Impact of miRNAs on cardiovascular aging

Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs known as microRNAs （miRNAs） have been shown to regulate gene expression, which contributes to many physiological and pathophysiological processes in humans. Increasing evidence suggests that changes in miRNA expression profiles contribute to cellular senescence, aging and aging-related diseases. However, only a few miRNAs whose functions have been elucidated have been associated with aging and/or aging-related diseases. This article reviews the currently available findings regarding the roles of aging-related miRNAs, with a focus on cardiac and cardiovascular aging.

Green Tea Polyphenols Prevent Early Vascular Aging Induced by High-Fat Diet via Promoting Autophagy in Young Adult Rats

Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect of GTP on high-fat diets(HFD)induced-early vascular aging.Methods Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP(200 mg/kg body weight)for 18 weeks.In vitro experiment,human umbilical vascular endothelial cells(HUVECs)were treated with palmitic acid(PA)and GTP.Results The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD.In addition,the vascular oxidative injury was suppressed following GTP treatment.Furthermore,GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1,and restored SIRT3 expression in the aorta of HFD rats.Consistently,in cultured HUVECs,GTP inhibited cell senescence indicated by SA-β-gal and promoted endothelial autophagy compared with the PA treatment group.The activity of SIRT3 was specifically inhibited by 3-TYP,and the protective effect of GTP was consequently abolished.Conclusion The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.

Research Progress on the Relationship between Vascular Aging and Hypertension

Vascular aging refers to the structural and functional changes of the arterial wall with age.Wscular aging plays an important role in elderly diseases,such as hypertension.Therefore,the relationship between vascular aging and hypertension has attracted extensive attention.This article mainly reviews the mechanism of vascular aging and its influence on hypertension,so as to provide new ideas and directions for the research and prevention of hypertension.

Atherosclerosis,Vascular Aging and Therapeutic Strategies

With the arrival of the era of global population aging, we strive for healthy aging and a healthy senior life rather than simple prolongation of the physical age. For the past 50 years, cardiovascular diseases （CVD） have been the most common cause of death among the elderly people globally. In China, there has been an exponential increase in the incidence of heart disease and stroke in the elderly population. Atherosclerosis is the pathological change in the coronary artery disease, stroke, and peripheral vascular disease. Despite the significant benefit demonstrated, control of classic risk factors alone, such as lifestyle change or drug therapy, was shown to have limitations in reducing the incidence of cardiovascular events. Vascular aging has been shown to be an important independent predictor of CVD events. Interventions targeting vascular aging have emerged as a new paradigm in conjunction with control of risk factors for the prevention of CVD. Vascular aging and atherosclerosis are two distinct pathological changes and difficult to distinguish clinically. Recent research with Chinese medicine （CM） has shown encouraging observations, linking the clinical benefit of delaying vascular aging and treating atherosclerosis. These results demonstrate great potential of CM in the prevention and treatment of CVD.

Delaying Vascular Aging with Chinese Medicine:Implications from An Overview of the p53 and miR-34s Family

p53 is an important target for studying vascular aging.However,as people gradually learned more about the miR-34s and the relationship between miR-34s and p53,new research idea emerged.This paper tries to elaborate the feature of p53,microRNA and miR-34s in-depth,analyze the regulatory action of miR-34s on p53,and offer some new prevention and treatment prospects about vascular aging in Chinese medicine.

Efficacy of Renshen Sanqi Chuanxiong formula for preventing vascular aging

OBJECTIVE:To evaluate the efficacy of Renshen Sanqi Chuanxiong formula(RSCF)for preventing vascular aging,and to investigate the possible molecular mechanism underlying the actions of RSCF.METHODS:Potentially active components and their relatively direct targets were identified by combining drug-likeness(DL)screening using a target identification process.Vascular aging-associated targets for RSCF were obtained by selecting common genes not only from potential targets but also from human vascular aging-associated genes.Cytoscape 3.2.1 software was employed to visualize the complex compound-target and target-function networks.Biological process and molecular function were assessed,and the Kyoto Encyclopedia of Genes and Genomes and pathway enrichment analyses were performed using Clue GO.Pathways directly associated with vascular aging were integrated into a"vascular aging-related"pathway.RESULTS:Altogether,122 potentially active components of RSCF were identified through DL screening,and their corresponding 692 direct targets were retrieved via target prediction and identification.We identified 49 vascular aging-associated targets for RSCF by overlapping the 692 potential targets with 146 human vascular aging-associated genes.The results from the compound-target network indicated that most components acted on common targets and displayed synergistic action,which showed that the magnifying effects of RSCF were based on these common targets.The target-function network revealed that each target was involved in multiple function modules,suggesting that RSCF was multi-functional during treatment of vascular aging.The results of the Clue GO analysis indicated that most of the targets were associated with the hypoxia-inducible factor 1(HIF-1)signaling pathway.The results from the pathway analysis also indicated that an integrative vascular aging-related pathway mainly included an angiogenesis regulation module,cell-survival module,and oxidative stress-resistance module.CONCLUSION:Our results suggested that many components act synergistically on common targets to delay vascular aging,and each target is involved in multiple functional modules.The Clue GO analysis indicated that most of the targets were connected to the HIF-1 signaling pathway,FOXO signaling pathway,and thyroid hormone signaling pathway.

HuR and post-transcriptional regulation in vascular aging

HuR(ELAV11(embryonic lethal,abnormal vision)-like 1),a ubiquitously expressed member of the ELAV-like RNA-binding protein family,has been shown to regulate the stability and translation of mRNAs that encode factors regulating cellular senescence,thereby impacting on aging.In this review,we discuss the current knowledge of HuR’s role in vascular cell senescence and vascular aging.

Critical roles of sirtuin 1 in vascular aging and abdominal aortic aneurysm

With the support by the National Natural Science Foundation of China and National Science and Technology Support Project,the research team led by Prof.Liu Depei(刘德培)at the State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,discovered critical roles of sirtuin 1(SIRT1)in the vascular smooth

Vascular wall microenvironment:Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner

Vascular calcification and vascular ageing are“silent”diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes,as well as in the ageing population.Melatonin(MT)has been shown to induce cardiovascular protection effects.However,the role of MT on vascular calcification and ageing has not been well-identified.In this study,the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells(ECs)and vascular smooth muscle cells(VSMCs)in vascular calcification and vascular ageing.Furthermore,we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs.The exosomes secreted from melatonin-treated ECs(MT-ECs-Exos)inhibited calcification and senescence of VSMCs.Mechanistically,miR-302d-5p was highly enriched in MT-ECs-Exos,while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence.Notably,Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence.Furthermore,we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N^(6)-methyladenosine(m^(6)A)-dependent manner.Interestingly,MT alleviated vascular calcification and ageing in 5/6-nephrectomy(5/6 NTP)mice,a chronic kidney disease(CKD)induced vascular calcification and vascular ageing mouse model.MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice.ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice.Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway,dependent on m^(6)A methylation.

Effect of Extracts from Radix Ginseng,Radix Notoginseng and Rhizoma Chuanxiong on Delaying Aging of Vascular Smooth Muscle Cells in Aged Rats

Objective： To observe the effect of extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chuanxiong （EXT） on delaying vascular smooth muscle cells （VSMCs） aging in aged rats. Methods： VSMCs were obtained by the modified tissue explants technique and were shown to be positive for smooth muscle α-actin （SM-α-actin） by immunohistochemistry staining. VSMCs obtained from the young rats were served as the young control group; VSMCs obtained from the old rats were treated with no drug （the old group）, with low dose extracts （20 mg/L, the EXT low-concentration group） and high dose extracts （40 mg/L, the EXT highconcentration group）, and with Probucal （106 mol/L, the Probucal group） as a positive control. All groups were cultured for 24 h in the medium with 10% serum for 24 h followed by another 24 h in the serum-free medium. At the end of the 48-h culture, the following analyses were performed including determination of senescenceassociated β-galactosidase （SA β-Gal） activity, flow cytometry analysis of cell cycle, real-time quantitative reverse transcription polymerase chain reaction （RT-PCR） analyses of p16, Cyclin D1, cyclin-dependent kinase 4 （CDK4） and retinoblastoma （Rb） mRNA expression, and Western blotting analyses of p16, cyclin D1, CDK4 and phosphoretinoblastoma （pRb） protein expressions. Results： （1） In comparison to the younger rats, VSMCs from aged rats had significantly more SA β-Gal positive cells （P〈0.01） and more cells in S phase （P〈0.05）. VSMCs from the all treated groups showed a significant decrease in both SA β-Gal positive cells （P〈0.05） and S phase （P〈0.05） compared to the old rats. （2） Compared with the young group, VSMCs in the old group had a significant decrease in p16 and Rb mRNA expression and a significant increase in Cyclin D1 and CDK4 mRNA expression. Compared with the old group, VSMCs in the treated groups had a significant increase in p16 and Rb mRNA expression and a significant decrease in Cyclin D1 and CDK4 mRNA expression （P〈0.05）. （3） Compared with the young group, VSMCs in the old group had a significant decrease in p16 protein expression and a significant increase in Cyclin D1, CDK4 and pRb protein expressions （P〈0.05）. Compared with the old group, VSMCs in the treated groups had a significant increase in p16 protein expression and a significant decrease in cyclinD1, CDK4 and pRb protein expressions （P〈0.05）. Conclusions： VSMCs obtained from old rats showed typical signs of cellular senescence and vascular aging. EXT had an effect on delaying senescence of VSMCs in vitro by altering the p16-cyclinD/CDK-Rb pathway.

Age-related pro-inflammatory and pro-angiogenic changes in human aqueous humor

AIM： To reveal age-related aqueous cytokine changes in human aqueous humor.METHODS： Aqueous humor was collected from 12 young children（3-6.5 years old） and 71 healthy adults（22-106 years old） with cataract but without other systemic or ocular disorders. Levels of 22 cytokines, chemokines and vascular endothelial growth factor（VEGF） were measured and analyzed.RESULTS： The following proteins showed significant increase from childhood to adult： interferon-gamma（IFN-γ）, interleukin（IL）-13, IL-6, IL-12（p70）, IL-10, CCL2, CCL3, CCL4, CXCL8, CXCL9, CXCL10, IFN-α2 and VEGF（all P〈0.05）. IFN-γ, IL-13, IL-12（p70）, IL-10, CCL3, CXCL9 and VEGF also showed moderate strength age-related increase in the adult group（r〉0.5）. The strength of correlation between aging and CCL4 were fair（r=0.398）. The concentrations of IL-2, IL-4, IL-5, IL-1β and TNF-α were low in both groups.CONCLUSION： From childhood to adult, the immunological milieu of the anterior chamber become more pro-inflammatory and pro-angiogenic. Such changes may represent the parainflammation state of the human eye.

Research progress of CTSL in cardiovascular system

Cathepsin L(CTSL) is a member of cysteine cathepsin and has endopeptidase activity. CTSL exists widely in various tissues and cells and participates in protein degradation, extracellular matrix remodeling, autophagy and other processes. With the deepening of research, it is found that CTSL is related to the occurrence of cardiovascular diseases. This article introduces the research progress of CTSL in atherosclerosis, coronary heart disease,intimal hyperplasia, dilated cardiomyopathy, abdominal aortic aneurysm, hypertension, vascular aging, in order to provide research direction for CTSL.

Endothelial Cell Senescence and Age-Related Vascular Diseases

Advanced age is an independent risk factor for ageing-related complex diseases, such as coronary artery disease, stroke, and hypertension, which are common but life threatening and related to the ageing-associated vascular dysfunction. On the other hand, patients with progeria syndromes suffer from serious atherosclerosis, suggesting that the impaired vascular functions may be critical to organismal ageing, or vice versa. However, it remains largely unknown how vascular cells, particularly endothelial cell, become senescent and how the senescence impairs the vascular functions and contributes to the age-related vascular diseases over time. Here, we review the recent progress on the characteristics of vascular ageing and endothelial cell senescence in vitro and in vivo, evaluate how genetic and envi- ronmental factors as well as autophagy and stem cell influence endothelial cell senescence and how the senescence contributes to the age- related vascular phenotypes, such as atherosclerosis and increased vascular stiffness, and explore the possibility whether we can delay the age-related vascular diseases through the control of vascular ageing.