Experimental reduction of miR-92a mimics arterial aging

Hazra, Sugata; Henson, Grant D.; Morgan, R. Garrett; Breevoort, Sarah R.; Ives, Stephen J.; Richardson, Russell S.; Donato, Anthony J.; Lesniewski, Lisa A.

doi:10.1016/j.exger.2016.08.007

Cited by 23 publications

(12 citation statements)

References 21 publications

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“…miR-92a is reduced both in arteries of older adults and mouse model of vascular aging ( 80 ). miR-92a inhibition (through an antagomiR) in young mice showed a phenotype similar to the one typical of arterial aging via tumor necrosis factor α receptor 1 and collagen type 1 upregulation.…”

Section: Mirnas In Cardiovascular Agingmentioning

confidence: 99%

microRNA in Cardiovascular Aging and Age-Related Cardiovascular Diseases

Lucia

Komici²,

Borghetti

et al. 2017

Front. Med.

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Over the last decades, life expectancy has significantly increased although several chronic diseases persist in the population, with aging as the leading risk factor. Despite improvements in diagnosis and treatment, many elderlies suffer from cardiovascular problems that are much more frequent in an older, more fragile organism. In the long term, age-related cardiovascular diseases (CVDs) contribute to the decline of quality of life and ability to perform normal activities of daily living. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level in both physiological and pathological conditions. In this review, we will focus on the role of miRNAs in aging and age-related CVDs as heart failure, hypertension, atherosclerosis, atrial fibrillation, and diabetes mellitus. miRNAs are key regulators of complex biological mechanisms, representing an exciting potential therapeutic target in CVDs. Moreover, one major challenge in geriatric medicine is to find reliable biomarkers for diagnosis, prognosis, and prediction of the response to specific drugs. miRNAs represent a very promising tool due to their stability in the circulation and unique signature in CVDs. However, further studies are needed to investigate their translational potential in the real clinical practice.

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Section: Mirnas In Cardiovascular Agingmentioning

confidence: 99%

microRNA in Cardiovascular Aging and Age-Related Cardiovascular Diseases

Lucia

Komici²,

Borghetti

et al. 2017

Front. Med.

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“…On the other hand, a protective effect of miR-92a on vascular homeostasis was also reported. In older adults and old B6D2F1 mice (an established model of vascular aging), miR-92a expression is reduced which contributes to age-related endothelial dysfunction and increased large artery stiffness ( Hazra et al, 2016 ). In our present work, miR-92a-3p delivered by pEVs targets to PTEN, which then activates the Akt signaling and causes Col8a1 deposition at the intimal injury arteries.…”

Section: Discussionmentioning

confidence: 99%

Platelet-Derived Extracellular Vesicles Increase Col8a1 Secretion and Vascular Stiffness in Intimal Injury

Bao

et al. 2021

Front. Cell Dev. Biol.

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The arterial mechanical microenvironment, including stiffness, is a crucial pathophysiological feature of vascular remodeling, such as neointimal hyperplasia after carotid endarterectomy and balloon dilatation surgeries. In this study, we examined changes in neointimal stiffness in a Sprague-Dawley rat carotid artery intimal injury model and revealed that extracellular matrix (ECM) secretion and vascular stiffness were increased. Once the endothelial layer is damaged in vivo, activated platelets adhere to the intima and may secrete platelet-derived extracellular vesicles (pEVs) and communicate with vascular smooth muscle cells (VSMCs). In vitro, pEVs stimulated VSMCs to promote collagen secretion and cell adhesion. MRNA sequencing analysis of a carotid artery intimal injury model showed that ECM factors, including col8a1, col8a2, col12a1, and elastin, were upregulated. Subsequently, ingenuity pathway analysis (IPA) was used to examine the possible signaling pathways involved in the formation of ECM, of which the Akt pathway played a central role. In vitro, pEVs activated Akt signaling through the PIP3 pathway and induced the production of Col8a1. MicroRNA (miR) sequencing of pEVs released from activated platelets revealed that 14 of the top 30 miRs in pEVs targeted PTEN, which could promote the activation of the Akt pathway. Further research showed that the most abundant miR targeting PTEN was miR-92a-3p, which promoted Col8a1 expression. Interestingly, knockdown of Col8a1 expression in vivo abrogated the increase in carotid artery stiffness and simultaneously increased the degree of neointimal hyperplasia. Our results revealed that pEVs may deliver miR-92a-3p to VSMCs to induce the production and secretion of Col8a1 via the PTEN/PIP3/Akt pathway, subsequently increasing vascular stiffness. Therefore, pEVs and key molecules may be potential therapeutic targets for treating neointimal hyperplasia.

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“…In addition, circulating miR-181a-5p decreases with aging and correlates closely with vascular inflammation and immunity [ 64 , 65 ]. Similarly, miR-92a-3p plays a key role in regulation of vascular growth [ 66 ] and its serum levels increase with aging [ 67 ]. Given our limited sample size and the relatively narrow age range of our participants, we did not detect an age-related difference in miR-181a-5p or miR-92a-3p (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Circulating MiRNAs as biomarkers of gait speed responses to aerobic exercise training in obese older adults

Zhang

Brinkley

Liu

et al. 2017

Aging

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Gait speed is a useful predictor of adverse outcomes, including incident mobility disability and mortality in older adults. While aerobic exercise training (AEX) is generally an effective therapy to improve gait speed, individual responses are highly variable. Circulating microRNAs (miRNAs) may contribute to inter-individual changes in gait speed with AEX. We examined whether plasma miRNAs are associated with gait speed changes (dGaitSp) in 33 obese older adults (age: 69.3±3.6 years, BMI: 34.0±3.1 kg/m2, 85% white, 73% women) who performed treadmill walking, 4 days/week for 5 months. Gait speed (baseline: 1.02±0.19 m/s; range of response: −0.2 to 0.35 m/s) was assessed using a 400 meter-fast-paced walk test. Using Nanostring technology, 120 out of 800 miRNAs were found to be abundantly expressed in plasma and 4 of these were significantly changed after AEX: miR-376a-5p increased, while miR-16-5p, miR-27a-3p, and miR-28-3p all decreased. In addition, baseline miR-181a-5p levels (r=-0.40, p=0.02) and percent changes in miR-92a-3p (r=-0.44, p=0.009) associated negatively with dGaitSp. Linear regression combined baseline miR-181a-5p and miR-92a-3p levels showed even stronger associations with dGaitSp (r=-0.48, p=0.005). These results suggest that circulating miR-181a-5p and miR-92a-3p may predict and/or regulate AEX-induced gait speed changes in obese older adults.

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Experimental reduction of miR-92a mimics arterial aging

Cited by 23 publications

References 21 publications

microRNA in Cardiovascular Aging and Age-Related Cardiovascular Diseases

microRNA in Cardiovascular Aging and Age-Related Cardiovascular Diseases

Platelet-Derived Extracellular Vesicles Increase Col8a1 Secretion and Vascular Stiffness in Intimal Injury

Circulating MiRNAs as biomarkers of gait speed responses to aerobic exercise training in obese older adults

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