Research advances on clinical evaluation of vascular aging / 中华老年医学杂志

Vascular senescence is one of the important causes of cardiovascular diseases.Functional evaluation of vascular endothelial cells and smooth muscle cells is an important means to identify vascular senescence.A convenient and effective vascular senescence assessment method applicable to clinical practice can identify high-risk populations early and is of great significance to the prevention, treatment and prognosis evaluation of related diseases.

Progress in research on autophagy in vascular aging-related diseases / 中华老年医学杂志

Aging begins in the early stages of life and is an irreversible process in which wide-ranging and gradual functional declines occur with age in various organs of the body.Vascular aging, as a part of the overall aging process, plays an important role in the occurrence and development of vascular senescence-related diseases.Autophagy maintains homeostasis of the intracellular environment via degradation of damaged, denatured, or senescent proteins and organelles.Studies have found that basal autophagy is critical in regulating normal vascular function.However, abnormal autophagy may contribute to vascular aging and diseases associated with it.The purpose of this paper is to review recent progress on autophagy in vascular aging and its related diseases.

Effect of Ginseng Radix et Rhizoma， Notoginseng Radix et Rhizoma， and Chuanxiong Rhizoma Extract on Mitochondrial Oxidative Stress in Hydrogen Peroxide-induced Endothelial Cell Aging / 中国实验方剂学杂志

Objective:To observe the effect of Ginseng Radix et Rhizoma， Notoginseng Radix et Rhizoma， and Chuanxiong Rhizoma extract （GNC） on mitochondrial oxidative stress in hydrogen peroxide （H₂O₂）-induced aging of human umbilical vein endothelial cells （HUVECs）， and explore the therapeutic mechanism of GNC on aging HUVECs. Method:The HUVECs were classified into the control group （control）， H₂O₂ model group （H₂O₂）， H₂O₂ + DMSO group （DMSO， 1 mL·L^-1）， resveratrol group （Resv， 8 μmol·L^-1）， and low- （200 mg·L^-1）， medium- （300 mg·L^-1）， and high-dose （400 mg·L^-1） GNC （GNC-L， GNC-M， and GNC-H） groups. Except control group and H₂O₂ group， the other groups were intervened with corresponding agents. Subsequently， 300 μmol·L^-1 H₂O₂ was given to other groups except the control group for 4 h to induce aging， and then the cells were cultured in normal media for 24 h. The aging degree， cell cycle， and mitochondrial reactive oxygen species （mtROS） level were determined by SA-<italic>β</italic>-galactosidase （SA-<italic>β</italic>-Gal） staining， flow cytometry， and MitoSox red fluorescence staining， respectively. JC-10 was used as a fluorescent probe to detect the changes in mitochondrial membrane potential， and Western blot was performed to detect the expression of manganese superoxide dismutase （MnSOD） and p-p66 proteins. Result:The SA-<italic>β</italic>-gal staining results showed that H₂O₂ group had increased blue-stained cells compared with other groups （<italic>P</italic><0.01）. Compared with those in the control group， the ratio of G₀/G₁ phase cells significantly increased （<italic>P</italic><0.05） and that of G₂/M phase cells decreased （<italic>P</italic><0.05） in the H₂O₂ group. Compared with those in the H₂O₂ group， the proportion of G₀/G₁ cells decreased （<italic>P</italic><0.05） while that of G₂/M cells increased （<italic>P</italic><0.05） in GNC-H groups and Resv group. The fluorescence staining for determining mitochondrial ROS level showed that the H₂O₂ group had weakened fluorescence intensity than the control， GNC-H， and GNC-M groups （<italic>P</italic><0.05）. The mitochondrial membrane potential fluorescence intensity of the H₂O₂ group was weaker than that of the control， GNC-H， GNC-M， and GNC-L groups （<italic>P</italic><0.01）， as well as the Resv group （<italic>P</italic><0.05）. Western blot showed that the protein level of MnSOD was significantly lower in the H₂O₂ group than in the control， GNS-H， and GNS-M groups （<italic>P</italic><0.05）， whereas the protein level of p-p66 showed an opposite trend （<italic>P</italic><0.01）， indicating that the medication can alleviate the intracellular mitochondrial oxidative stress. Conclusion:GNC can delay the H₂O₂-induced aging of vascular endothelial cells. The GNC intervention significantly regulated the mitochondrial ROS， mitochondrial membrane potential， and related proteins MnSOD and p-p66 to alleviate oxidative stress. Chinese medicinal materials may delay the aging of vascular endothelial cells by inhibiting mitochondrial oxidative stress.

The mechanism of NLRP3 inflammasome affecting vascular aging and the development of related drugs / 药学学报

Nucleotide binding oligomerization domain (NOD)-like receptor protein 3, NLRP3) inflammasomes regulate the secretion of caspase-1, interleukin-18 (IL-18), IL-1β, and other cytokines, and participates in aging. In recent years, it has been found that NLRP3 inflammasomes are abnormally activated in aging heart and vessels, and inhibition of NLRP3 inflammasomes can alleviate heart aging and vascular aging. This review summarizes the research of NLRP3 inflammasome in heart and vascular aging, and the related drugs to promote the discovery of the mechanism of NLRP3 inflammasome in heart and vascular aging and the development of related drugs.

Impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging / 中华心血管病杂志

Objective@#To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA).@*Methods@#This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants′ characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values.@*Results@#The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24).@*Conclusion@#The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.

Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts on intestinal flora of vascular aging mice induced by high glucose and high lipid / 中国中药杂志

The aim of this paper was to observe the changes of intestinal flora in vascular aging mice, in order to explore the relationship between vascular aging and intestinal flora and the effects of extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on intestinal flora of vascular aging mice. A model of vascular aging in mice was induced through intrape-ritoneal injection with streptozotocin(STZ) combined with high-fat diet. Biochemical detection was performed on serum cholesterol(CHO), triglyceride(TG), high-density liptein cholesterol(HDL-C), low-density liptein cholesterol(LDL-C) and blood glucose(GLU). HE staining was used to detect mice thoracic aorta morphology, and the expressions of cyclin-dependent kinase inhibitor 2 A(p16) and cyclin-dependent kinase inhibitor 1 A(p21) protein in mice thoracic aorta were detected by Western blot. The 16 S rDNA gene of mice intestinal flora was detected by Illumina MiSeq high-throughput sequencing technology to explore the changes of intestinal flora in each group. The results demonstrated that the GLU level in low-dose and high-dose TCM groups decreased, but with unobvious changes in blood lipid indexes. Metformin could significantly decrease the levels of GLU(P<0.01), CHO and LDL-C in mice(P<0.05). Intravascular injury was not obvious in each drug group, and the expressions of p16 and p21 protein were significantly decreased(P<0.05). The intestinal flora of each group was mainly composed of Firmicutes(F) and Bacteroidetes(B) at the level of the phylum, but the B/F ratio was different from that of the youth group and the blank control group. The B/F ratio of the model group was significantly lower(P<0.01), and compared with the model group, the B/F ratio of the high-dose group and the metformin group was signi-ficantly higher(P<0.05). There were dominant and differential floras in the intestine of each group of mice. The results showed that extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma could improve the intestinal flora structure and create a good intestinal environment by increasing the B/F ratio, which provides a new possible pathway for lowering blood glucose and blood lipids and delaying vascular aging.

Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice / 中国实验方剂学杂志

Objective::To investigate the effects of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts (GNC) on the protein expression of α-smooth muscle actin (α-SMA) and runt-related transcription factor2(Runx2) after high glucose-induced vascular aging in mice, and elucidate the protective mechanism of GNC in delaying vascular aging. Method::Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin (STZ). After successful modeling, the mice received high-fat diet for 7 months, and then they were randomly divided into model group, GNC low-dose and high-dose groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). The drug was given by intragastric administration once a day for 9 weeks. Seven days before tissues collection, a new batch of 4-week-old male C57BL/6 mice were purchased and fed normally for 1 week as a youth group. The general condition of the mice was observed. Morphological changes of the common carotid artery in mice were determined by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Masson trichromatic staining was used to observe the fibrosis of common carotid artery in mice. The expression levels of matrix metalloproteinases-2 (MMP-2), cyclin-dependent kinase inhibitor 2A (p16), cyclic-dependent kinase inhibitor 1A (p21), α-SMA and Runx2 in the common carotid arteries of mice were detected by immunohistochemistry. Result::The results of HE, TEM and Masson showed that there was almost no change in the inimal and adventitial thickness, ultrastructure and relative contents of collagen and elastic fibers in the common carotid arteries of mice between the youth group and normal control group. As compared with the normal control group, the intima of the common carotid artery in the model group was not smooth, the endothelial cells were almost completely detached, the cytoplasm was lysed, the inner elastic membrane became thinner, fractured, or even detached, and the proliferating collagen fibers sneaked into the tunica media. The hyperplasia of tunica media and tunica adventitia was obvious and disordered (P<0.01). The vascular smooth muscle cells showed deformations, protuberances, bifurcations, and even fragmentation, and focal necrosis was observed. There were significantly more vacuoles, lysosomes, and obvious autophagy vesicles. The relative content of collagen and elastic fibers in vascular walls increased significantly (P<0.01). Compared with the model group, the above situation was relieved in each administration group (P<0.01). The results of immunohistochemistry showed that high glucose induced high expression of MMP-2, p16, p21 and Runx2 in the common carotid arteries(P<0.01), low expression of α-SMA(P<0.01), and the protein expression tended to be normal after drug intervention(P<0.05, P<0.01). Conclusion::High glucose can induce the aging of common carotid artery in mice and change the expression of α-SMA and Runx2 proteins. The Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can delay vascular aging by regulating the protein expression of α-SMA and Runx2.

Mechanism of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts in Delaying High Glucose-induced Vascular Calcification in Mice / 中国实验方剂学杂志

Objective::To investigate the protective effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts on vascular calcification induced by high glucose in mice by observing the expression of osteopontin (OPN) and smooth muscle 22α (SM22α) as well as vascular calcium deposition in the common carotid artery and thoracic aorta of mice. Method::Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin(STZ), and fed on a high-fat diet for 7 months. Then, the mice were randomly divided into model group, low-dose and high-dose Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). Each group was intragastrically administered once a day for 9 weeks. The changes in blood glucose were measured. Seven days before the end of the administration, a group of 4-week old male C57BL/6 mice were purchased and fed normally for one week as a youth group. At the end of the administration, the common carotid artery and thoracic aorta tissues of the mice were collected. Von Kossa staining was used to determine the degree of calcium deposition in the common carotid artery and thoracic aorta. The expression levels of OPN and SM22α protein in the common carotid artery and thoracic aorta were detected by immunohistochemistry. The expression of OPN and SM22α protein in the common carotid artery of mice was determined by Western blot. Result::As compared with the young group, the blood glucose of the normal control group was slightly increased without statistical difference, the common carotid artery and thoracic aorta were uniformly stained, and no black granular precipitate was observed. As compared with the normal control group, the blood glucose of the model group was increased (P<0.01), with a large amount of brown-black particles deposited in the intimal elastic fibers, showing obvious calcium salt deposition. As compared with the model group, blood glucose was significantly decreased in each administration group (P<0.05, P<0.01), and the degree of vascular calcium salt deposition was significantly reduced. There were no significant changes in expression levels of OPN protein and SM22α protein in the common carotid artery and thoracic aorta between the youth group and normal control group. As compared with the normal control group, the expression of intimal OPN protein in the common carotid artery and thoracic aorta of the model group was positive, SM22α protein expression was weakly positive, and the gray value of OPN protein expression in the common carotid artery was significantly increased (P<0.01), while the gray value of SM22α protein was decreased significantly (P<0.01). As compared with the model group, the expression levels of intimal OPN protein and SM22α protein in the common carotid artery and thoracic aorta of each administration group were significantly improved, and the gray value of OPN protein expression in the common carotid artery was reduced (P<0.05, P<0.01), while SM22α protein expression was significantly increased (P<0.01). Conclusion::High glucose can induce calcification of common carotid artery and thoracic aorta in mice and accelerate vascular aging. This formation process may be related to the expression of OPN and SM22α. Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can reduce vascular calcification and delay vascular aging by regulating the expression of OPN and SM22α.

Impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging / 中华心血管病杂志

Objective: To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA). Methods: This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants' characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values. Results: The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24). Conclusion: The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.

Extracts from Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma in Delaying High Glucose-induced Vascular Senescence in Mice / 中国实验方剂学杂志

Objective: To investigate the protective effect of extracts from Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on vascular senescence induced by high glucose in mice from adenosine 5'-monophosphate (AMP)-activated protein kinase/mechanistic target of rapamycin (AMPK/mTOR) pathway. Method: A total of 130 male C57BL/6 mice were randomly divided into control group and high glucose group. The high glucose group was intraperitoneally injected with streptozocin(STZ) and fed with a high-fat diet continuously for seven months. Mice were divided into 4 groups:model group, low-dose extracts from Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma(0.819 g·kg-1) group, high-dose extracts from Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma group (1.638 g·kg-1) and metformin group (150 mg·kg-1), and intragastrically administered once a day for nine weeks. The changes in body weight and blood glucose were measured. At the end of the administration, htoxylin eosin(HE) was performed for the detection of aortic morphology, and the expressions of cyclin-dependent kinase inhibitor 2A (p16), cyclin-dependent kinase inhibitor 1A (p21), AMPK, p-AMPK, mTOR, p-mTOR, liver kinase B1 (LKB1), p-LKB1, Ribosomal protein s6 kinase (p70s6k) and p-p70s6k proteins in mouse aorta were detected by Western blot. Result: Compared with blank group, mice in model group had lower body weight and higher blood glucose (PPPPPPPPPPPConclusion: High glucose can induce vascular senescence, and extracts from Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma can improve vascular aging induced by high glucose through AMPK/mTOR pathway.

Clinical Efficacy by Kidney Tonifying and Essence Strengthening Method in Regulating Pulse Wave Velocity to Delay Physiological Vascular Aging / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of kidney tonifying and essence strengthening method in delaying physiological vascular aging. Method: Sixty-two subjects who completed the study were randomly divided into experimental group (31 cases) and control group (31 cases) with the matching research method. The experimental group was treated with kidney tonifying and essence strengthening recipe orally for 24 weeks, while the control group was not interfered with traditional Chinese medicine (TCM). Score of TCM syndrome in kidney deficiency syndrome, pulse wave velocity, intima-media thickness, plasma homocysteine level and serum superoxide dismutase level were evaluated before and after treatment. Result: Compared with before treatment period, the score of TCM syndrome in kidney deficiency syndrome, pulse wave velocity and plasma homocystenine level decreased, while the serum superoxide dismutase level increased in the experimental group after treatment (PPPPPConclusion: The kidney tonifying and essence strengthening method may delay the aging of physiological blood vessels caused by aging.

Effect of microRNA-34a/SIRT1/p53 signal pathway on notoginsenoside R₁ delaying vascular endothelial cell senescence / 中国中药杂志

This study aimed to investigate the effect of notoginsenoside R₁ in delaying H₂O₂-induced vascular endothelial cell senescence through microRNA-34a/SIRT1/p53 signal pathway. In this study， human umbilical vein endothelial cells(HUVECs) were selected as the study object; the aging model induced by hydrogen peroxide(H₂O₂) was established， with resveratrol as the positive drug. HUVECs were randomly divided into four groups， youth group， senescence model group， notoginsenoside R₁ group and resveratrol group. Notoginsenoside R₁ group and resveratrol group were modeled with 100 μmoL·L⁻¹ H₂O₂ for 4 h after 24 h treatment with notoginsenoside R₁(30 μmoL·L⁻¹) and resveratrol(10 μmoL·L⁻¹) respectively. At the end， each group was cultured with complete medium for 24 h. The degree of cellular senescence was detected by senescence-associated β-galactosidase(SA-β-Gal) staining kit， the cell viability was detected by cell counting kit-8， the cell cycle distribution was analyzed by flow cytometry， and the cellular SOD activity was detected by WST-1 method in each group. The expressions of SIRT1， p53， p21 and p16 proteins in HUVECs were detected by Western blot. In addition， the mRNA expressions of miRNA-34a， SIRT1 and p53 in HUVECs were assayed by Real-time PCR. These results indicated that notoginsenoside R₁ significantly reduced the positive staining rate of senescent cells， enhanced the cell proliferation capacity and intracellular SOD activity， decreased the proportion of cells in G₀/G₁ phase， and increased the percentage of cells in S phase simultaneously compared with the senescence model group. Moreover， notoginsenoside R₁ decreased the mRNA expressions of miRNA-34a and p53 and the protein expression of p53， p21 and p16.At the same time， notoginsenoside R₁ increased the protein and mRNA expressions of SIRT1. The differences in these results between the senescence model group and the notoginsenoside R₁ group were statistically significant(<0.05). However， there was not statistically significant difference in these results between the notoginsenoside R₁ group and the resveratrol group. In conclusion， the senescence of endothelial cells induced by H₂O₂ can be used as a model for studying aging. Notoginsenoside R₁ has an obvious anti-aging effect on vascular endothelial cells in this study. The possible mechanism is that notoginsenoside R₁ can delay the senescence process of vascular endothelial cells induced by H₂O₂ by regulating microRNA-34a/SIRT1/p53 signal pathway.

The role of micro RNAs in aging of vascular smooth muscle cells / 中华老年医学杂志

Vascular aging could influence the development threshold,process,severity and prognosis of various cardiovascular diseases.Thus,it is one of the most important risk factor responsible for the high mortality of cardiovascular diseases.The vascular smooth muscle cell is an essential component of vessel wall,and is the main basis for cell biological and pathological changes of the vasculature.The structure and function of vascular smooth muscle cell play a key role in vascular aging.Recently,relationships of microRNAs with aging-related diseases have been studied as a research hot spot.We would summarize the role of microRNAs in the aging process of vascular smooth muscle cell.Besides,we would also discuss how to analyze the role of microRNAs in cardiovascular diseases.

New Aging Index Using Signal Features of Both Photoplethysmograms and Acceleration Plethysmograms / 대한의료정보학회지

OBJECTIVES: Acceleration plethysmograms (APGs) are obtained by taking the second derivative of photoplethysmograms (PPGs) and are noninvasive circulatory signals related to risk factors for atherosclerosis with age. There has been growing interest in the development of mobile devices to collect and analyze PPG single features for ambulatory health monitoring. The present study aimed to extract a new feature from the morphologies of APG and PPG signals to classify the dominant indices related to the pulsatile volume of blood in tissue according to age. METHODS: Ten APG and 14 PPG indices were simultaneously extracted. All indices were compared via Pearson correlation coefficients (r) and a regression analysis. We introduced a combined index extracted from both the PPG and APG indices defined as the inflection point area plus the d_peak (IPAD). The participants included 93 healthy adults aged 36–86 years with a mean ± standard deviation age of 57.43 ± 11.99 years. RESULTS: The d_peak and age index for the APG indices were significantly correlated with age (r = −0.408, p < 0.0001 and r = 0.296, p = 0.0039, respectively). Only the A1 time for PPG indices was moderately correlated with age (r = −0.247, p = 0.017). The stiffness index, including individual height information, was not related to age (r = −0.031, p = 0.7713). However, the combined IPAD index was significantly more correlated with age (r = 0.56, p < 0.001) than the other indices. CONCLUSIONS: The proposed index outperformed the other 24 indices for evaluating vascular aging. We suggest that the IPAD is a significant factor related to the clinical information embedded in the PPG waveform.

Role of noncoding RNA in vascular injury, remodeling and aging / 中国药理学通报

Non-coding RNAs ( ncRNA ), including ribosomal RNA( rRNA), transfer RNA( tRNA), MicroRNA ( miRNA), long noncoding RNA(lncRNA) and small nucleolar RNA(snoR-NA), are a class of RNA that have multiple functions and are not translated to proteins. MicroRNA and lncRNA are involved in the injury, remodeling and aging of blood vessels, and it is necessary to understand the regulatory roles of MicroRNA and lncRNA in these processes. It is reported that MicroRNA and lncRNA are not only participated in the regulation of oxidative response, inflammation, cell proliferation and migration, and phenotype transition, they are also involved in the regulation of gene expression by conducting different mechanisms, including transcriptional regulation, post-transcriptional modification and chromatin remodeling. These aspects of regulation by MicroRNA and lncRNA are related to cardiovascular diseases, such as ath-erosclerosis, hypertension, myocardial infarction, stroke, pul-monary hypertension and diabetes, and thus provide a new way for genetic diagnosis and therapy of cardiovascular diseases.

Effects of ginseng, notoginseng, and Chuanxiong Rhizoma extracts on cytoskeleton protein of replicative senescence vascular smooth muscle cells / 中国中药杂志

To observe the effect of extracts of ginseng, notoginseng, and Chuanxiong Rhizome on the cytoskeleton protein F-actin and G-actin of the replicative senescence vascular smooth muscle cells, with human aortic smooth muscle cells (HASMC) as the research object, and the replicative senescence 9th generation cells as the senescence models, the experiment was divided into youth group (5th generation cells), model group (9th generation cells), Chinese medicine low dose group (100 mg•L⁻¹), middle dose group (200 mg•L⁻¹), and high dose group (400 mg•L⁻¹) and resveratrol group (10 μmol•L⁻¹). The intervention time was 48 h. β-Galactosidase specific staining method was used to calculate the ratio of blue dyeing cells. CCK-8 method was used to detect the cells proliferation. The flow cytometry was used to analyze the cell cycle. Immunofluorescent staining was used to observe morphological changes of F-actin and G-actin. The western blot assay was used to determine the expression of F-actin protein. Compared with the model group, the Chinese medicine groups and resveratrol group significantly reduced the number of blue dyeing cells, improved the ability of cells proliferation, reduced the number of cells in G0/G1 phase, increased the number of cells in S phase, and reduced the protein expression of F-actin and the formation of stress fibers, with obvious intervention effect and statistically significant difference. Therefore, the replicative senescence vascular smooth muscle cells can be used as the models for senescence research, with significant changes in morphology and protein expression of cytoskeleton protein F-actin and G-actin in the process of cells aging. The extracts of ginseng, notoginseng, and Chuanxiong Rhizome have obvious intervention effect on F-actin and G-actin, and it might be indirectly associated with delaying the aging of blood vessels.

Wave Detection in Acceleration Plethysmogram / 대한의료정보학회지

OBJECTIVES: Acceleration plethysmogram (APG) obtained from the second derivative of photoplethysmography (PPG) is used to predict risk factors for atherosclerosis with age. This technique is promising for early screening of atherosclerotic pathologies. However, extraction of the wave indices of APG signals measured from the fingertip is challenging. In this paper, the development of a wave detection algorithm including a preamplifier based on a microcontroller that can detect the a, b, c, and d wave indices is proposed. METHODS: The 4th order derivative of a PPG under real measurements of an APG waveform was introduced to clearly separate the components of the waveform, and to improve the rate of successful wave detection. A preamplifier with a Sallen-Key low pass filter and a wave detection algorithm with programmable gain control, mathematical differentials, and a digital IIR notch filter were designed. RESULTS: The frequency response of the digital IIR filter was evaluated, and a pulse train consisting of a specific area in which the wave indices existed was generated. The programmable gain control maintained a constant APG amplitude at the output for varying PPG amplitudes. For 164 subjects, the mean values and standard deviation of the a wave index corresponding to the magnitude of the APG signal were 1,106.45 and +/-47.75, respectively. CONCLUSIONS: We conclude that the proposed algorithm and preamplifier designed to extract the wave indices of an APG in real-time are useful for evaluating vascular aging in the cardiovascular system in a simple healthcare device.

Are Vascular Aging and Atherosclerosis Synonymous?

The development of plaques along the inner layer of arterial walls is known as atherosclerosis. Atherosclerotic plaques can become hardened by calcium deposition and fibrous tissue of the arterial wall may proliferate leading to arteriosclerosis. In a typical textbook, arteriosclerosis only has three categories-atherosclerosis, Monckeberg medial calcific sclerosis, and arteriolosclerosis, leaving out vascular aging when in fact, aging is the strongest risk factor for atherosclerosis. Thus, vascular aging is often confused with atherosclerosis. Up to now, there has been no appropriate pathological term for vascular aging. And arteriosclerosis is different from vascular aging, as atherosclerosis includes some components of pathologic aging. But in actuality, physiological aging and pathological aging can not be clearly distinguished. Therefore, in terms of aging, arteriosclerosis is included in vascular aging. More research is required to define vascular aging.

Antihypertensive Therapy Considering the Prevention of Vascular Aging

Considering that an aging population is increasing due to a low birth rate in most developed nations, the maintenance of healthy state and physical and social activities is needed to maintain the national productivities. Among the diseases which deprive elderly people of activities and impose medical and care expenditure, cardiovascular diseases such as stroke, ischemic heart disease, heart failure and renal failure take major parts. These cardiovascular diseases occur based on the development and progression of arteriosclerotic vascular lesions, namely, vascular aging. Because hypertension is a major risk factor for vascular aging, the adequate control of blood pressure is pivotally important in order to prevent the incidence of cardiovascular events in the later stage of life. This is also concerned with the socio-economical issues and national productivity.

EXERCISE AND PREVENTION OF ARTERIOSCLEROSIS IN ELDERLY PEOPLE / 体力科学

Central arterial distensibility decreases with age-related changes in the arterial wall, and as a result, systolic blood pressure and/or pulse pressure (difference of systolic pressure and diastolic pressure) may increase in the elderly. Systolic hypertension and increased pulse pressure are known to be independent risk factors of cardiovascular and cerebrovascular diseases. Decreased distensibility of the central arteries may also cause the deterioration of circulatory function and physical ability in the elderly. Several studies have shown that central arterial distensibility is increased in athletes, and that daily physical activity is positively related to central arterial distensi bility in not only young but also elderly people. It has also been shown that relatively short-term and low-intensity exercise training could improve central arterial distensibility even in the elderly. Thus, physical exercise may have an effect on retarding age-related changes of the central arteries. To establish higher quality of life by preventing cardiovascular and cerebrovascular diseases and by improving circulatory function and physical ability in the elderly, further studies are needed to investigate the detailed mechanism and the appropriate amount and or intensity of exercise in improving central arterial distensibility.