Progress of clinical evaluation for vascular aging in humans
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Yumin Qiu
Abstract
Human society is experiencing a serious aging process. Age-related arteriosclerotic cardiovascular diseases (ASCVD) are the most common cause of deaths around the world and bring a huge burden on the whole society. Vascular aging-related pathological alterations of the vasculature play an important role in the pathogenesis of ASCVD and morbidity and mortality of older adults. In this review, we describe the progress of clinical evaluation of vascular aging in humans, including functional evaluation, structural assessment, and cellular molecular markers. The significance of detection for vascular aging is highlighted, and we call for close attention to the evaluation for a better quality of life in the elderly population.
Introduction
The famous 17th-century physician Thomas Sydenham, recognized as “English Hippocrates” and the author of Observationes Medicae, observed, “a man is as old as his arteries”. Indeed, the world is stepping into an aging society. Aging is a major risk factor for the occurrence of arteriosclerotic cardiovascular diseases (ASCVD), which are the leading causes of long-term disability and mortality among the elderly around the world.[1] Importantly, advanced aging is the single most essential risk factor that dwarfs the effect conventional risk factors (e.g., hypertension, hyperglycemia, hypercholesterolemia),[1] and age-related ASCVD account for nearly half of all deaths worldwide (World Health Organization), consequently, addressing the value of clinical evaluation of age-related vascular diseases is considerably meaningful. Vascular aging causes multifaceted structural and functional vessels’ impairment, which shows the deleterious impact on cellular metabolism and function, and thus leads to the pathogenesis of ASCVD.[2] Thus, for better amelioration of unsuccessful vascular aging and prevention of age-related vascular pathologies, it is critical to identify vascular aging and dysfunction from multiple perspectives as to prevent the occurrence and development of vascular disease associated with old age (Table 1).
Clinical evaluation for vascular aging in humans
| Clinical evaluation | Methods | Description |
|---|---|---|
| Functional evaluation | FMD | FMD, carried out noninvasively with ultrasonography on the brachial artery, is a commonly used method for the evaluation of endothelial dysfunction. FMD provides a non-invasive, cheap, and repeatable measure of endothelial function and has been widely used in pathophysiological studies and management of aging vessels. |
| baPWV | baPWV has been reported as an index of arterial stiffness and serves as an indicator of cardiovascular risk and the severity of vascular aging-related damage. | |
| Endo-Pat | Endo-PAT, a safe, accurate, and non-invasive diagnostic device, is used for evaluating both small and large arteries to detect the status of vascular function and earliest stages of cardiovascular diseases. | |
| Infrared thermal imaging technology | Infrared thermal imaging technology is a method to improve visibility of participants in a dark environment by detecting their infrared radiation, in order to reflect the microcirculation and reveal the vascular function. | |
| Structural assessment | MRI | MRI is a non-invasive imaging method, which provides high spatial resolution for the morphological and compositional evaluation of the vessel wall and is a promising modality for assessment of vascular aging. |
| IMT | Carotid intima–media thickness is a surrogate measure of aging associated with cardiovascular risk factors and with cardiovascular outcomes, for detection of early stages of atherosclerosis and evaluation of arterial wall structure. | |
| CTA | CTA is a vascular imaging technique that can be carried out rapidly and safely for the evaluation of aging-related artery disease as well as other vascular applications. | |
| OCTA | OCTA has emerged as a fast, safe, and noninvasive procedure to provide depth-resolved images of blood flow in the retina and assess the retinal microvasculature, which is essential for the early detection of age-related chronic diseases, especially diabetes and hypertension. | |
| Cellular molecular markers | EPCs | EPCs are bone marrow-derived endothelial precursor cells and participate in the endothelial repair and endothelial function regulation, which is a surrogate biologic measure of vascular function and human age. |
| EMPs | EMPs are microparticles that are detached from the cell membrane of endothelial cells. The increasing level of EMPs is associated with the prognosis of age-related diseases. | |
| Sirtuins | Sirtuins, a class of NAD+-dependent deacetylases, are implicated in numerous biological pathways and are considered as an index of aging and a promising target for treating human diseases. | |
| Telomere and telomerase | Telomeres and telomerase are important in maintaining the chromosomal stability and integrity. The length of the shortest telomere is a key biomarker of the onset of aging. | |
| Mitochondria and superoxide flashes | Superoxide flashes are brief bursts of superoxide production within the matrix of single mitochondria and exhibit all-or-none properties. It has emerged as a relatively early and pivotal event of cell metabolism, differentiation, the stress response, and aging. | |
| Nucleolus | Maintenance of nucleolar homeostasis is demonstrated to contribute to counteracting cells’ aging because of the stability of DNA synthesis. | |
| cfDNA | cfDNA, all non-encapsulated DNA in the blood stream, can be recognized as a new biomarker of aging according to recent studies. | |
| Humanin | Humanin is an innovative 24-amino acid mitochondrial-derived peptide that has demonstrated cytoprotective effects. Humanin decreases with age in several species, including humans. | |
| Ageotype | Ageotypes may provide a molecular assessment of aging and reflect lifestyle and medical history, in order for better intervening in the vascular aging process. |
FMD: flow-mediated dilation; baPWV: brachial ankle pulse wave velocity; MRI: magnetic resonance imaging; IMT: intima-media thickness; CTA: computed tomographic angiography; OCTA: optical coherence tomography angiography; EPCs: endothelial progenitor cells; EMPs: endothelial microparticles; cfDNA: cell-free DNA
Functional evaluation of vascular aging
Vascular endothelial dysfunction is the initial process of vascular aging-related ASCVD. Detection for vascular function is of great significance to identify the vascular risk and prevent the pathogenesis of vascular-related ASCVD. In recent years, with the continuous development of vascular function research and the update of technology, noninvasive function detection indicators reflecting vascular aging have gradually been used in clinical and scientific research. At present, a large number of studies have confirmed that early detection of flow-mediated dilation (FMD),[3] brachial ankle pulse wave velocity (baPWV)[4] and ankle brachial index (ABI)[5] are important strategies to slow down vascular aging. In addition, more and more new technologies have been applied to the detection of vascular function.[6]
FMD and baPWV
FMD is the method describing the vascular vasodilation caused by the increase of lumen blood flow and shear stress. FMD decreased in patients with elevated blood pressure, and endothelial function assessed by FMD was impaired regardless of the blood pressure level of hypertensive patients after antihypertensive drug treatment[3]. At the same time, FMD is also an important assessment method of target organ injury.[7]
baPWV is another main index to detect the degree of arteriosclerosis, and its change is the overall reflection of abnormal structure and function of arteries. The results showed that baPWV was an independent predictor of hypertension, and the risk ratio of baPWV increased by 1 m/s was 1.10.[8] Based on the traditional cardiovascular risk factors, measuring baPWV can improve the effectiveness of predicting the development risk of ASCVD.[9]
Endo-Pat
Endo-Pat is based on a set of plethysmography biosensor system, which is used to measure the endothelium vasodilation and contraction function after reactive hyperemia at fingertips, and the result is presented as reactive hyperemia index (RHI). The study found that the sensitivity and specificity of 1.67 as a critical value of RHI for the diagnosis of endothelial dysfunction were 82% and 77%, respectively.[10] Endo-Pat is of great significance for screening of high-risk population and has gradually been set as a clinical function evaluation indicator of vascular aging.[11, 12]
Infrared thermal imaging technology
Infrared thermography, based on the principle of remote temperature measurement, records the infrared radiation wavelength emitted by human skin (affected by skin vascular relaxation and contraction factors) to analyze the multiple information of body surface temperature, and displays it in the form of thermal map, so as to reflect the microcirculation, the blood circulation of the lesion site, etc.[13] The study found that infrared thermal imaging technology has unique value in screening large population, detecting vascular function of chronic diseases such as hypertension, diabetes, and theirs complications.[14,15,16]
Structural assessment of vascular aging
The integrity of vascular structure is an important guarantee for the normal function of blood vessels, and it is also the key factor to maintain vascular health and delay vascular aging. At present, vascular structure evaluation indicators are gradually applied to clinical practice, including magnetic resonance imaging (MRI), carotid intima-media thickness (IMT), computed tomographic angiography (CTA), etc.
MRI
In the case of endothelial dysfunction and structural dysfunction, vascular hyperemia becomes blunted and can be measured noninvasively by a variety of quantitative MRI methods, including a blood oxygenation-level-dependent (BOLD) signal that reflects the combined effect of blood flow and capillary bed oxygen content, arterial spin labeling (ASL) for quantification of regional perfusion, phase contrast (PC) to quantify arterial flow waveforms, macrovascular blood flow velocity and rate, etc.[17] In the development of vascular aging, BOLD MRI can also be observed even in the absence of obvious ASCVD.[18, 19] Some studies have also found that there is an association between ASL-based measurement and the occurrence and severity of peripheral vascular disease.[20,21] In addition, based on the baseline characteristics of PC and arterial blood flow waveform, endothelial structure and function, vascular reactivity and blood flow reserve can be deeply understood.[22] MRI can also be used to quantify the cross-sectional area of blood vessels and to evaluate the structure of vascular wall or hemodynamics.[23]
IMT
Carotid IMT refers to the distance between the lumen surface of carotid intima and the interface of adventitia. IMT increases linearly with age and is considered as an independent risk factor for cardiovascular events.[24,25] At present, the international reference values recommended according to different ages are as follows: 40–49 years, <0.7 mm; 50–59 years, <0.8 mm; and 60 years or older, <0.9 mm.[26] Early identification and intervention of IMT plays an important role in delaying vascular aging and preventing subclinical development of atherosclerotic vascular disease.[27]
CTA
As a common clinical technique, CTA exerts essential role in the diagnosis of vascular structure variation and diseases. Recent studies found many novel noninvasive technologies such as CT-derived fractional flow reserve (FFR) for estimating the blood flow distribution and predicting the functional outcome after coronary stenting.[28,29] Other research showed that CTA may identify coronary arterial abnormalities and add information on coronary artery lesions in patients with Takayasu arteritis (TA), which acknowledges CTA as a useful technique in figuring out the pathological changes in the vessels.[30]
Optical coherence tomography angiography (OCTA)
Retinopathy caused by age-related diseases, especially diabetes mellitus and hypertension, is a serious neurovascular complication, which is a primary reason of blindness in the aging population.[31] OCTA is a promising and emerging technique for imaging the retinal vasculature without dye injection, and it appears as a comprehensive management of retinopathy related to vascular aging.[32] OCTA visualizes the ocular blood flow in the retinal network and is essential for locating and measuring the sizes of various pathological alternations. Studies have demonstrated that OCTA shows a favorable effect on detecting angiographic features, even before the disease onset, which may be a useful method for vascular aging-related diseases.[33]
Cellular molecular markers of vascular aging
At present, there is a lack of a universal marker for the detection of vascular aging. As the molecules expressed by senescent cells will change with the different cell types, senescence stimulation, and stimulation time, the phenotype and molecular markers of cell senescence still need to be further studied.
Endothelial progenitor cells (EPCs) and endothelial microparticles (EMPs)
EPCs are bone marrow-derived endothelial precursor cells that are present in peripheral blood. They can be directed to the vascular injury site and differentiate into mature endothelial cells, which is recognized as a landmark of the capacity of vascular repair. Studies found that circulating EPCs deficiency contributes to reduced arterial elasticity in persons of advancing age,[34] and impaired EPCs activity is associated with impaired vascular function.[35,36] These results demonstrated that the decrease in circulating EPCs number and activity may serve as a surrogate biologic measure of vascular function and human age.
EMPs are microparticles that are detached from the cell membrane of endothelial cells during activation, metabolism, apoptosis, and other cellular process. Elevations of EMPs in the circulation, mostly defined as CD31+/CD42+ microparticles, as well as alterations in their phenotype, were found in various pathological conditions related to endothelial dysfunction.[37] In addition, EMPs increase along with aging and vascular damage and emerged as the sensitive marker of endothelial perturbation in response to adverse stimuli.[38] Therefore, increasing level of EMPs is associated with prognosis of ASCVD, suggesting vascular aging.
Sirtuins
Sirtuins are a class of NAD+-dependent deacetylases. Anti-aging properties of sirtuins were first observed in 1999, for its overexpression was demonstrated to increase yeast lifespan by 70%.[39] Growing evidence has shown that sirtuins are essential for vascular aging through repair DNA damage, lowering oxidative stress, and alleviating inflammation.[40] For instance, SIRT1 is one of the most extensively studied proteins because of its capability of delaying vascular aging and preventing age-related diseases by catalyzing protein deacetylation and regulation of a series of transcription factors and coactivators, such as the forkhead box O (FOXO), nuclear factor-kappa B (NF-kB), and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α).[41] Besides, SIRT3 and SIRT5, two major NAD+-dependent deacetylases located in mitochondria that deacetylases mitochondrial proteins at their lysine residues, are confirmed to be beneficial for improving vascular functions via maintaining the balance of oxidative stress and augmenting the capacity of angiogenensis.[42, 43] Except for these, SIRT2, SIRT4, SIRT6, and SIRT7 also play an important role in regulating endothelial cell senescence.[39] Taken together, sirtuins, have multifaceted roles in the vascular function, are crucial for the maintenance of vascular homeostasis, and are acknowledged as a novel biomarker of vascular aging.
Telomere and telomerase
It is well established that the length of the shortest telomere is a key biomarker of the onset of aging. There is an increasing number of studies demonstrating that telomeres shortened during the aging of human both in cell culture and in normal tissues in vivo.[44,45,46,47] In human, meta-analyses have supported a strong relation between short telomeres and mortality risk of ASCVD, particularly at younger ages.[48] Telomerase is a reverse transcriptase that adds new DNA onto the telomeres. Recent evidence indicated that vascular aging can be reverted by telomerase activation, and normal physiological aging can be delayed by systemic viral transduction of telomerase.[49,50,51] Further insight into the underlining mechanisms of telomerase is, therefore, fundamental for both the prevention and the development of treatment for age-related ASCVD.
Mitochondria and superoxide flashes
Vascular endothelial cells aging exhibit a variety of changes in mitochondrial function, dynamics, and morphology, including decreased membrane potential, increased proton leakage, decreased fusion and division rates, increased species of tricarboxylic acid (TCA)-circulating metabolites, dysfunction of electron transport chain (ETC), overproduction of reactive oxygen species (ROS), and changes in AMP: ATP and ADP: ATP ratios.[52] Detection of mitochondrial function and morphology is another novel method for evaluation of vascular aging. Interestingly, superoxide flashes are a novel mechanism for quantal ROS production by individual mitochondria, which are triggered by transient openings of the mitochondrial permeability transition pore (mPTP) and are fueled by electron transfer complexes-dependent superoxide production.[53] A study suggested that superoxide flash is a relatively early and pivotal event of cell metabolism, differentiation, stress response, and aging.[54]
Nucleolus
Scientists have found that about half of the cells age through a gradual decline in the stability of the nucleolus, which is a region of nuclear DNA where key components of protein are synthesized.[55] Maintenance of nucleolar homeostasis is suggested to contribute to counteracting cells aging.[56] Activation of the NF-κB pathway by nucleolar stress and induction of apoptosis by nucleolar sequestration of NF-κB/RelA may emerge as a mechanism of vascular aging.[57] Further studies are necessary for better understanding the relationship between the nucleolar homeostasis and the process of vascular aging.
cfDNA
The study discovered that the distribution of nucleosomes on the cfDNA (cell-free DNA) strand of healthy young people was regular, while the distribution was scattered in the elderly. Moreover, the cfDNA signal of the two transposons began to decrease with age.[58] On this basis, cfDNA can be recognized as a new biomarker of aging, and its alternation can be used to clarify the “real age” of organisms and reflect the health status of the body.
Humanin
Humanin is a new member of the polypeptide family encoded by a short open reading frame in the mitochondrial genome. Studies have showed that humanin decreases with age in several species, including humans, and more interestingly, the offspring of centenarians has higher levels of humanin,[59] which also indicates that humanin is expected to be a new marker for clinical detection of aging in the future.
Ageotype
Recently, scientists have identified four different ageotypes: immunity ageotype, metabolic ageotype, liver dysfunction ageotype, and kidney dysfunction ageotype, by collecting biological samples from 43 subjects, including blood, inflammatory substances, microorganisms, genetic materials, proteins, and byproducts of metabolic processes, and tracking how the samples change over time.[60] Ageotypes may provide a molecular assessment of aging, reflective of lifestyle and medical history, which may ultimately be helpful in detecting and intervening in the vascular aging process.[60]
Perspectives
Vascular aging is a common basis of various ASCVD. In order to delay the process of vascular aging and prevent age-related vascular pathologies, addressing the clinical evaluation of age-related vascular diseases is of critical importance. This review describes the progress of clinical evaluation of vascular aging, including functional evaluation, structural assessment, and cellular molecular biomarkers. Although great progress has been achieved in characterizing aging-induced changes in vascular function, research efforts should persist in this direction to excavate the underlying mechanisms and develop novel methods to evaluate vascular aging, in order for the promotion of vascular health in older adults. In addition, the construction of comprehensive intervention system based on a risk assessment of vascular aging is the hotspot and direction of future research, which will make it possible to better prevent age-related ASCVD and prolong the lifespan and healthspan of the elderly.
Conflict of Interest
The authors declare no competing interests.
Declarations
The manuscript has been read and approved by all the authors.
References
1 Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a “set up” for vascular disease. Circulation 2003; 107: 139–46.10.1161/01.CIR.0000048892.83521.58Search in Google Scholar PubMed
2 Ungvari Z, Tarantini S, Donato AJ, Galvan V, Csiszar A. Mechanisms of Vascular Aging. Circ Res 2018;123:849–67.10.1161/CIRCRESAHA.118.311378Search in Google Scholar PubMed PubMed Central
3 Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Endothelial Function Is Impaired in Patients Receiving Antihypertensive Drug Treatment Regardless of Blood Pressure Level: FMD-J Study (Flow-Mediated Dilation Japan). Hypertension 2017; 70: 790–7.10.1161/HYPERTENSIONAHA.117.09612Search in Google Scholar PubMed
4 Koivistoinen T, Lyytikainen LP, Aatola H, Luukkaala T, Juonala M, Viikari J, et al. Pulse Wave Velocity Predicts the Progression of Blood Pressure and Development of Hypertension in Young Adults. Hypertension 2018;71:451–6.10.1161/HYPERTENSIONAHA.117.10368Search in Google Scholar PubMed
5 Abboud H, Monteiro Tavares L, Labreuche J, Arauz A, Bryer A, Lavados PM, et al. Impact of Low Ankle-Brachial Index on the Risk of Recurrent Vascular Events. Stroke 2019;50:853–8.10.1161/STROKEAHA.118.022180Search in Google Scholar PubMed
6 Rigatelli G, Zuin M, Dell’Avvocata F, Nanjundappa A, Daggubati R, Nguyen T. Non-invasive Evaluation of Fluid Dynamic of Aortoiliac Atherosclerotic Disease: Impact of Bifurcation Angle and Different Stent Configurations. J Transl Int Med 2018; 6: 138–45.10.2478/jtim-2018-0020Search in Google Scholar PubMed PubMed Central
7 de la Cruz-Ares S, Cardelo MP, Gutierrez-Mariscal FM, Torres-Pena JD, Garcia-Rios A, Katsiki N, et al. Endothelial Dysfunction and Advanced Glycation End Products in Patients with Newly Diagnosed Versus Established Diabetes: From the CORDIOPREV Study. Nutrients 2020;12:238.10.3390/nu12010238Search in Google Scholar PubMed PubMed Central
8 Najjar SS, Scuteri A, Shetty V, Wright JG, Muller DC, Fleg JL, et al. Pulse wave velocity is an independent predictor of the longitudinal increase in systolic blood pressure and of incident hypertension in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol 2008;51:1377–83.10.1016/j.jacc.2007.10.065Search in Google Scholar PubMed PubMed Central
9 Park SY, Chin SO, Rhee SY, Oh S, Woo JT, Kim SW, et al. Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus. Diabetes Metab J 2018;42:285–95.10.4093/dmj.2017.0080Search in Google Scholar PubMed PubMed Central
10 Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability. Nat Rev Cardiol 2013;10:143–55.10.1038/nrcardio.2013.1Search in Google Scholar PubMed
11 Gawrys J, Wisniewski J, Szahidewicz-Krupska E, Gajecki D, Lesniewska J, Majda F, et al. Increased Intraplatelet ADMA Level May Promote Platelet Activation in Diabetes Mellitus. Oxid Med Cell Longev 2020;2020:6938629.10.1155/2020/6938629Search in Google Scholar PubMed PubMed Central
12 Gui F, You Z, Fu S, Wu H, Zhang Y. Endothelial Dysfunction in Diabetic Retinopathy. Front Endocrinol (Lausanne) 2020;11:591.10.3389/fendo.2020.00591Search in Google Scholar PubMed PubMed Central
13 Al-Nakhli HH, Petrofsky JS, Laymon MS, Arai D, Holland K, Berk LS. The use of thermal infrared imaging to assess the efficacy of a therapeutic exercise program in individuals with diabetes. Diabetes Technol Ther 2012;14:159–67.10.1089/dia.2011.0187Search in Google Scholar PubMed
14 van Doremalen RFM, van Netten JJ, van Baal JG, Vollenbroek-Hutten MMR, van der Heijden F. Validation of low-cost smartphone-based thermal camera for diabetic foot assessment. Diabetes Res Clin Pract 2019;149:132–9.10.1016/j.diabres.2019.01.032Search in Google Scholar PubMed
15 Selvarani A, Suresh GR. Infrared Thermal Imaging for Diabetes Detection and Measurement. J Med Syst 2019;43:23.10.1007/s10916-018-1140-1Search in Google Scholar PubMed
16 Brzezinski RY, Ovadia-Blechman Z, Lewis N, Rabin N, Zimmer Y, Levin-Kotler L, et al. Non-invasive thermal imaging of cardiac remodeling in mice. Biomed Opt Express 2019;10:6189–6203.10.1364/BOE.10.006189Search in Google Scholar PubMed PubMed Central
17 Englund EK, Langham MC. Quantitative and Dynamic MRI Measures of Peripheral Vascular Function. Front Physiol 2020;11:120.10.3389/fphys.2020.00120Search in Google Scholar PubMed PubMed Central
18 Huegli RW, Schulte AC, Aschwanden M, Thalhammer C, Kos S, Jacob AL, et al. Effects of percutaneous transluminal angioplasty on muscle BOLD-MRI in patients with peripheral arterial occlusive disease: preliminary results. Eur Radiol 2009;19:509–15.10.1007/s00330-008-1168-6Search in Google Scholar PubMed
19 Larsen RG, Thomsen JM, Hirata RP, Steffensen R, Poulsen ER, Frokjaer JB, et al. Impaired microvascular reactivity after eccentric muscle contractions is not restored by acute ingestion of antioxidants or dietary nitrate. Physiol Rep 2019;7:e14162.10.14814/phy2.14162Search in Google Scholar PubMed PubMed Central
20 Englund EK, Langham MC, Ratcliffe SJ, Fanning MJ, Wehrli FW, Mohler ER, 3rd, et al. Multiparametric assessment of vascular function in peripheral artery disease: dynamic measurement of skeletal muscle perfusion, blood-oxygen-level dependent signal, and venous oxygen saturation. Circ Cardiovasc Imaging 2015;8: 10.1161/CIRCIMAGING.114.002673 e002673.Search in Google Scholar PubMed PubMed Central
21 Wu WC, Mohler E, 3rd, Ratcliffe SJ, Wehrli FW, Detre JA, Floyd TF. Skeletal muscle microvascular flow in progressive peripheral artery disease: assessment with continuous arterial spin-labeling perfusion magnetic resonance imaging. J Am Coll Cardiol 2009; 53:2372–7.10.1016/j.jacc.2009.03.033Search in Google Scholar PubMed PubMed Central
22 Englund EK, Rodgers ZB, Langham MC, Mohler ER, 3rd, Floyd TF, Wehrli FW. Simultaneous measurement of macro- and microvascular blood flow and oxygen saturation for quantification of muscle oxygen consumption. Magn Reson Med 2018;79:846–55.10.1002/mrm.26744Search in Google Scholar PubMed PubMed Central
23 Langham MC, Li C, Englund EK, Chirico EN, Mohler ER, 3rd, Floyd TF, et al. Vessel-wall imaging and quantification of flow-mediated dilation using water-selective 3D SSFP-echo. J Cardiovasc Magn Reson 2013;15:100.10.1186/1532-429X-15-100Search in Google Scholar PubMed PubMed Central
24 Juonala M, Viikari JS, Kahonen M, Taittonen L, Laitinen T, Hutri-Kahonen N, et al. Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study. Eur Heart J 2010;31:1745–51.10.1093/eurheartj/ehq141Search in Google Scholar PubMed
25 Lorenz MW, Gao L, Ziegelbauer K, Norata GD, Empana JP, Schmidtmann I, et al. Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration. PLoS One 2018;13:e0191172.10.1371/journal.pone.0191172Search in Google Scholar PubMed PubMed Central
26 Xu Y, Arora RC, Hiebert BM, Lerner B, Szwajcer A, McDonald K, et al. Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging 2014;15:736–46.10.1093/ehjci/jet256Search in Google Scholar PubMed
27 Lind L. Effect of new statin treatment on carotid artery intima-media thickness: A real-life observational study over 10 years. Atherosclerosis 2020; 306: 6–10.10.1016/j.atherosclerosis.2020.06.012Search in Google Scholar PubMed
28 Kim KH, Doh JH, Koo BK, Min JK, Erglis A, Yang HM, et al. A novel noninvasive technology for treatment planning using virtual coronary stenting and computed tomography-derived computed fractional flow reserve. JACC Cardiovasc Interv 2014; 7: 72–8.10.1016/j.jcin.2013.05.024Search in Google Scholar PubMed
29 Kishi S, Giannopoulos AA, Tang A, Kato N, Chatzizisis YS, Dennie C, et al. Fractional Flow Reserve Estimated at Coronary CT Angiography in Intermediate Lesions: Comparison of Diagnostic Accuracy of Different Methods to Determine Coronary Flow Distribution. Radiology 2018;287:76–84.10.1148/radiol.2017162620Search in Google Scholar PubMed PubMed Central
30 Kang EJ, Kim SM, Choe YH, Lee GY, Lee KN, Kim DK. Takayasu arteritis: assessment of coronary arterial abnormalities with 128-section dual-source CT angiography of the coronary arteries and aorta. Radiology 2014;270:74–81.10.1148/radiol.13122195Search in Google Scholar PubMed
31 Shim K, Begum R, Yang C, Wang H. Complement activation in obesity, insulin resistance, and type 2 diabetes mellitus. World J Diabetes 2020;11:1–12.10.4239/wjd.v11.i1.1Search in Google Scholar PubMed PubMed Central
32 Hormel TT, Jia Y, Jian Y, Hwang TS, Bailey ST, Pennesi ME, et al. Plexus-specific retinal vascular anatomy and pathologies as seen by projection-resolved optical coherence tomographic angiography. Prog Retin Eye Res 2020: 100878.10.1016/j.preteyeres.2020.100878Search in Google Scholar PubMed PubMed Central
33 Chua J, Sim R, Tan B, Wong D, Yao X, Liu X, et al. Optical Coherence Tomography Angiography in Diabetes and Diabetic Retinopathy. J Clin Med 2020; 9: 1723.10.3390/jcm9061723Search in Google Scholar PubMed PubMed Central
34 Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM. Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens 2006;20:490–5.10.1038/sj.jhh.1001996Search in Google Scholar PubMed
35 Yang Z, Chen L, Su C, Xia WH, Wang Y, Wang JM, et al. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension. Clin Exp Hypertens 2010;32:444–52.10.3109/10641961003686435Search in Google Scholar PubMed
36 Xia WH, Yang Z, Xu SY, Chen L, Zhang XY, Li J, et al. Age-related decline in reendothelialization capacity of human endothelial progenitor cells is restored by shear stress. Hypertension 2012;59:1225–31.10.1161/HYPERTENSIONAHA.111.179820Search in Google Scholar PubMed
37 Wang JM, Huang YJ, Wang Y, Xu MG, Wang LC, Wang SM, et al. Increased circulating CD31+/CD42-microparticles are associated with impaired systemic artery elasticity in healthy subjects. Am J Hypertens 2007; 20:957–64.10.1016/j.amjhyper.2007.04.005Search in Google Scholar PubMed
38 Wang JM, Su C, Wang Y, Huang YJ, Yang Z, Chen L, et al. Elevated circulating endothelial microparticles and brachial-ankle pulse wave velocity in well-controlled hypertensive patients. J Hum Hypertens 2009;23:307–15.10.1038/jhh.2008.137Search in Google Scholar PubMed
39 Zhang HN, Dai Y, Zhang CH, Omondi AM, Ghosh A, Khanra I, et al. Sirtuins family as a target in endothelial cell dysfunction: implications for vascular ageing. Biogerontology. 2020;21: 495–516.10.1007/s10522-020-09873-zSearch in Google Scholar PubMed
40 Lee SH, Lee JH, Lee HY, Min KJ. Sirtuin signaling in cellular senescence and aging. BMB Rep 2019;52:24–34.10.5483/BMBRep.2019.52.1.290Search in Google Scholar PubMed PubMed Central
41 He X, Zeng H, Chen JX. Emerging role of SIRT3 in endothelial metabolism, angiogenesis, and cardiovascular disease. J Cell Physiol 2019;234:2252–65.10.1002/jcp.27200Search in Google Scholar PubMed PubMed Central
42 He J, Liu X, Su C, Wu F, Sun J, Zhang J, et al. Inhibition of Mitochondrial Oxidative Damage Improves Reendothelialization Capacity of Endothelial Progenitor Cells via SIRT3 (Sirtuin 3)-Enhanced SOD2 (Superoxide Dismutase 2) Deacetylation in Hypertension. Arterioscler Thromb Vasc Biol 2019;39:1682–98.10.1161/ATVBAHA.119.312613Search in Google Scholar PubMed
43 Yu BB, Zhi H, Zhang XY, Liang JW, He J, Su C, et al. Mitochondrial dysfunction-mediated decline in angiogenic capacity of endothelial progenitor cells is associated with capillary rarefaction in patients with hypertension via downregulation of CXCR4/JAK2/SIRT5 signaling. Ebiomedicine 2019;42:64–75.10.1016/j.ebiom.2019.03.031Search in Google Scholar PubMed PubMed Central
44 Kalstad AA, Tveit S, Myhre PL, Laake K, Opstad TB, Tveit A, et al. Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients. BMC Geriatr 2019;19:376.10.1186/s12877-019-1383-9Search in Google Scholar PubMed PubMed Central
45 Mansson KNT, Lindqvist D, Yang LL, Svanborg C, Isung J, Nilsonne G, et al. Improvement in indices of cellular protection after psychological treatment for social anxiety disorder. Transl Psychiatry 2019;9:340.10.1038/s41398-019-0668-2Search in Google Scholar PubMed PubMed Central
46 Astrom MJ, von Bonsdorff MB, Perala MM, Salonen MK, Rantanen T, Kajantie E, et al.. Telomere length and physical performance among older people-The Helsinki Birth Cohort Study. Mech Ageing Dev 2019;183:111145.10.1016/j.mad.2019.111145Search in Google Scholar PubMed
47 Tsoukalas D, Fragkiadaki P, Docea AO, Alegakis AK, Sarandi E, Vakonaki E, et al. Association of nutraceutical supplements with longer telomere length. Int J Mol Med 2019;44:218–226.10.3892/ijmm.2019.4191Search in Google Scholar PubMed PubMed Central
48 Boonekamp JJ, Simons MJ, Hemerik L, Verhulst S. Telomere length behaves as biomarker of somatic redundancy rather than biological age. Aging Cell 2013;12:330–2.10.1111/acel.12050Search in Google Scholar PubMed
49 Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 2011;469:102–6.10.1038/nature09603Search in Google Scholar PubMed PubMed Central
50 Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153:1194–217.10.1016/j.cell.2013.05.039Search in Google Scholar PubMed PubMed Central
51 Vecoli C, Borghini A, Andreassi MG. The molecular biomarkers of vascular aging and atherosclerosis: telomere length and mitochondrial DNA(4977) common deletion. Mutat Res. 2020;784:108309.10.1016/j.mrrev.2020.108309Search in Google Scholar PubMed
52 Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular Senescence: Defining a Path Forward. Cell 2019;179:813–27.10.1016/j.cell.2019.10.005Search in Google Scholar PubMed
53 Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, et al. Superoxide flashes in single mitochondria. Cell 2008;134:279–90.10.1016/j.cell.2008.06.017Search in Google Scholar PubMed PubMed Central
54 Hou T, Wang X, Ma Q, Cheng H. Mitochondrial flashes: new insights into mitochondrial ROS signalling and beyond. J Physiol 2014;592:3703–13.10.1113/jphysiol.2014.275735Search in Google Scholar PubMed PubMed Central
55 Li Y, Jiang Y, Paxman J, O’Laughlin R, Klepin S, Zhu Y, et al. A programmable fate decision landscape underlies single-cell aging in yeast. Science 2020;369:325–9.10.1126/science.aax9552Search in Google Scholar PubMed PubMed Central
56 Ren X, Hu B, Song M, Ding Z, Dang Y, Liu Z, et al. Maintenance of Nucleolar Homeostasis by CBX4 Alleviates Senescence and Osteoarthritis. Cell Rep 2019;26:3643–56 e7.10.1016/j.celrep.2019.02.088Search in Google Scholar PubMed
57 Chen J, Stark LA. Insights into the Relationship between Nucleolar Stress and the NF-kappaB Pathway. Trends Genet 2019;35:768–80.10.1016/j.tig.2019.07.009Search in Google Scholar PubMed
58 Teo YV, Capri M, Morsiani C, Pizza G, Faria AMC, Franceschi C, et al. Cell-free DNA as a biomarker of aging. Aging Cell 2019;18:e12890.10.1111/acel.12890Search in Google Scholar PubMed PubMed Central
59 Yen K, Mehta HH, Kim SJ, Lue Y, Hoang J, Guerrero N, et al. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY) 2020;12:11185–99.10.18632/aging.103534Search in Google Scholar PubMed PubMed Central
60 Ahadi S, Zhou W, Schussler-Fiorenza Rose SM, Sailani MR, Contrepois K, Avina M, et al. Personal aging markers and ageotypes revealed by deep longitudinal profiling. Nat Med 2020;26:83–90.10.1038/s41591-019-0719-5Search in Google Scholar PubMed PubMed Central
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Articles in the same Issue
- Editorials
- Potential new therapeutic intervention for ischemic stroke
- From critical care nephrology to critical care blood purification
- Commentary
- ACEI/ARB drug therapy in COVID-19 patients: Yes or no?
- Review Articles
- The use of electroencephalography in patients with sepsis: A review of the literature
- Progress of clinical evaluation for vascular aging in humans
- Advances in the diagnosis and treatment of achalasia of the cardia: A review
- Original Articles
- Age related differences in acute coronary syndrome: An observation at a central hospital in Vietnam
- Analysis of digestive endoscopic results during COVID-19
- Promyelocytic leukemia antigen expression: A histological marker for primary biliary cholangitis diagnosis?
- Experiences on the administration of botulinum toxin in movement disorders
- Letters to Editor
- Recovery from acute kidney injury is a potent predictor of survival and good neurological outcome at discharge after out-of-hospital cardiac arrest: Fact or fiction
- SARS-CoV-2 and acute diverticulitis: The expanding gastrointestinal manifestations of COVID-19 infection
