaling in canine model

Liu, Guangzhong; Zhang, Song; Li, Yanyan; Liu, Yongwu; Zhang, Yun; Zhao, Xinghui; Yuan, Yue; Zhang, Jiawei; Khannanova, Zulfiia; Li, Yue

doi:10.1007/s00210-019-01641-2

Cited by 11 publications

(4 citation statements)

References 41 publications

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“… 159 , 160 Beta-blockade is accompanied by up-regulation of AMPK, 161 , 162 and carvedilol up-regulates PGC-1α 163 and appears to enhance autophagic flux through SIRT1 stimulation 164 and by mTOR inhibition. 165 Spironolactone activates SIRT1/AMPK in the heart, 166 and its action to inhibit Akt/mTOR signalling has been linked to its effect to promote autophagic flux. 167 , 168 PGC-1α activation can interfere with the deleterious actions of mineralocorticoid receptor activation.…”

Section: Importance Of Longevity Gene Signalling and Autophagy Modulamentioning

confidence: 99%

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Packer

2020

European Heart Journal

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The two primary molecular regulators of lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). Each plays a central role in two highly interconnected pathways that modulate the balance between cellular growth and survival. The activation of SIRT1 [along with peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) and adenosine monophosphate-activated protein kinase (AMPK)] and the suppression of mTORC1 (along with its upstream regulator, Akt) act to prolong organismal longevity and retard cardiac ageing. Both activation of SIRT1/PGC-1α and inhibition of mTORC1 shifts the balance of cellular priorities so as to promote cardiomyocyte survival over growth, leading to cardioprotective effects in experimental models. These benefits may be related to direct actions to modulate oxidative stress, organellar function, proinflammatory pathways, and maladaptive hypertrophy. In addition, a primary shared benefit of both SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 inhibition is the enhancement of autophagy, a lysosome-dependent degradative pathway, which clears the cytosol of dysfunctional organelles and misfolded proteins that drive the ageing process by increasing oxidative and endoplasmic reticulum stress. Autophagy underlies the ability of SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 suppression to extend lifespan, mitigate cardiac ageing, alleviate cellular stress, and ameliorate the development and progression of cardiomyopathy; silencing of autophagy genes abolishes these benefits. Loss of SIRT1/PGC-1α/AMPK function or hyperactivation of Akt/mTORC1 is a consistent feature of experimental cardiomyopathy, and reversal of these abnormalities mitigates the development of heart failure. Interestingly, most treatments that have been shown to be clinically effective in the treatment of chronic heart failure with a reduced ejection fraction have been reported experimentally to exert favourable effects to activate SIRT1/PGC-1α/AMPK and/or suppress Akt/mTORC1, and thereby, to promote autophagic flux. Therefore, the impairment of autophagy resulting from derangements in longevity gene signalling is likely to represent a seminal event in the evolution and progression of cardiomyopathy.

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Section: Importance Of Longevity Gene Signalling and Autophagy Modulamentioning

confidence: 99%

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Packer

2020

European Heart Journal

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“…Pyroptosis was defined as a gasdermin-mediated proinflammatory programmed cell death process, which is different from apoptosis (a noninflammatory program of cell death) [44][45][46]. Some studies recently demonstrated that the pyroptosis in the aortic wall contributes to the development of AAA through promoting the chronic inflammatory manner [47,48].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of bulk RNA-seq and single-cell RNA-seq reveals the function of pyrocytosis in the pathogenesis of abdominal aortic aneurysm

Zhao,

Cang,

Liu

et al. 2023

Aging

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Pyrocytosis is involved in the development of abdominal aortic aneurysm (AAA), we explored the pyrocytosis-related hub genes in AAA and conducted a diagnostic model based on the pyrocytosis-related genes score (PRGs). A total of 2 bulk RNA-seq (GSE57691 and GSE47472) datasets and pyrocytosis-related genes were integrated to obtain 24 pyrocytosis-related different expression genes (DEGs). The LASSO Cox regression analysis was conducted to filter out 7 genes and further establish the nomogram signature based on the PRGs that exhibited a good diagnosis value. Weighted gene co-expression network analysis (WGCNA) established 14 gene modules and further identified 6 hub genes which were involved in the regulatory process of pyrocytosis in AAA. At the single cell level, we further identified 3 immune cells were highly associated with the pyrocytosis process in AAA. Finally, the cell-cell communication demonstrated that fibroblasts and endothelial cells and myeloid cells maintained close communications. Here, we identified the dysfunctional expressed pyrocytosis-related genes and immune cells in AAA, which provide a comprehensive understanding of the pathogenesis of AAA.

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“…Fresh atrial and proximal colon tissues were cut into 5-μm sections, xed in 4% paraformaldehyde and embedded with para n. Then, the tissues were stained with hematoxylin and eosin (HE), Masson's trichrome and TUNEL staining according to our previous study [22]. The HE staining was used to determine atrial and proximal colon structure.…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting procedures in the present study were essentially the same as described in a previous study [22]. Brie y, proteins were separated by electrophoresis on 8% to 12% SDS-polyacrylamide gels and transferred moist to polyvinylidene di uoride membranes.…”

Section: Methodsmentioning

confidence: 99%

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

Zhang¹,

Zhang²,

Luo³

et al. 2020

Preprint

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Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.

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Aldosterone stimulation mediates cardiac metabolism remodeling via Sirt1/AMPK signaling in canine model

Cited by 11 publications

References 41 publications

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Integrated analysis of bulk RNA-seq and single-cell RNA-seq reveals the function of pyrocytosis in the pathogenesis of abdominal aortic aneurysm

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

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