miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging

Zhan, Jiaxin; Qin, Shanshan; Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang

doi:10.18632/aging.101118

Cited by 21 publications

(30 citation statements)

References 29 publications

(30 reference statements)

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“…Our finding in HAECs that Tat induces endothelial senescence and increased expression of miR‐34a compliment and extend the results of Zhan et al. () who demonstrated increased miR‐34a expression in senescent endothelial cells from HIV‐1 Tat transgenic mice. Similar to miR‐34a, miR‐217 also induces endothelial senescence through inhibition of SIRT1 (Menghini et al.…”

Section: Discussionsupporting

confidence: 91%

“…underlying the proatherogenic vascular effects of gp120 and Tat (Wang et al 2015;Zhan et al 2016;Haser and Sumpio 2017). Future studies are needed to elucidate how these HIV-1 proteins differentially disrupt cellular miR expression patterns and, in turn, compromise target proteins that regulate endothelial cell viability and function.…”

Section: Discussionmentioning

confidence: 99%

Effects of HIV-1 gp120 and tat on endothelial cell sensescence and senescence-associated microRNAs

et al. 2018

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The aim of this study was to determine, in vitro, the effects of X4 and R5 HIV‐1 gp120 and Tat on: (1) endothelial cell senescence and (2) endothelial cell microRNA (miR) expression. Endothelial cells were treated with media without and with: R5 gp120 (100 ng/mL), X4 gp120 (100 ng/mL), or Tat (500 ng/mL) for 24 h and stained for senescence‐associated β‐galactosidase (SA‐β‐gal). Cell expression of miR‐34a, miR‐217, and miR‐146a was determined by RT‐PCR. X4 and R5 gp120 and Tat significantly increased (~100%) cellular senescence versus control. X4 gp120 significantly increased cell expression of miR‐34a (1.60 ± 0.04 fold) and miR‐217 (1.52 ± 0.18), but not miR‐146a (1.25 ± 0.32). R5 gp120 significantly increased miR‐34a (1.23 ± 0.07) and decreased miR‐146a (0.56 ± 0.07). Tat significantly increased miR‐34a (1.49 ± 0.16) and decreased miR‐146a (0.55 ± 0.23). R5 and Tat had no effect on miR‐217 (1.05 ± 0.13 and 1.06 ± 0.24; respectively). HIV‐1 gp120 (X4 and R5) and Tat promote endothelial cell senescence and dysregulation of senescence‐associated miRs.

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“…In the present study, we identified the adverse effects of NRTIs, the most common class of ART in HIV infection, on vascular growth and development. In addition to the endothelial injury in arteriosclerosis, as the major concern of ART treatment, recent studies have also demonstrated other side effects of ART, such as endothelial cell senescence, renal endothelial dysfunction, endothelial activation and effects on endothelial progenitor cells (Zhan et al, ; Zungsontiporn et al, ; Echeverria et al, ; Meneses et al, ). However, few studies have referred to the effect of ART on angiogenic capability of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Nucleoside/nucleotide reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signalling in endothelial cells

Song

Ding

et al. 2017

British Journal of Pharmacology

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“…Tat has also been shown to affect the expression of some miRNAs in neurons. For instance, Tat upregulates the expression of miR-34a, a miRNA that targets CREB (Zhang et al, 2012;Zhan et al, 2016). The upregulation of miR-34a leads to the promotion of neuronal dysfunction (Hu et al, 2017;Periyasamy et al, 2019).…”

Section: Mechanism Of Neurotoxicitymentioning

confidence: 99%

HIV-1 Tat: Role in Bystander Toxicity

Ajasin

Eugenin

2020

Front. Cell. Infect. Microbiol.

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HIV Tat protein is a critical protein that plays multiple roles in HIV pathogenesis. While its role as the transactivator of HIV transcription is well-established, other non-viral replication-associated functions have been described in several HIV-comorbidities even in the current antiretroviral therapy (ART) era. HIV Tat protein is produced and released into the extracellular space from cells with active HIV replication or from latently HIV-infected cells into neighboring uninfected cells even in the absence of active HIV replication and viral production due to effective ART. Neighboring uninfected and HIV-infected cells can take up the released Tat resulting in the upregulation of inflammatory genes and activation of pathways that leads to cytotoxicity observed in several comorbidities such as HIV associated neurocognitive disorder (HAND), HIV associated cardiovascular impairment, and accelerated aging. Thus, understanding how Tat modulates host and viral response is important in designing novel therapeutic approaches to target the chronic inflammatory effects of soluble viral proteins in HIV infection.

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“…Mir-34a up-regulation, the reciprocal decline of its target SIRT1, is the biomarker for aging in the brain and a good predictor of deterioration of the brain function. The miR-34a expression is significantly increased in HIV-infected vascular endothelial cells (ECs) [126] as well as in primary neuronal cultures and neuronal cell lines [127]. MiR-146a was also up-regulated in these cells.…”

Section: Micrornamentioning

confidence: 99%

Brain Aging in HIV-1 Infection

Santerre¹,

Sawaya²

2018

Advances in HIV and AIDS Control

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It has been shown that patients carrying HIV-1 accumulate damage to cells and tissues that are not directly infected by the virus itself (e.g., neurons). Importantly, these include changes known as HIV-Associated Neurodegenerative Disorder (HAND) leading to the loss of neuronal functions. HAND is an outstanding problem in the clinical management of HIV-1 patients because suppression of infectious virus by cART does not completely block neurodegenerative changes. Neuropsychological studies disclose cognitive alteration (such as loss of Spatial and Declarative Memory) in a substantial proportion of HIV-1 infected patients, and analysis of post-mortem brain tissues isolated from HIV-1 patients treated with cART show signs of neurodegeneration. In the absence of HIV-1 infection of neurons, several mechanisms have been proposed for HAND, including indirect inflammatory effects in the CNS and direct effects of viral proteins (e.g., gp120) shed from activated HIV-1-infected cells. The fact that these viral proteins enter the neurons through several pathways suggests the presence of many competing mechanisms that can contribute to HAND, each of which has its advocates. Their relative contributions to clinical disease in vivo remain to be sorted out, and this is an outstanding problem in HIV research. This chapter will shed some light on the mechanisms used by HIV-1 leading to memory impairments and premature brain aging.

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miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging

Cited by 21 publications

References 29 publications

Effects of HIV-1 gp120 and tat on endothelial cell sensescence and senescence-associated microRNAs

Nucleoside/nucleotide reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signalling in endothelial cells

HIV-1 Tat: Role in Bystander Toxicity

Brain Aging in HIV-1 Infection

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