Pim Kinases: Important Regulators of Cardiovascular Disease

Nock, Sophie; Karim, Enamul; Unsworth, Amanda J.

doi:10.3390/ijms241411582

Cited by 6 publications

(3 citation statements)

References 148 publications

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“…The PIM kinase family plays a crucial role in the inflammatory process. Studies have shown that the three PIM family kinases also fulfil broader pathological functions in cardiovascular diseases, including in inflammation, thrombosis and cardiac injury ( Nock et al, 2023 ). In a transcriptomic study of inflammation in psoriasis, PIM3 kinase is located among key regulator transcripts ( Garshick et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Gaining new insights into the etiology of ulcerative colitis through a cross-tissue transcriptome-wide association study

Ren,

Sun,

Zhai

et al. 2024

Front. Genet.

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BackgroundGenome-wide association studies (GWASs) have identified 38 loci associated with ulcerative colitis (UC) susceptibility, but the risk genes and their biological mechanisms remained to be comprehensively elucidated.MethodsMulti-marker analysis of genomic annotation (MAGMA) software was used to annotate genes on GWAS summary statistics of UC from FinnGen database. Genetic analysis was performed to identify risk genes. Cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signatures (UTMOST) was performed to compare GWAS summary statistics with gene expression matrix (from Genotype-Tissue Expression Project) for data integration. Subsequently, we used FUSION software to select key genes from the individual tissues. Additionally, conditional and joint analysis was conducted to improve our understanding on UC. Fine-mapping of causal gene sets (FOCUS) software was employed to accurately locate risk genes. The results of the four genetic analyses (MAGMA, UTMOST, FUSION and FOCUS) were combined to obtain a set of UC risk genes. Finally, Mendelian randomization (MR) analysis and Bayesian colocalization analysis were conducted to determine the causal relationship between the risk genes and UC. To test the robustness of our findings, the same approaches were taken to verify the GWAS data of UC on IEU.ResultsMultiple correction tests screened PIM3 as a risk gene for UC. The results of Bayesian colocalization analysis showed that the posterior probability of hypothesis 4 was 0.997 and 0.954 in the validation dataset. MR was conducted using the inverse variance weighting method and two single nucleotide polymorphisms (SNPs, rs28645887 and rs62231924) were included in the analysis (p < 0.001, 95%CI: 1.45-1.89). In the validation dataset, MR result was p < 0.001, 95%CI: 1.19-1.72, indicating a clear causal relationship between PIM3 and UC.ConclusionOur study validated PIM3 as a key risk gene for UC and its expression level may be related to the risk of UC, providing a novel reference for further improving the current understanding on the genetic structure of UC.

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Section: Discussionmentioning

confidence: 99%

Gaining new insights into the etiology of ulcerative colitis through a cross-tissue transcriptome-wide association study

Ren,

Sun,

Zhai

et al. 2024

Front. Genet.

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“…Dr Alexander Brill (University of Birmingham, UK) kicked off this session by presenting new data on how hyperactivation of inflammasomes (NLRP3) in megakaryocyte linage induces anaemia and inflammation in mouse models. Dr Sophie Nock (Manchester Metropolitan University, UK) discussed how PIM kinases are novel regulators of platelet and megakaryocyte thromboxane A2 receptor (TPαR) and CXCR4 ( 20 ). New in vivo studies on Protein S and the TFPIα pathway were discussed by Dr Anastasis Petri (Imperial College London, UK) who described the role of Protein S in acting as a co-factor for human TFPIα and in controlling fibrin accumulation.…”

Section: Oral Communication Sessionsmentioning

confidence: 99%

Novel therapeutics and emerging technology in haemostasis and thrombosis: highlights from the British society for haemostasis and thrombosis annual meeting

Whyte,

Morrow,

Gauer

et al. 2023

Front. Cardiovasc. Med.

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“…PIM1 is mainly expressed in B lymphocyte and myeloid system, and overexpressed in hematopoietic malignancies and prostate cancer (from GENECARD). The PIM1 gene has been reported to not only exhibit widespread expression in various cardiovascular tissues, such as the heart, coronary artery, aorta, and blood, but also show high expression in cardiovascular diseases affected by numerous risk factors (Nock et al, 2023). Noteworthily, PIM1 has been underscored to promote inflammation (Yang & Chen, 2023).…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhetinic acid alleviates atrial fibrillation by inhibiting the expression of PIM1

Liang,

Zhang,

Zhao

et al. 2024

Chem Biol Drug Des

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Glycyrrhetinic acid (GA) is known to exert a cardioprotective effect, while its mechanism in atrial fibrillation (AF) remains poorly defined. Accordingly, isoprenaline (ISO) was applied to establish the rat AF model, and then GA (5, 10, and 20 mg/kg/day) was administrated to these rats for a total of 21 days. The fibrosis and pathological conditions of rat atrial tissues were observed. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was adopted to calculate the levels of proto‐oncogene serine/threonine‐protein kinase Pim1 (PIM1) and Interleukin (IL)‐4/6/13/17. For in‐vitro experiments, isolated cardiac fibroblasts received the transfection with PIM1‐specific overexpression plasmid or siPIM1 and the treatment with ISO. Subsequently, cell viability was gauged by cell counting kit‐8 assay. The protein levels of alpha‐smooth muscle actin (α‐SMA), collagen I and III, transforming growth factor‐beta1 (TGF‐β1) and mothers against decapentaplegic homolog 7 (Smad7) were measured by western blot. GA led to the shortened duration of AF and alleviated myocardial fibrosis and atrial tissue lesions in ISO‐treated AF rats in vivo. Meanwhile, GA inhibited the expressions of PIM1 and IL‐4/6/13/17 in the atrial tissue of AF model rats. In the meantime, enhanced cell viability, inhibited expressions of PIM1, IL‐4/6/13/17, α‐SMA, collagen‐I, collagen‐III and TGF‐β1, and promoted Smad7 expression were observable in ISO‐treated cardiac fibroblasts in vitro. Oppositely, the effects of GA were reversed following PIM1 overexpression, while knockdown of PIM1 enhanced the effects of GA on cardiac fibroblasts. Collectively speaking, GA alleviates AF through suppressing the expression of PIM1.

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Pim Kinases: Important Regulators of Cardiovascular Disease

Cited by 6 publications

References 148 publications

Gaining new insights into the etiology of ulcerative colitis through a cross-tissue transcriptome-wide association study

Gaining new insights into the etiology of ulcerative colitis through a cross-tissue transcriptome-wide association study

Novel therapeutics and emerging technology in haemostasis and thrombosis: highlights from the British society for haemostasis and thrombosis annual meeting

Glycyrrhetinic acid alleviates atrial fibrillation by inhibiting the expression of PIM1

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