Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients

Jun Xu; Feng-Feng Pan; Chan-Chan Xu; Yuan Zhong; Ting-Jun Hu; Guo-Xiang Fu

doi:10.2991/artres.k.191125.001

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Volume 25, Issue 1-2, June 2019, Pages 65 - 69

Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients

Authors

Jun Xu, Feng-Feng Pan, Chan-Chan Xu, Yuan Zhong, Ting-Jun Hu, Guo-Xiang Fu^*

Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yi Shan Road, Shanghai, P R China

^*Corresponding author. Email: fuguoxiang888@163.com

Corresponding Author

Guo-Xiang Fu

Received 21 November 2019, Accepted 24 November 2019, Available Online 4 December 2019.

DOI: 10.2991/artres.k.191125.001 How to use a DOI?
Keywords: Arterial stiffness; cathepsin L; geriatric patients
Abstract: Background: Cathepsin L (Cat L) is involved in the regulation of vascular aging processes. The aim of this study was to evaluate the relationship between plasma Cat L level and arterial stiffness marker through brachial-ankle pulse wave velocity (baPWV) in geriatric patients.

Methods: Cross-sectional study with 502 people were selected from a population of 2250 people aged over 65 years old, from three different basic health zones of Shanghai. Blood samples were collected, and the baPWV was measured with the SphygmoCor system. The geriatric patients with baPWV values >20 m/s were defined as the high arterial stiffness group.

Results: In total, 248 (49.4%) of the 502 geriatric patients in this study were in the high arterial stiffness group. The high arterial stiffness group were older (p = 0.006) and had higher prevalence of hypertension (p = 0.020), coronary heart disease (CHD) (p = 0.037), higher systolic blood pressure (SBP) (p = 0.018), pulse pressure (p = 0.017), plasma Cat L (p = 0.002) and logarithmically transformed C-reactive protein (p = 0.023) levels than those in the low arterial stiffness group. Multivariable forward stepwise regression analysis showed that Cat L (β = 0.418, p = 0.011) and hypertension (β = 0.217, p = 0.029) were associated with baPWV values in geriatric patients. Moreover, an increased plasma Cat L level (odds ratio (OR): 1.048; 95% confidence interval (CI): 1.043–1.169; p = 0.018) was an independent factor for arterial stiffness among the geriatric patients.

Conclusion: In this study, plasma Cat L level was positively correlated with arterial stiffness in geriatric patients.
Copyright: © 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

1. INTRODUCTION

Advanced aging prompted vascular aging. As the consequence of vascular aging, arterial stiffness constitutes a potential risk factor for increased cardiovascular mortality in the elderly patients. Its role in the development of Cardiovascular Diseases (CVD) has been more emphatically studied in the past years [1]. Indirect ways to analyze arterial stiffness have been widely studied, Pulse Wave Velocity (PWV) is considered gold standard to evaluate arterial stiffness and is an independent marker of the presence of atherosclerotic cardiovascular diseases. Brachial-ankle PWV (baPWV), an index combining elastic and muscular peripheral arterial stiffness, is a conventional and noninvasive screening method to identify patients at high risk of cardiovascular disease [2,3].

Cysteine protease cathepsins, such as cathepsin L (Cat L), cathepsin K (Cat K), cathepsin S (Cat S), and cathepsin V (Cat V)—are potent elastases and collagenases, play essential roles in the pathogenesis of atherosclerosis in humans and animals [4,5]. In recent decades Cat L has proven to be one of the most valuable gene of aging research [6]. Previous research found that polymorphism in the human Cat L promoter was associated with hypertension [7]. The content and activity of plasma Cat L were increased with age in healthy people [8,9]. Moreover, the plasma Cat L level was correlated with mortality in older adults [10]. We hypothesized that Cat L was associated with arterial stiffness in human. This current study was to determine the relationship between plasma Cat L levels and arterial stiffness measured by baPWV among geriatric patients.

2. MATERIALS AND METHODS

2.1. Participants and Anthropometric Measurements

The present analysis was an on-going observational multiple-center cross-sectional study recruiting elderly subjects (≥65 years old) in the Shanghai (registry number: ChiCTR-ROC-17013247). Individuals were excluded if they were with rheumatic heart disease, valve heart disease, dilated cardiomyopathy, renal failure, stroke (within 3 months), acute and chronic infections, autoimmune disease and tumor. Between June and October 2018, 502 elderly volunteers aged 65 years or older in Southern Shanghai were enrolled into this study. The present study was approved by the ethics committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (Shanghai, China). We gave each participant informed consent to the procedure and preserved their anonymity.

In this cross-sectional study, standard structured questionnaire was carried out to obtain the medical and family history including history of hypertension, diabetes, heart disease, drug use, etc. Clinical examination included height, weight, and Body Mass Index (BMI) was calculated as the weight in kilograms divided by the height in meters squared. Furthermore, Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) was measured in the morning using standard mercury sphygmomanometers. Blood pressure were taken three times at 5-min intervals and were averaged for analysis. Hypertension was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg, or the diagnosis of hypertension was documented in a medical record. The diagnosis of stable Coronary Heart Disease (CHD) was based on the clinical history of chest distress/pain, electrocardiogram indicating myocardial ischemia and CT coronary angiography indicating coronary artery occlusion. Type 2 diabetes mellitus was considered if fasting plasma glucose (FBG) ≥126 mg/dL or random plasma glucose ≥198 mg/dL or using diabetes medication. A person was regarded as dyslipidemia if total cholesterol (TC) >200 mg/dL, or low-density lipoprotein-cholesterol (LDL-C) >120 mg/dL, or high-density lipoprotein cholesterol (HDL-C) <40 mg/dL in men and <50 mg/dL in women, or triglycerides (TG) >150 mg/dL [11,12].

2.2. Biochemical Assessment

Venous blood samples from participants were collected after 8 h of fasting. Each fasting blood sample was immediately centrifuged at 3000 g for 10 min. FBG, TC, TG, HDL-C, LDL-C, creatinine and C-Reactive Protein (CRP) were measured using an autoanalyzer (COBAS Integra 800, Roche Diagnostics, Basel, Switzerland).

2.3. Enzyme-linked Immunosorbent Assay

Plasma levels of human Cat L, Cat V, Cat K and Cat S were measured by Enzyme-linked Immunosorbent Assay (ELISA) according to a protocol provided by the manufacturer (Bender Med System, Burlingame, CA, USA). Briefly, 100 μl of diluted human plasma (2:1) samples and 50 μl of biotin-conjugated antibodies were added to 96-well ELISA plates coated with antibody overnight, followed by overnight incubation. A standard curve was created from each plate as recommended using o-phenylenediamine dihydrochloride (OPD) (Sigma, Saint Louis, USA), and a representative of three independent measurements was presented [8,13].

2.4. Brachial-Ankle Pulse Wave Velocity Measurements

Brachial-Ankle PWV was measured by Oscillometry-based device (BP-203RPE III; Omron Colin Co., Ltd., Tokyo, Japan). Briefly, each subject was laid in the supine position with PWV cuffs wrapped around both ankles and upper arms. The pulse waveforms were recorded by trained research staff after resting for at least 5 min, and the highest baPWV was recorded for further analysis [3].

2.5. Statistical Analysis

Data were tested with the Kolmogorov–Smirnov test for normal distribution. CRP showed skewed non-normally distributions, and therefore were recalculated by logarithm transformation to base 10. All data were presented as means ± standard deviations. The comparison between groups was performed with unpaired student’s t-test for continuous variables and Chi-square test for categorical variables. The association between clinical variables and baPWV values was evaluated by univariable linear regression analysis and multivariate logistic regression analysis (adopted factors: hypertension, CHD, pulse pressure, age, CRP and Cat L). The results were analyzed using Statistical Product and Service Solutions version 19.0 software (SPSS Inc., Chicago, IL, USA) and p < 0.05 was considered statistically significant.

3. RESULTS

Until October 2018, 502 subjects who were over 65 years old including 270 (53.8%) men and 232 women were recruited in this study (Table 1). The average age of the sample group was 77.65 ± 5.34 years. According to the value of baPWV, we divided the geriatric patients into low arterial stiffness (baPWV <20 m/s, n = 254) group and high arterial stiffness (baPWV >20 m/s, n = 248) group. Compared to participants with low arterial stiffness, participants with high arterial stiffness were older (p = 0.006) and had higher level of Cat L (p = 0.002), SBP (p = 0.018), pulse pressure (p = 0.017) and Log-CRP level (p = 0.023).

Characteristics	Total (n = 502)	LAF (n = 254)	HAF (n = 248)	p-value
Age (years)	77.65 ± 5.34	74.27 ± 5.27	81.06 ± 5.06	0.006^*
Body mass index (kg/m²)	23.78 ± 3.53	24.32 ± 3.94	23.22 ± 2.98	0.052
SBP (mmHg)	140.19 ± 17.12	132.64 ± 18.13	147.74 ± 16.15	0.018^*
DBP (mmHg)	73.75 ± 7.48	71.95 ± 7.68	74.85 ± 7.38	0.058
Pulse pressure (mmHg)	67.64 ± 9.64	61.69 ± 11.45	72.89 ± 9.73	0.017^*
Glucose (mg/dL)	100.8 ± 26.64	97.74 ± 23.04	103.86 ± 29.88	0.139
Total cholesterol (mg/dL)	156.57 ± 37.90	163.61 ± 43.50	149.46 ± 30.0	0.056
Triglycerides (mg/dL)	108.62 ± 64.64	113.60 ± 70.84	102.45 ± 57.55	0.078
Creatinine (mg/dL)	1.01 ± 0.35	1.00 ± 0.35	1.02 ± 0.36	0.947
Log C-reactive protein (mg/dL)	0.46 ± 0.53	0.40 ± 0.47	0.52 ± 0.57	0.023^*
Cathepsin S (ng/mL)	3.41 ± 0.72	3.25 ± 0.81	3.56 ± 0.53	0.142
Cathepsin V (ng/mL)	0.91 ± 0.24	0.90 ± 0.36	0.92 ± 0.18	0.236
Cathepsin L (pg/mL)	187.20 ± 44.21	160.10 ± 42.36	214.4 ± 46.06	0.002^*
Cathepsin K (pmol/L)	107.4 ± 53.7	106.8 ± 51.9	109.5 ± 51.5	0.426
baPWV (m/s)	20.85 ± 5.49	16.79 ± 2.16	25.00 ± 4.69	<0.001^*

*

p < 0.05 is considered statistically significant.

Values were given as means ± SD and tested by Student’s t-test; Data of C-reactive protein showed skewed distribution and therefore was log-transformed before analysis. LAF, low arterial stiffness; HAF, high arterial stiffness; baPWV, brachial-ankle pulse wave velocity; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Table 1

Clinical variables of 502 geriatric patients with low or high arterial stiffness

Comorbidity and the use of antihypertensives and anti-lipid drugs were presented in Table 2. The medical histories of the geriatric patients included diabetes (33.5%, n = 168), dyslipidemia (32.4%, n = 163), CHD (27.5%, n = 138) and hypertension (45.4%, n = 228). The medications prescribed to the geriatric patients included Angiotensin Receptor Blocker (ARB; 29.6%, n = 149), Angiotensin Converting Enzyme Inhibitor (ACEI; 13.5%, n = 68), Calcium Channel Blockers (CCB; 41.4%, n = 208), β-blocker (31.3%, n = 157), aspirin (22.5%, n = 113) and statins (14.3%, n = 72). Participants in high arterial stiffness group had a higher prevalence of CHD (p = 0.037) and hypertension (p = 0.020). There were not significant differences in subgroup analysis for gender, medical use of aspirin, β-blockers, ACEI, statins, ARB or CCB.

Characteristics	LAF (%)	HAF (%)	p-value
Gender
Female	118 (46.3)	114 (46.1)	0.987
Male	136 (53.7)	134 (53.9)	0.987
Diabetes
No	178 (70.2)	156 (62.9)	0.068
Yes	76 (29.8)	92 (37.1)	0.068
Hypertension
No	177 (69.7)	97 (39.3)	0.020^*
Yes	77 (30.3)	151 (60.7)	0.020^*
Coronary heart disease
No	197 (77.6)	167 (67.3)	0.037^*
Yes	57 (22.4)	81 (32.7)	0.037^*
Dyslipidemia
No	183 (72.1)	156 (62.9)	0.159
Yes	71 (27.9)	92 (37.1)	0.159
Aspirin use
No	200 (78.7)	189 (76.2)	0.068
Yes	54 (21.3)	59 (23.8)	0.068
ARB use
No	203 (80.0)	150 (60.6)	0.108
Yes	51 (20.0)	98 (39.4)	0.108
β-Blocker use
No	204 (80.1)	142 (57.1)	0.060
Yes	51 (19.9)	106 (42.9)	0.060
CCB use
No	161 (63.3)	133 (53.6)	0.451
Yes	93 (36.7)	115 (46.4)	0.451
Statin use
No	227 (89.4)	203 (82.0)	0.390
Yes	27 (10.6)	45 (18.0)	0.390
ACEI use
No	230 (90.5)	204 (82.1)	0.381
Yes	24 (9.5)	44 (17.9)	0.381

*

p < 0.05 is considered statistically significant.

Data are expressed as n (%) of old adults with low or high arterial stiffness and analysis was done using the Chi-square test. LAF, low arterial stiffness; HAF, high arterial stiffness; ARB, Angiotensin receptor blockers; CCB, Calcium channel blockers; ACEI, angiotensin-converting enzyme inhibitor.

Table 2

Distribution of 502 geriatric patients with low or high arterial stiffness in subgroup analysis

The correlation analysis of clinical variables and arterial stiffness in geriatric patients was presented in Table 3. Univariate linear regression analyses revealed that age (r = 0.247; p = 0.028), plasma Cat L level (r = 0.275; p = 0.016), SBP (r = 0.264; p = 0.02), pulse pressure (r = 0.270; p = 0.018) and Log-CRP (r = 0.223; p = 0.039) were positively correlated with baPWV value among the geriatric patients. The multivariate, forward stepwise regression analysis shows that Cat L (β = 0.418, adjusted R² change = 0.154, p = 0.011) and hypertension (β = 0.217, adjusted R² change = 0.092, p = 0.029) were independent factors of the baPWV value in the elderly patients (Table 4).

Variables	r	p-value
Age (years)	0.247	0.028^*
Body mass index (kg/m²)	0.062	0.433
Systolic blood pressure (mmHg)	0.264	0.020^*
Diastolic blood pressure (mmHg)	0.062	0.433
Pulse pressure (mmHg)	0.270	0.018^*
Total cholesterol (mg/dL)	−0.088	0.259
Triglycerides (mg/dL)	−0.004	0.961
Glucose (mg/dL)	0.868	0.606
Log-C-reactive protein (mg/dL)	0.223	0.039^*
Cathepsin S (ng/mL)	0.178	0.151
Cathepsin V (ng/mL)	0.019	0.866
Cathepsin K (pmol/L)	−0.168	0.143
Cathepsin L (pg/mL)	0.275	0.016^*
Creatinine (mg/dL)	0.103	0.185

*

p < 0.05 is considered statistically significant.

Data of C-reactive protein showed skewed distribution and therefore was log-transformed before analysis.

Table 3

Correlation of clinical variables and brachial-ankle pulse wave velocity in univariate linear regression analysis among the 502 geriatric patients

Items	β	Adjusted R²	Adjusted R² change	p-value
Cathepsin L (pg/mL)	0.418	0.154	0.154	0.011^*
Hypertension	0.217	0.319	0.092	0.029^*

*

p < 0.05 was considered statistically significant.

Analysis was done using multivariate logistic regression analysis (adopted factors: hypertension, age, systolic blood pressure, log C-reactive protein, coronary heart disease, pulse pressure and cathepsin L).

Table 4

Multivariate forward stepwise regression analysis of the factors correlated with brachial-ankle pulse wave velocity among 502 geriatric patients

Adjustment of the factors significantly associated with arterial stiffness (adopted factors: CHD, hypertension, pulse pressure, age, Log-CRP and Cat L) in multivariate logistic regression analysis showed that elevated plasma Cat L level [odds ratio (OR): 1.048; 95% confidence interval (CI): 1.043–1.169; p = 0.018), age (OR: 1.054; 95% CI: 1.011–1.039; p = 0.021), and pulse pressure (OR: 1.067; 95% CI: 1.023–1.229; p = 0.038) were independent factors of arterial stiffness among the elderly patients (Table 5).

Variables	OR (95% CI)	p-value
Age (years) (each increase of 1 year)	1.054 (1.011–1.039)	0.021^*
Pulse pressure (mmHg) (each increase of 1 mmHg)	1.067 (1.023–1.229)	0.038^*
Cathepsin L (pg/mL) (each increase of 1 pg/mL)	1.048 (1.043–1.169)	0.018^*

*

p < 0.05 was considered statistically significant.

Analysis was done using multivariate logistic regression analysis (adopted factors: hypertension, age, systolic blood pressure, log C-reactive protein, coronary heart disease, pulse pressure and cathepsin L). OR, odds ratio; CI, confidence interval.

Table 5

Multivariate logistic regression analysis of the factors correlated with brachial-ankle pulse wave velocity among 502 geriatric patients

4. DISCUSSION

This study reported that the plasma Cat L level was positively associated with arterial stiffness and was an independent factor of the baPWV value in geriatric patients. Arterial stiffness is recognized as a surrogate end point for CVD and characterized by a thickening and loss of elasticity of the arterial wall. The increased macrophage apoptosis and matrix degradation by lysosomal enzymes such as cathepsins may play important roles in atheroma [14]. Cathepsins was one of major protease systems expressed in the arteries [15]. Vascular cells such as vascular endothelium, and smooth muscles are important sources of Cat L [16]. Cat L promotes vascular intimal hyperplasia after arterial injury [17]. Hypertension, the most potent risk factor for CVD, can drive pathologic remodeling of the macro-and microcirculation. Previous research showed that Cat L catalyzes the formation of peptides that influence blood pressure and was involved in the autophagy of hypertensive and atherosclerosis [18–20]. Moreover, Cat L is shear-sensitive and upregulated during vascular remodeling [21]. Under the influence of inflammation, the vascular wall may secrete Cat L into the circulation due to oscillatory vortex flows in multiple branches, narrows during cardiac systolic and diastolic process and result in elevated plasma Cat L. In previous research, Cat L have been investigated as biomarkers for CVD [10,14,16,22]. The results of the present study also showed that plasma Cat L level was positively associated with arterial stiffness and was an independent factor for the baPWV value in geriatric patients.

Cardiovascular disease is the leading cause of death in many developed countries. Large elastic artery stiffening is an independent predictor of future CVD diagnosis and likely are responsible for the development of CVD in older adults [23,24]. Arterial hypertension is a common disease with great harm. The risk of hypertension after 55 years old was 90% [25]. Advanced age promotes greater elastic arteriosclerosis, leading to a gradual increase in pulse pressure [26]. Our results noted higher prevalence of hypertension, CHD, elevated SBP and elevated pulse pressure in the high arterial stiffness group. Moreover, age and pulse pressure were an independent factor for the baPWV value after multivariate adjustment.

Inflammation is a major feature in the initiation and progression of atherosclerosis and subsequent CVD [27]. High sensitivity CRP is well-validated, inexpensive, and widely available inflammatory marker [28]. Some researches had showed that CRP is associated with arterial stiffness in a cohort of African-American and white women transitioning through menopause and even in healthy individuals [29,30]. The current study also revealed a correlation between CRP levels and baPWV value in a univariate linear regression analysis. But this correlation did not remain after multivariate adjustment.

There are a few limitations in our study. First, since our study participants were elderly patients from a few medical centers at Southern Shanghai, and further assessment is needed to determine whether the results are applicable to other populations. Second, the study was an across-sectional design, which may affect the statistical significance. Further long-term prospective studies are needed to confirm the relationship between arterial stiffness and Cat L level.

In conclusion, our results demonstrated that higher Cat L plasma level was associated with arterial stiffness in geriatric patients. Moreover, age and pulse pressure were also positively associated with the baPWV value in these geriatric patients.

CONFLICTS OF INTEREST

The authors declare they have no conflicts of interest.

AUTHOR CONTRIBUTIONS

GXF did study conceptualization and wrote (review and editing) the manuscript. CCX and FFP did the data curation. CCX, FFP and JX did the formal analysis and writing (original draft). Project administration and supervision were carried out by TJH and YZ.

FUNDING

This work was supported by the National Natural Science Fund [grant number 81871092] and Shanghai Shen Kang Hospital Development Center Clinical Research Training Project [grant number SHDC12017X21].

Footnotes

Peer review under responsibility of the Association for Research into Arterial Structure and Physiology

Data availability statement: The data used to support the findings of this study are included within the article.

REFERENCES

[1]Z Ungvari, G Kaley, R de Cabo, WE Sonntag, and A Csiszar, Mechanisms of vascular aging: new perspectives, J Gerontol A Biol Sci Med Sci, Vol. 65, 2010, pp. 1028-41.

[2]A Yamashina, H Tomiyama, K Takeda, H Tsuda, T Arai, K Hirose, et al., Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement, Hypertens Res, Vol. 25, 2002, pp. 359-64.

[3]Y Yang, F Fan, M Kou, Y Yang, G Cheng, J Jia, et al., Brachial-ankle pulse wave velocity is associated with the risk of new carotid plaque formation: data from a chinese community-based cohort, Sci Rep, Vol. 8, 2018, pp. 7037.

[4]HA Chapman, RJ Riese, and GP Shi, Emerging roles for cysteine proteases in human biology, Annu Rev Physiol, Vol. 59, 1997, pp. 63-88.

[5]S Helske, S Syväranta, KA Lindstedt, J Lappalainen, K Oörni, MI Mäyränpää, et al., Increased expression of elastolytic cathepsins S, K, and V and their inhibitor cystatin C in stenotic aortic valves, Arterioscler Thromb Vasc Biol, Vol. 26, 2006, pp. 1791-8.

[6]MK Streubel, J Bischof, R Weiss, J Duschl, W Liedl, H Wimmer, et al., Behead and live long or the tale of cathepsin L, Yeast, Vol. 35, 2018, pp. 237-49.

[7]S Chen, Z Wang, L Zhang, G Lu, C Zhou, DW Wang, et al., Association between polymorphism in the human cathepsin L (CTSL1) promoter with hypertension in the Uygur, Kazak and Han populations in China, J Coll Physicians Surg Pak, Vol. 25, 2015, pp. 640-3.

[8]Y Zhong, J Zhao, YJ Gu, YF Zhao, YW Zhou, and GX Fu, Differential levels of cathepsin B and L in serum between young and aged healthy people and their association with matrix metalloproteinase 2, Arch Gerontol Geriatr, Vol. 61, 2015, pp. 285-8.

[9]A Wyczałkowska-Tomasik and L Pączek, Cathepsin B and L activity in the serum during the human aging process: cathepsin B and L in aging, Arch Gerontol Geriatr, Vol. 55, 2012, pp. 735-8.

[10]T Feldreich, AC Carlsson, U Risérus, A Larsson, L Lind, and J Ärnlöv, The association between serum cathepsin L and mortality in older adults, Atherosclerosis, Vol. 254, 2016, pp. 109-16.

[11]KGMM Alberti, RH Eckel, SM Grundy, PZ Zimmet, JI Cleeman, KA Donato, et al., Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity, Circulation, Vol. 120, 2009, pp. 1640-5.

[12]S Kutkiene, Z Petrulioniene, A Laucevicius, P Serpytis, V Kasiulevicius, J Staigyte, et al., Cardiovascular risk assessment of dyslipidemic middle-aged adults without overt cardiovascular disease over the period of 2009–2016 in Lithuania, Lipids Health Dis, Vol. 17, 2018, pp. 233.

[13]Y Zhong, AF Chen, J Zhao, YJ Gu, and GX Fu, Serum levels of cathepsin D, sirtuin1, and endothelial nitric oxide synthase are correlatively reduced in elderly healthy people, Aging Clin Exp Res, Vol. 28, 2016, pp. 641-5.

[14]W Li and XM Yuan, Increased expression and translocation of lysosomal cathepsins contribute to macrophage apoptosis in atherogenesis, Ann N Y Acad Sci, Vol. 1030, 2004, pp. 427-33.

[15]JM Ruddy, AW Akerman, D Kimbrough, EK Nadeau, RE Stroud, R Mukherjee, et al., Differential hypertensive protease expression in the thoracic versus abdominal aorta, J Vasc Surg, Vol. 66, 2017, pp. 1543-52.

[16]J Liu, GK Sukhova, JT Yang, J Sun, L Ma, A Ren, et al., Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells, Atherosclerosis, Vol. 184, 2006, pp. 302-11.

[17]J Cai, H Zhong, J Wu, RF Chen, H Yang, Y Al-Abed, et al., Cathepsin L promotes vascular intimal hyperplasia after arterial injury, Mol Med, Vol. 23, 2017, pp. 92-100.

[18]D Bloemberg, E McDonald, D Dulay, and J Quadrilatero, Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats, Acta Physiol (Oxf), Vol. 210, 2014, pp. 381-91.

[19]M Sun, X Tian, Y Liu, N Zhu, Y Li, G Yang, et al., Cellular repressor of E1A-stimulated genes inhibits inflammation to decrease atherosclerosis in ApoE−/− mice, J Mol Cell Cardiol, Vol. 86, 2015, pp. 32-41.

[20]DFD Mahmood, I Jguirim-Souissi, EH Khadija, N Blondeau, V Diderot, S Amrani, et al., Peroxisome proliferator-activated receptor gamma induces apoptosis and inhibits autophagy of human monocyte-derived macrophages via induction of cathepsin L: potential role in atherosclerosis, J Biol Chem, Vol. 286, 2011, pp. 28858-66.

[21]MO Platt, RF Ankeny, and H Jo, Laminar shear stress inhibits cathepsin L activity in endothelial cells, Arterioscler Thromb Vasc Biol, Vol. 26, 2006, pp. 1784-90.

[22]Y Liu, X Li, D Peng, Z Tan, H Liu, Y Qing, et al., Usefulness of serum cathepsin L as an independent biomarker in patients with coronary heart disease, Am J Cardiol, Vol. 103, 2009, pp. 476-81.

[23]AJ Donato, DR Machin, and LA Lesniewski, Mechanisms of dysfunction in the aging vasculature and role in age-related disease, Circ Res, Vol. 123, 2018, pp. 825-48.

[24]M Wang, RE Monticone, and KR McGraw, Proinflammatory arterial stiffness syndrome: a signature of large arterial aging, J Vasc Res, Vol. 55, 2018, pp. 210-23.

[25]J Gąsowski, K Piotrowicz, and FH Messerli, Arterial hypertension after age 65: from epidemiology and pathophysiology to therapy Do we know where we stand?, Kardiol Pol, Vol. 76, 2018, pp. 723-30.

[26]N Thorin-Trescases and E Thorin, Lifelong cyclic mechanical strain promotes large elastic artery stiffening: increased pulse pressure and old age-related organ failure, Can J Cardiol, Vol. 32, 2016, pp. 624-33.

[27]P Libby, Inflammation in atherosclerosis, Nature, Vol. 420, 2002, pp. 868-74.

[28]TA Pearson, GA Mensah, RW Alexander, JL Anderson, RO Cannon, M Criqui, et al., Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association, Circulation, Vol. 107, 2003, pp. 499-511.

[29]GA Woodard, VG Mehta, RH Mackey, P Tepper, SF Kelsey, AB Newman, et al., C-reactive protein is associated with aortic stiffness in a cohort of African American and white women transitioning through menopause, Menopause, Vol. 18, 2011, pp. 1291-7.

[30]Yasmin, CM McEniery, S Wallace, IS Mackenzie, JR Cockcroft, and IB Wilkinson, C-reactive protein is associated with arterial stiffness in apparently healthy individuals, Arterioscler Thromb Vasc Biol, Vol. 24, 2004, pp. 969-74.

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Journal: Artery Research
Volume-Issue: 25 - 1-2
Pages: 65 - 69
Publication Date: 2019/12/04
ISSN (Online): 1876-4401
ISSN (Print): 1872-9312
DOI: 10.2991/artres.k.191125.001 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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ris enw bib

TY  - JOUR
AU  - Jun Xu
AU  - Feng-Feng Pan
AU  - Chan-Chan Xu
AU  - Yuan Zhong
AU  - Ting-Jun Hu
AU  - Guo-Xiang Fu
PY  - 2019
DA  - 2019/12/04
TI  - Plasma Cathepsin L Level is Positively Associated with Arterial Stiffness in Geriatric Patients
JO  - Artery Research
SP  - 65
EP  - 69
VL  - 25
IS  - 1-2
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191125.001
DO  - 10.2991/artres.k.191125.001
ID  - Xu2019
ER  -

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