The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies

Cai, Zhulan; Wu, Cencen; Xu, Yuan; Cai, Jiageng; Zhao, Mengmeng; Zu, Lingyun

doi:10.14336/ad.2022.0523

Cited by 17 publications

(11 citation statements)

References 140 publications

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“…The main consequence of reduced NO bioavailability in HFpEF is impaired signaling through the intracellular NO-cGMP-PKG pathway (Figure 3) [87]. NO diffusion into the underlying vascular smooth muscle cells leads to microvessel dilatation.…”

Section: Low No-cgmp-pkg Pathway Activity As a Major Contributor Of M...mentioning

confidence: 99%

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

Ovchinnikov,

Potekhina,

Arefieva

et al. 2024

IJMS

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Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

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Section: Low No-cgmp-pkg Pathway Activity As a Major Contributor Of M...mentioning

confidence: 99%

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

Ovchinnikov,

Potekhina,

Arefieva

et al. 2024

IJMS

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“…GO and KEGG annotation results demonstrated enrichment in pathways that regulate cell shape, axonogenesis, cell division site, caveola, transcription coactivator activity, and transmembrane transporter binding. VSM contractions and the cGMP-PKG signaling pathway are involved in the pathological mechanisms and potential treatments of heart failure (34).…”

Section: Go/kegg Analysesmentioning

confidence: 99%

Bioinformatics Analysis of Immune Cell Infiltration Patterns and Potential Diagnostic Markers in Atherosclerosis

Ji,

Yuan,

Jiang

et al. 2023

Preprint

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Background This study aimed to investigate efficient diagnostic markers and molecular mechanisms of atherosclerosis and to analyze the role of immune infiltration through bioinformatics analysis. Results Expression profile datasets (GSE28829 and GSE43292) of patients with atherosclerosis and healthy controls were downloaded from the GEO database. Glutamine (GLN) metabolism-associated genes were obtained from the Molecular Signatures Database (MSigDB). The limma package in R was used to identify differentially expressed genes (DEGs). Significant modules were filtered using Weighted Gene Co-expression Network Analysis (WGCNA). MSigDB sets were subjected to Gene Set Enrichment Analysis and Gene Set Variation Analysis. The biological functions of DEGs were examined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. STRING and Cytoscape software were used to identify hub genes and functional modules through protein–protein interaction (PPI) network analysis. The xCell software was adopted to assess the composition patterns of immune and stromal cells. Correlation analyses were performed for key genes and immune cell subtypes. We identified 308 DEGs and GLN-associated genes. Functional enrichment analysis showed that these genes were strongly enriched in muscle contract, muscle tissue development, cutile fiber, mycobacterial, and actin binding. Enriched KEGG pathways comprised dilated cardiomyopathy, Hypergraphic cardiomyopathy, and the cAMP signaling pathway. In the PPI network analysis, 27 genes were identified as hub genes. The area under the curve (AUC) values of 27 biomarkers were relatively high, indicating high diagnostic values. The atherosclerosis group exhibited a markedly higher degree of infiltration than the control group. Conclusions This study identified 27 GLN-associated genes as potential biomarkers for the diagnosis of atherosclerosis. It provides a new perspective on immune responses that facilitates exploration of the molecular mechanisms of atherosclerosis.

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“…HFpEF diastolic stiffness is influenced by the activities of the NO, cGMP, and PKG pathway, regardless of ejection fraction. 107 , 108 The NO–cGMP–PKG–titin pathway is anticipated to be a primary predictor of left ventricle (LV) diastolic stiffness in diabetic HFpEF patients given the findings of severe oxidative stress, vascular inflammation, endothelial dysfunction, and lower bioavailability of NO in cardiomyocytes of DCM patients. 109 , 110 Calcium–calmodulin-dependent protein kinase II, a Ca 2+ activated enzyme promotes cardiac adaptation by increasing energy generation, glucose absorption, SR Ca 2+ release/reuptake, sarcolemmal ion fluxes, and myocyte contraction/relaxation.…”

Section: Abnormal Metabolite Associated Toxicitymentioning

confidence: 99%

A comprehensive review of the novel therapeutic targets for the treatment of diabetic cardiomyopathy

Dhar,

Venkadakrishnan,

Roy

et al. 2023

Therapeutic Advances in Cardiovascular Disease

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Diabetic cardiomyopathy (DCM) is characterized by structural and functional abnormalities in the myocardium affecting people with diabetes. Treatment of DCM focuses on glucose control, blood pressure management, lipid-lowering, and lifestyle changes. Due to limited therapeutic options, DCM remains a significant cause of morbidity and mortality in patients with diabetes, thus emphasizing the need to develop new therapeutic strategies. Ongoing research is aimed at understanding the underlying molecular mechanism(s) involved in the development and progression of DCM, including oxidative stress, inflammation, and metabolic dysregulation. The goal is to develope innovative pharmaceutical therapeutics, offering significant improvements in the clinical management of DCM. Some of these approaches include the effective targeting of impaired insulin signaling, cardiac stiffness, glucotoxicity, lipotoxicity, inflammation, oxidative stress, cardiac hypertrophy, and fibrosis. This review focuses on the latest developments in understanding the underlying causes of DCM and the therapeutic landscape of DCM treatment.

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The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies

Cited by 17 publications

References 140 publications

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

Bioinformatics Analysis of Immune Cell Infiltration Patterns and Potential Diagnostic Markers in Atherosclerosis

A comprehensive review of the novel therapeutic targets for the treatment of diabetic cardiomyopathy

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