Effect of heme oxygenase 1 and renin/prorenin receptor on oxidized low‑density lipoprotein‑induced human umbilical vein endothelial cells

Gong,Xin; Liu,Congyang; Wang,Hongling; Fan,Jinying; Jiang,Cuihong; Zou,Yong

doi:10.3892/etm.2019.7769

Effect of heme oxygenase 1 and renin/prorenin receptor on oxidized low‑density lipoprotein‑induced human umbilical vein endothelial cells

Authors:
- Xin Gong
- Congyang Liu
- Hongling Wang
- Jinying Fan
- Cuihong Jiang
- Yong Zou
View Affiliations

Affiliations: Department of Integrated Chinese and Western Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Central Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Department of Cardiology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
Published online on: July 12, 2019 https://doi.org/10.3892/etm.2019.7769
Pages: 1752-1760
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The incidence of depression has previously been correlated to hypertension. The aim of the present study was to explore the mechanisms of depression and hypertension by examining the expression and interaction of renin/prorenin receptor (PRR) and heme oxygenase 1 (HO‑1) in vascular endothelial cells. A case‑control study was conducted, and general data and serum factors were compared between hypertension patients complicated with depression and patients with hypertension alone. Logistic regression analysis was used to detect risk factors associated with hypertension complicated with depression. In addition, human umbilical vein endothelial cells (HUVECs) were treated with oxidized low‑density lipoprotein (ox‑LDL) and/or PRR gene silencing, and a Cell Counting Kit‑8 (CCK‑8) assay was performed to test their proliferation. The concentrations of inflammatory factors and oxidative stress factor were also detected using enzyme‑linked immunosorbent assay and chemical colorimetry. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction were applied to detect protein and mRNA expression levels, respectively. The results revealed that HO‑1 and renin precursor (Rep) were independent factors that affected hypertension complicated with depression. Serum HO‑1 levels in patients with hypertension complicated with depression were significantly lower than that in hypertensive patients without depression, while Rep levels in patients with hypertension complicated with depression were significantly higher than that in hypertensive patients without depression. In HUVECs, ox‑LDL reduced the cell proliferation in a dose‑dependent manner, upregulated the expression of PRR gene and downregulated the expression of HO‑1 gene. It was also observed that silencing of the PRR gene promoted the expression of the HO‑1 gene. Furthermore, ox‑LDL upregulated the inflammatory response and oxidative stress levels, while PRR gene silencing inhibited the ox‑LDL‑induced inflammatory factor and oxidative stress levels in HUVECs. Thus, regulating the expression levels of HO‑1 and PRR to inhibit the oxidative stress and pro‑inflammatory effect of ox‑LDL may provide new insight for the treatment of hypertension patients with depression.

View Figures

View References

1	Kretchy IA, Owusu-Daaku FT and Danquah SA: Mental health in hypertension: Assessing symptoms of anxiety, depression and stress on anti-hypertensive medication adherence. Int J Ment Health Syst. 8:252014. View Article : Google Scholar : PubMed/NCBI
2	Cene CW, Halladay JR, Gizlice Z, Roedersheimer K, Hinderliter A, Cummings DM, Donahue KE, Perrin AJ and DeWalt DA: Associations between subjective social status and physical and mental health functioning among patients with hypertension. J Health Psychol. 21:2624–2635. 2016. View Article : Google Scholar : PubMed/NCBI
3	Li Z, Li Y, Chen L, Chen P and Hu Y: Prevalence of depression in patients with hypertension: A systematic review and meta-analysis. Medicine (Baltimore). 94:e13172015. View Article : Google Scholar : PubMed/NCBI
4	Almas A, Patel J, Ghori U, Ali A, Edhi AI and Khan MA: Depression is linked to uncontrolled hypertension: A case-control study from Karachi, Pakistan. J Ment Health. 23:292–296. 2014. View Article : Google Scholar : PubMed/NCBI
5	Chen Y, Guo F, Ru Z, Kong H, Sun H, Yu H, Yang W, Zhang Q and Zhou M: Nuclear factor-κB signaling negatively regulates high glucose-induced vascular endothelial cell damage downstream of the extracellular signal-regulated kinase/c-Jun N-terminal kinase pathway. Exp Ther Med. 14:3851–3855. 2017. View Article : Google Scholar : PubMed/NCBI
6	Ando J and Kamiya A: Blood flow and vascular endothelial cell function. Front Med Biol Eng. 5:245–264. 1993.PubMed/NCBI
7	Schulz E, Gori T and Münzel T: Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res. 34:665–673. 2011. View Article : Google Scholar : PubMed/NCBI
8	Dinh QN, Drummond GR, Sobey CG and Chrissobolis S: Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. Biomed Res Int. 2014:4069602014. View Article : Google Scholar : PubMed/NCBI
9	Crowley SD: The cooperative roles of inflammation and oxidative stress in the pathogenesis of hypertension. Antioxid Redox Signal. 20:102–120. 2014. View Article : Google Scholar : PubMed/NCBI
10	Wolkowitz OM, Mellon SH, Epel ES, Lin J, Dhabhar FS, Su Y, Reus VI, Rosser R, Burke HM, Kupferman E, et al: Leukocyte telomere length in major depression: Correlations with chronicity, inflammation and oxidative stress-preliminary findings. PLoS One. 6:e178372011. View Article : Google Scholar : PubMed/NCBI
11	Czarny P, Wigner P, Galecki P and Sliwinski T: The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression. Prog Neuropsychopharmacol Biol Psychiatry. 80:309–321. 2018. View Article : Google Scholar : PubMed/NCBI
12	Carey RM: The intrarenal renin-angiotensin system in hypertension. Adv Chronic Kidney Dis. 22:204–210. 2015. View Article : Google Scholar : PubMed/NCBI
13	Gupta S, Chattopadhyaya I, Agrawal BK, Sehajpal PK and Goel RK: Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to ramipril in patients with essential hypertension. J Postgrad Med. 61:21–26. 2015. View Article : Google Scholar : PubMed/NCBI
14	Murck H, Schussler P and Steiger A: Renin-angiotensin-aldosterone system: The forgotten stress hormone system: Relationship to depression and sleep. Pharmacopsychiatry. 45:83–95. 2012. View Article : Google Scholar : PubMed/NCBI
15	Peng H, Li W, Seth DM, Nair AR, Francis J and Feng Y: (Pro)renin receptor mediates both angiotensin II-dependent and -independent oxidative stress in neuronal cells. PLoS One. 8:e583392013. View Article : Google Scholar : PubMed/NCBI
16	Li W, Liu J, Hammond SL, Tjalkens RB, Saifudeen Z and Feng Y: Angiotensin II regulates brain (pro)renin receptor expression through activation of cAMP response element-binding protein. Am J Physiol Regul Integr Comp Physiol. 309:R138–R147. 2015. View Article : Google Scholar : PubMed/NCBI
17	Shen Y, Yang T, Guo S, Li X, Chen L, Wang T and Wen F: Increased serum ox-LDL levels correlated with lung function, inflammation, and oxidative stress in COPD. Mediators Inflamm. 2013:9723472013. View Article : Google Scholar : PubMed/NCBI
18	Le WD, Xie WJ and Appel SH: Protective role of heme oxygenase-1 in oxidative stress-induced neuronal injury. J Neurosci Res. 56:652–658. 1999. View Article : Google Scholar : PubMed/NCBI
19	Innes K, Hooper J, Bramley M and DahDah P: Creation of a clinical classification. International statistical classification of diseases and related health problems-10th revision, Australian modification (ICD-10-AM). Health Inf Manag. 27:31–38. 1997.PubMed/NCBI
20	Jaffe EA, Nachman RL, Becker CG and Minick CR: Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 52:2745–2756. 1973. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Nguyen G and Danser AH: Prorenin and (pro)renin receptor: A review of available data from in vitro studies and experimental models in rodents. Exp Physiol. 93:557–563. 2008. View Article : Google Scholar : PubMed/NCBI
23	Lee AL, Ogle WO and Sapolsky RM: Stress and depression: Possible links to neuron death in the hippocampus. Bipolar Disord. 4:117–128. 2002. View Article : Google Scholar : PubMed/NCBI
24	Grimsrud A, Stein DJ, Seedat S, Williams D and Myer L: The association between hypertension and depression and anxiety disorders: Results from a nationally-representative sample of South African adults. PLoS One. 4:e55522009. View Article : Google Scholar : PubMed/NCBI
25	Löwe B, Gräfe K, Ufer C, Kroenke K, Grünig E, Herzog W and Borst MM: Anxiety and depression in patients with pulmonary hypertension. Psychosom Med. 66:831–836. 2004. View Article : Google Scholar : PubMed/NCBI
26	Scalco AZ, Scalco MZ, Azul JB and Lotufo Neto F: Hypertension and depression. Clinics (Sao Paulo). 60:241–250. 2005. View Article : Google Scholar : PubMed/NCBI
27	Meng L, Chen D, Yang Y, Zheng Y and Hui R: Depression increases the risk of hypertension incidence: A meta-analysis of prospective cohort studies. J Hypertens. 30:842–851. 2012. View Article : Google Scholar : PubMed/NCBI
28	Robaczewska J, Kedziora-Kornatowska K, Kucharski R, Nowak M, Muszalik M, Kornatowski M and Kędziora J: Decreased expression of heme oxygenase is associated with depressive symptoms and may contribute to depressive and hypertensive comorbidity. Redox Rep. 21:209–218. 2016. View Article : Google Scholar : PubMed/NCBI
29	Zhao Y, Zhang L, Qiao Y, Zhou X, Wu G, Wang L, Peng Y, Dong X, Huang H, Si L, et al: Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy. PLoS One. 8:e759272013. View Article : Google Scholar : PubMed/NCBI
30	Unuma K, Aki T, Matsuda S, Funakoshi T, Yoshida K and Uemura K: Inducer of heme oxygenase-1 cobalt protoporphyrin accelerates autophagy and suppresses oxidative damages during lipopolysaccharide treatment in rat liver. Hepatol Res. 43:91–96. 2013. View Article : Google Scholar : PubMed/NCBI
31	Mendonça L, Mendes-Ferreira P, Bento-Leite A, Cerqueira R, Amorim MJ, Pinho P, Brás-Silva C, Leite-Moreira AF and Castro-Chaves P: Angiotensin-(1–7) modulates angiotensin II-induced vasoconstriction in human mammary artery. Cardiovasc Drugs Ther. 28:513–522. 2014. View Article : Google Scholar : PubMed/NCBI
32	Deng Y, Deng Y, He X, Chu J, Zhou J, Zhang Q, Guo W, Huang P, Guan X, Tang Y, et al: Prenatal inflammation-induced NF-kB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring. Sci Rep. 6:216922016. View Article : Google Scholar : PubMed/NCBI
33	Hu LH, Yu Y, Jin SX, Nie P, Cai ZH, Cui ML, Sun SQ, Xiao H, Shao Q, Shen LH and He B: Orphan nuclear receptor Nur77 Inhibits Oxidized LDL-induced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells. BMC Immunol. 15:542014. View Article : Google Scholar : PubMed/NCBI
34	Liu W, Yin Y, Zhou Z, He M and Dai Y: OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation. Inflamm Res. 63:33–43. 2014. View Article : Google Scholar : PubMed/NCBI
35	Catar RA, Muller G, Heidler J, Schmitz G, Bornstein SR and Morawietz H: Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells. Horm Metab Res. 39:801–805. 2007. View Article : Google Scholar : PubMed/NCBI
36	Ferrario CM and Mullick AE: Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease. Pharmacol Res. 125:57–71. 2017. View Article : Google Scholar : PubMed/NCBI
37	Qiao H, Chen H, Dong Y, Ma H, Zhao G, Tang F and Li Z: Polydatin attenuates H2O2-induced oxidative stress via PKC pathway. Oxid Med Cell Longev. 2016:51394582016. View Article : Google Scholar : PubMed/NCBI
38	Mai J, Qiu Q, Lin YQ, Luo NS, Zhang HF, Wen ZZ, Wang JF and YangXin C: Angiotensin II-derived reactive oxygen species promote angiogenesis in human late endothelial progenitor cells through heme oxygenase-1 via ERK1/2 and AKT/PI3K pathways. Inflammation. 37:858–870. 2014. View Article : Google Scholar : PubMed/NCBI
39	Davis PA, Pagnin E, Dal Maso L, Caielli P, Maiolino G, Fusaro M, Paolo Rossi G and Calò LA: SIRT1, heme oxygenase-1 and NO-mediated vasodilation in a human model of endogenous angiotensin II type 1 receptor antagonism: implications for hypertension. Hypertens Res. 36:873–878. 2013. View Article : Google Scholar : PubMed/NCBI
40	Mancuso C, Santangelo R and Calabrese V: The heme oxygenase/biliverdin reductase system: A potential drug target in Alzheimers disease. J Biol Regul Homeost Agents 27(2 Suppl). 75–87. 2013.
41	Lin HY, Yeh WL, Huang BR, Lin C, Lai CH, Lin H and Lu DY: Desipramine protects neuronal cell death and induces heme oxygenase-1 expression in Mes23.5 dopaminergic neurons. PLoS One. 7:e501382012. View Article : Google Scholar : PubMed/NCBI
42	Zhao CY, Lei H, Zhang Y, Li L, Xu SF, Cai J, Li PP, Wang L, Wang XL and Peng Y: L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating Heme oxygenase-1 in lipopolysaccharide-treated mice. J Asian Nat Prod Res. 18:289–302. 2016. View Article : Google Scholar : PubMed/NCBI
43	Lee DS, Lee M, Sung SH and Jeong GS: Involvement of heme oxygenase-1 induction in the cytoprotective and neuroinflammatory activities of Siegesbeckia Pubescens isolated from 5,3′-dihydroxy-3,7,4′-trimethoxyflavone in HT22 cells and BV2 cells. Int Immunopharmacol. 40:65–72. 2016. View Article : Google Scholar : PubMed/NCBI