Original Articles
16 April 2025
Vol. 3 No. 1 (2025)
Elevated endostatin is associated with hypertension treatment, elevated high sensitivity C-reactive protein, increased waist-hip ratio, and attenuated kidney function, but not with age, in a middle-aged population
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Circulating endostatin has been linked to increased mortality, cardiovascular comorbidities, and renal impairment. However, its role as a cardiovascular risk marker in the general population remains largely unexplored. This study investigates the association between plasma endostatin and atherosclerosis, inflammation, and kidney function in a cohort of 5,026 randomly selected middle-aged individuals from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Plasma levels of endostatin, C-reactive protein (CRP), HbA1c, lipids, and creatinine were analyzed, and their associations with atherosclerosis and related markers were assessed. Coronary artery atherosclerosis was evaluated using coronary computed tomography. Blood pressure, body mass index, and waist circumference were measured, and medication use for diabetes, hyperlipidemia, and hypertension was recorded. Smoking habits were also documented. The following main results were significantly associated with endostatin. Severe coronary atherosclerosis was positively associated in men. Being on hypertensive medication or not, as reported by the participants at the interview at study inclusion, was significantly associated with endostatin. Hypertensive medication increased from 12% to 26% from the lowest to the highest quartile of endostatin. Waist circumference was positively associated, where endostatin increases, on average, 0.21±SD for a 1±SD increase of waist circumference. Kidney function, measured as eGFR, was negatively associated, where endostatin decreases, on average, 0.22±SD for a 1±SD increase in eGFR. Elevated endostatin levels were associated with advanced coronary atherosclerosis in men, antihypertensive treatment, systemic inflammation (increased CRP), increased waist circumference, and impaired kidney function (lower eGFR).
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1. Sasaki T, Fukai N, Mann K, et al. Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin. Embo J 1998;17:4249-56. DOI: https://doi.org/10.1093/emboj/17.15.4249
2. Zatterstrom UK, Felbor U, Fukai N, Olsen BR. Collagen XVIII/endostatin structure and functional role in angiogenesis. Cell Struct Funct 2000;25:97-101. DOI: https://doi.org/10.1247/csf.25.97
3. Folkman J. Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action. Exp Cell Res 2006;312:594-607. DOI: https://doi.org/10.1016/j.yexcr.2005.11.015
4. Li M, Ye C, Feng C, et al. Enhanced antiangiogenic therapy of squamous cell carcinoma by combined endostatin and epidermal growth factor receptor-antisense therapy. Clin Cancer Res 2002;8:3570-8.
5. Mikhailova MM, Volobueva MN, Panteleyev AA. Mechanisms driving the initiation and direction of endothelial sprouting in organotypic co-culture of aorta and spinal cord tissues. Cell Biochem Funct 2021;39:679-87. DOI: https://doi.org/10.1002/cbf.3634
6. Zhong A, Mirzaei Z, Simmons CA. The roles of matrix stiffness and ß-catenin signaling in endothelial-to-mesenchymal transition of aortic valve endothelial cells. Cardiovasc Eng Technol 2018;9:158-67. DOI: https://doi.org/10.1007/s13239-018-0363-0
7. Li XQ, Shang BY, Wang DC, Zhang SH, et al. Endostar, a modified recombinant human endostatin, exhibits synergistic effects with dexamethasone on angiogenesis and hepatoma growth. Cancer Lett 2011;301:212-20. DOI: https://doi.org/10.1016/j.canlet.2010.12.004
8. Borghini A, Manetti M, Nacci F, et al. Systemic sclerosis sera impair angiogenic performance of dermal microvascular endothelial cells: therapeutic implications of cyclophosphamide. PLoS One 2015;10:e0130166. DOI: https://doi.org/10.1371/journal.pone.0130166
9. Kanbay M, Afsar B, Siriopol D, et al. Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival. Eur J Intern Med 2016;33:81-7. DOI: https://doi.org/10.1016/j.ejim.2016.06.033
10. Ruge T, Carlsson AC, Larsson TE, et al. Endostatin level is associated with kidney injury in the elderly: findings from two community-based cohorts. Am J Nephrol 2014;40:417-24. DOI: https://doi.org/10.1159/000369076
11. Chen J, Hamm LL, Kleinpeter MA, et al. Elevated plasma levels of endostatin are associated with chronic kidney disease. Am J Nephrol 2012;35:335-40. DOI: https://doi.org/10.1159/000336109
12. Carlsson AC, Ruge T, Sundström J, et al. Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Hypertension 2013;62:1146-51. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.113.02250
13. Bergström G, Berglund G, Blomberg A, et al. The Swedish CArdioPulmonary BioImage Study: objectives and design. J Intern Med 2015;278:645-59. DOI: https://doi.org/10.1111/joim.12384
14. Nyman U, Grubb A, Larsson A, et al. The revised Lund-Malmö GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population. Clin Chem Lab Med 2014;52:815-24. DOI: https://doi.org/10.1515/cclm-2013-0741
15. Bergström G, Persson M, Adiels M, et al. Prevalence of subclinical coronary artery atherosclerosis in the general population. Circulation 2021;144:916-29. DOI: https://doi.org/10.1161/CIRCULATIONAHA.121.055340
16. George EI, McCulloch RE. Approaches for Bayesian variable selection. Stat Sinica 1997;7:339-73.
17. Wegmann B, Tatemoto P, Miemczyk S, et al. Identification of potentially relevant metals for the etiology of autism by using a Bayesian multivariate approach for partially censored values. Sci Rep 2023;13:12622. DOI: https://doi.org/10.1038/s41598-023-38780-9
18. Bainter SA, McCauley TG, Wager T, Losin EAR. Improving practices for selecting a subset of important predictors in psychology: an application to predicting pain. Adv Methods Pract Psychol Sci 2020;3:66-80. DOI: https://doi.org/10.1177/2515245919885617
19. Kass RE, Raftery AE. Bayes factors. J Am Stat Assoc 1995;90:773-95. DOI: https://doi.org/10.1080/01621459.1995.10476572
20. Zens G, Frühwirth-Schnatter S, Wagner H. Efficient Bayesian modeling of binary and categorical data in R: the UPG package. Available from: https://cran.r-project.org/web/packages/UPG/vignettes/vignette.pdf
21. Neelon B. Bayesian zero-inflated negative binomial regression based on pólya-gamma mixtures. Bayesian Anal 2019;14:829-55. DOI: https://doi.org/10.1214/18-BA1132
22. Panchal VR, Rehman J, Nguyen AT, et al. Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease. J Am Coll Cardiol 2004;43:1383-7. DOI: https://doi.org/10.1016/j.jacc.2003.10.063
23. Mitsuma W, Kodama M, Hanawa H, et al. Serum endostatin in the coronary circulation of patients with coronary heart disease and its relation to coronary collateral formation. Am J Cardiol 2007;99:494-8. DOI: https://doi.org/10.1016/j.amjcard.2006.09.095
24. Liou JY, Shyu KG, Lu MJ, et al. Pericardial fluid and serum levels of vascular endothelial growth factor and endostatin in patients with or without coronary artery disease. J Formos Med Assoc 2006;105:377-83. DOI: https://doi.org/10.1016/S0929-6646(09)60133-9
25. Tian HL, Chen H, Cui YH, et al. Increased protein and mRNA expression of endostatin in the ischemic brain tissue of rabbits after middle cerebral artery occlusion. Neurosci Bull 2007;23:35-40. DOI: https://doi.org/10.1007/s12264-007-0005-2
26. Ren B, Wang Y, Rabasseda X, Wang YZ. Recombinant human endostatin is beneficial to endothelial cell growth exposed to mildly oxidized low-density lipoproteins. Methods Find Exp Clin Pharmacol 2002;24:195-9. DOI: https://doi.org/10.1358/mf.2002.24.4.678450
27. Moulton KS, Heller E, Konerding MA, et al. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999;99:1726-32. DOI: https://doi.org/10.1161/01.CIR.99.13.1726
28. Mao W, Kong J, Dai J, et al. Evaluation of recombinant endostatin in the treatment of atherosclerotic plaques and neovascularization in rabbits. J Zhejiang Univ Sci B 2010;11:599-607. DOI: https://doi.org/10.1631/jzus.B1001011
29. Seppinen L, Pihlajaniemi T. The multiple functions of collagen XVIII in development and disease. Matrix Biol 2011;30:83-92. DOI: https://doi.org/10.1016/j.matbio.2010.11.001
30. Nijhawans P, Behl T, Bhardwaj S. Angiogenesis in obesity. Biomed Pharmacother 2020;126:110103. DOI: https://doi.org/10.1016/j.biopha.2020.110103
31. Kurki E, Shi J, Martonen E, et al. Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice. Nutr Metab (Lond) 2012;9:64. DOI: https://doi.org/10.1186/1743-7075-9-64
32. Li M, Popovic Z, Chu C, et al.Endostatin in renal and cardiovascular diseases. Kidney Dis (Basel) 2021;7:468-81. DOI: https://doi.org/10.1159/000518221
33. Wu Y, Qin J, He J, et al. Serum endostatin is a novel marker for COPD Associated with lower lung function, exacerbation and systemic inflammation. Int J Chron Obstruct Pulmon Dis 2020;15:397-407. DOI: https://doi.org/10.2147/COPD.S234760
34. Moulton KS, Olsen BR, Sonn S, et al. Loss of collagen XVIII enhances neovascularization and vascular permeability in atherosclerosis. Circulation 2004;110:1330-6. DOI: https://doi.org/10.1161/01.CIR.0000140720.79015.3C
35. Xu X, Mao W, Chai Y, et al. Angiogenesis inhibitor, endostar, prevents vasa vasorum neovascularization in a swine atherosclerosis model. J Atheroscler Thromb 2015;22:1100-12. DOI: https://doi.org/10.5551/jat.26906
36. Isobe K, Kuba K, Maejima Y, et al. Inhibition of endostatin/collagen XVIII deteriorates left ventricular remodeling and heart failure in rat myocardial infarction model. Circ J 2010;74:109-19. DOI: https://doi.org/10.1253/circj.CJ-09-0486
37. Alshannag F, Zaki RMM, Hemida E, et al. Endostatin and cystatin C as potential biomarkers for early prediction of preeclampsia. ACS Omega 2023;8:42776-86. DOI: https://doi.org/10.1021/acsomega.3c05586
How to Cite
1.
Larsson A, Wegmann B, Ruge T, Alfredsson J, Östgren CJ, Lindahl T. Elevated endostatin is associated with hypertension treatment, elevated high sensitivity C-reactive protein, increased waist-hip ratio, and attenuated kidney function, but not with age, in a middle-aged population. Global Cardiol [Internet]. 2025 Apr. 16 [cited 2025 Aug. 12];3(1). Available from: https://www.globalcardiology.info/site/article/view/64
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