Roles of exosomal miRNA in vascular aging

Du, Shuangshuang; Ling, Hao; Guo, Ziyuan; Cao, Qidong; Song, Chunli

doi:10.1016/j.phrs.2020.105278

Cited by 23 publications

(13 citation statements)

References 151 publications

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“…miRNAs are potential biomarkers indicative of disease and health status and responsiveness to therapeutic interventions 38 – 43 . Findings from our study indicate that 14 circulating miRNAs are potential biomarkers of disease progression and lesion number, predicting the burden of CIA atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

Karere

Glenn

et al. 2023

Sci Rep

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Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, -451a, -191-5p, -148a-3p, -17-5p, -378c, and -144-3p) were differentially expressed between paired fatty streak lesion and no-lesion sites of the tissue, and 27 miRNAs (e.g., miR-92a-3p, -5001, -342-3p, miR-28-3p, -21-5p, -221-3p, 146a-5p, and -16-5p) in fibrous plaques. The expression of 14 blood miRNAs significantly correlated with extent of lesions and the number of plaques. We identified coordinately regulated miRNA-gene networks in which miR-17-5p and miR-146a-5p are central hubs and miR-5001 and miR-7975 are potentially novel miRNAs associated with early atherosclerosis. In summary, we have identified miRNAs expressed in lesions and in blood that correlate with lesion burden and are potential therapeutic targets and biomarkers. These findings are a first step in elucidating miRNA regulated molecular mechanisms that underlie early atherosclerosis in a baboon model, enabling translation of our findings to humans.

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Section: Discussionmentioning

confidence: 99%

Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

Karere

Glenn

et al. 2023

Sci Rep

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“…TGF-β1 can modulate normal and pathological cell differentiation and proliferation in an auto- or paracrine manner [ 58 ]. In particular, the ability of TGF-β signaling to activate target genes enables the pathway to impact diverse cellular processes including proliferation, differentiation, migration, apoptosis, and endothelial cell remodeling [ 59 , 60 ] with different and sometimes opposite effects on cancer cells. Actually, TGF-β normally exerts tumor-suppressive effects.…”

Section: Discussionmentioning

confidence: 99%

TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer

Scola

Bongiorno

Forte

et al. 2022

Genes

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Differential genetically determined expression of transforming growth factor-β (TGF-β pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular “milieu” involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-A rs3025039T was associated with an increased risk. To evaluate the effect of genotype combinations on NMSC susceptibility, we determined the frequencies of 31 pseudo-haplotypes due to non-random linkage among alleles of loci not lying on the same chromosome. Two pseudo-haplotypes that imply a minor allele of TGF-βR2 or minor allele of VEGF-A SNPs combined with major alleles of the other SNPs were, respectively, associated with a protective effect, and susceptibility to NMSC. In addition, a pseudo-haplotype involving minor alleles of TGF-β2 rs900, TGF-βR1 rs334348 and rs4522809 SNPs might be a susceptibility marker for NMSC. In conclusion, our data suggest that a complex interplay among the genetic polymorphisms of TGF-β, TGF-β receptors and VEGF-A genes might influence the net effect of genetic background of the patients on NMSC development. This might be relevant in the risk evaluation, diagnosis and treatment of NMSC.

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“…The importance is however confirmed by the lethality of deletion of Dicer and Drosha, the critical miRNA biogenesis factors (Bernstein et al, 2003;Chong et al, 2010). The level of individual miRNA or total spectrum of miRNA in sEV in a particular cell type very often is modified in development and ageing as well as in different pathologies and physiological or pharmacological treatments in vivo (Xia et al, 2019;Du et al, 2020). The study of particular miRNA and their role is typically done via two approaches, overexpression/delivery or downregulation/ silencing of discrete miRNA.…”

Section: Retinal Ganglion Cellsmentioning

confidence: 99%

The role of miRNA in retinal ganglion cell health and disease

Mead

Tomarev²

2022

Neural Regen Res

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miRNA are short non-coding RNA responsible for the knockdown of proteins through their targeting and silencing of complimentary mRNA sequences. The miRNA landscape of a cell thus affects the levels of its proteins and has significant consequences to its health. Deviations in this miRNA landscape have been implicated in a variety of neurodegenerative diseases and have also garnered interest as targets for treatment. Retinal ganglion cells are the sole projection neuron of the retina with their axons making up the optic nerve. They are a focus of study not only for their importance in vision and the myriad of blinding diseases characterized by their dysfunction and loss, but also as a model of other central nervous system diseases such as spinal cord injury and traumatic brain injury. This review summarizes current knowledge on the role of miRNA in retinal ganglion cell function, highlighting how perturbations can result in disease, and how modulating their abundance may provide a novel avenue of therapeutic research.

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Roles of exosomal miRNA in vascular aging

Cited by 23 publications

References 151 publications

Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer

The role of miRNA in retinal ganglion cell health and disease

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