The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets

Jiang, Bing; Zhou, Xuan; Yang, Tao; Wang, Linlin; Feng, Longfei; Wang, Zheng; Xu, Jin; Jing, Weiyao; Wang, Tao; Su, Haixiang; Yang, Guowei; Zhang, Zheng

doi:10.3389/fcvm.2023.1088575

Cited by 18 publications

(8 citation statements)

References 246 publications

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“…The other protein, interferon alpha 2, was positively associated with short-term PM 2.5 [115]. Proper functioning of adaptive autophagy processes is important for cardiovascular health and aging [265–267].…”

Section: Resultsmentioning

confidence: 99%

Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes

Casella,

Kiles,

Urquhart

et al. 2023

Preprint

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A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short-or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease, and highlight contemporary challenges and opportunities associated with such efforts.

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Section: Resultsmentioning

confidence: 99%

Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes

Casella,

Kiles,

Urquhart

et al. 2023

Preprint

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“…Among the common pathways, two belonged to lipid metabolic pathways "Biosynthesis of unsaturated fatty acid" and "Fatty acid metabolism". Autophagy can contribute to CVD by engaging in various crucial signaling pathways, such as PI3K/Akt/mTOR, IGF/EGF, AMPK/mTOR, MAPKs, p53, Nrf2/p62, Wnt/β-catenin, and NF-κB pathways 91 . Recent investigations have uncovered the intricate mechanisms that underlie the therapeutic impact of NRG-1/ErbB signaling in addressing heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…Among the common pathways, two belonged to lipid metabolic pathways "Biosynthesis of unsaturated fatty acid" and "Fatty acid metabolism". 91 . Recent investigations have uncovered the intricate mechanisms that underlie the therapeutic impact of NRG-1/ErbB signaling in addressing heart failure.…”

Section: Discussionmentioning

confidence: 99%

Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for EstablishingCaenorhabditis elegansas an Animal Model for Cardiovascular Diseases

Ray,

Priya,

Malik

et al. 2023

Preprint

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Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients andin vitroconditions. Animal models play a pivotal and indispensable role in cardiovascular disease (CVD) research.Caenorhabditis elegans, a nematode species, has emerged as a prominent experimental organism widely utilised in various biomedical research fields. However, the specific number of CVD-related genes and pathways within theC. elegansgenome remains undisclosed to date, limiting its in-depth utilisation for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans andC. elegansthrough a systematic bioinformatic approach.A total of 1113 genes inC. elegansorthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes inC. elegans, aPPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs:pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2,andaha-1 in C. elegans.Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans andC. eleganslinked with CVDs that include autophagy (animal), the ErbB signalling pathway, the FoxO signalling pathway, the MAPK signalling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present inC. elegans,supporting the use ofC. elegansas a prominent animal model organism for cardiovascular diseases.

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“…However, only physiological autophagy has a protective effect and maintains cardiac function. Overexpression or inhibition of autophagy can promote the development of cardiovascular diseases [20]. Inhibiting autophagy in the ischaemic heart aggravates cardiomyocyte apoptosis, thereby inducing the progression of myocardial infarction towards cardiac dysfunction [25].…”

Section: Discussionmentioning

confidence: 99%

Beta1-adrenergic receptor autoantibodies contributes to atrial remodeling by PTEN-mediated repression ofcardiomyocyte autophagy and aggravation of cardiomyocyte apoptosis

Yang,

Sun,

et al. 2023

Preprint

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Purpose β1 adrenergic receptor autoantibodies (β1-AAbs) can promote atrial electrical remodelling and structural remodelling, ultimately leading to the development of atrial fibrillation (AF). Phosphatase and tensin homologue (PTEN) has been confirmed to be involved in AF, but its role in β1-AAb-induced AF is unclear. This study aimed to investigate the involvement of PTEN in the occurrence and development of β1-AAb-induced AF and explore the potential mechanism underlying its effect. Methods A β1-AAb-induced AF rat model was established by active immunization. The first section was divided into 3 groups: the control group, β1-AAb group, and β1-AAb+bisoprolol group. The second section was divided into 3 groups: the control group, β1-AAb group, and β1-AAb+Oroxin B group. Serum levels of β1-AAb, atrial tissue levels of cyclic monophosphate (cAMP), atrial electrophysiological parameters, cardiac structure and function, mitochondrial structure, autophagy levels, cardiomyocyte apoptosis, and myocardial fibrosis were examined. Results The results showed that β1-AAb induced electro-anatomical remodelling of the atrium, inhibited autophagy and increased apoptosis in atrial tissue. Blocking β1-AR could partially offset these effects. β1-AAb decreased PTEN expression in the atrium. In addition, activating PTEN with a specific agonist (Oroxin B) could inhibit the AKT/mTOR and NF-κB signalling pathways, increase autophagy, reduce apoptosis, and significantly improve atrial remodelling. Conclusion β1-AAbs inhibit PTEN protein expression and activate downstream signalling mediators (AKT/mTOR and NF-κB), thereby inhibiting autophagy and increasing apoptosis, which are involved in atrial remodelling. Bisoprolol and PTEN agonists ameliorate these effects.

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The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets

Cited by 18 publications

References 246 publications

Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes

Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes

Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for EstablishingCaenorhabditis elegansas an Animal Model for Cardiovascular Diseases

Beta1-adrenergic receptor autoantibodies contributes to atrial remodeling by PTEN-mediated repression ofcardiomyocyte autophagy and aggravation of cardiomyocyte apoptosis

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