Skip to main content

Advertisement

SpringerLink
Log in

The effect of angiotensin-converting enzyme inhibition on inflammatory and angiogenic factors in hypercholesterolemia

  • Original research article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Renin-angiotensin system (RAS) can be activated during hyperlipidemia. Angiotensin II increases the migration of monocytes, cytokine levels, and gene expressions of VEGF and VCAM-1. With this in mind, the present work attempted to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on VEGF, VCAM-1, and nitric oxide (NO) serum levels in hypercholesterolemic rats.

Methods

Forty male Wistar rats were divided into 4 groups including normal diet + saline injection (control), hypercholesterol diet + saline injection, normal diet + captopril injection, and hypercholesterol diet + captopril injection. Before and after the beginning of the diet and after the treatment, the serum levels of cholesterol, triglycerides, LDL, HDL, and NO were measured. Finally, gene expressions of VCAM-1 and VEGF in the vascular cells from aorta were determined.

Results

Hypercholesterolemic diet increased the serum levels of cholesterol, LDL (p < 0.001), triglycerides (p < 0.01) and decreased HDL (p < 0.001). Captopril caused a reduction in the serum levels of cholesterol, LDL (p < 0.001), and triglycerides (p < 0.05) as well as an increase in HDL levels (p < 0.01). Although the serum levels of NO decreased after hypercholesterolemic diet (p < 0.001), no significant change was observed after the treatment. Increased gene expressions of VEGF (p < 0.05) and VCAM-1 (p < 0.01) in hypercholesterolemia were regressed in captopril treated rats (p < 0.01 and p < 0.05, respectively).

Conclusion

Captopril, an ACE inhibitor, improves hyperlipidemia and prevents from overexpression of genes for VEGF and VCAM-1, that are implicated in the inflammation and angiogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. van Rooy MJ, Pretorius E. Obesity, hypertension and hypercholesterolemia as risk factors for atherosclerosis leading to ischemic events. Curr Med Chem 2014;21(19):2121–9.

    Article  Google Scholar 

  2. Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 2011;17(11):1410–22.

    Article  CAS  Google Scholar 

  3. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011;473(7347):317–25.

    Article  CAS  Google Scholar 

  4. Ratheesh M, Shyni GL, Sindhu G, Helen A. Inhibitory effect of Ruta graveolens L. on oxidative damage, inflammation and aortic pathology in hypercholesteromic rats. Exp Toxicol Pathol 2011;63(3):285–90.

    CAS  PubMed  Google Scholar 

  5. Durante A, Peretto G, Laricchia A, Ancona F, Spartera M, Mangieri A, et al. Role of the renin–angiotensin–aldosterone system in the pathogenesis of atherosclerosis. Curr Pharm Des 2012;18(7):981–1004.

    Article  CAS  Google Scholar 

  6. Lu H, Balakrishnan A, Howatt DA, Wu C, Charnigo R, Liau G, et al. Comparative effects of different modes of renin angiotensin system inhibition on hypercholesterolaemia-induced atherosclerosis. Br J Pharmacol 2012;165(6):2000–8.

    Article  CAS  Google Scholar 

  7. Kamper M, Tsimpoukidi O, Chatzigeorgiou A, Lymberi M, Kamper EF. The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats. Transl Res 2010;156(1):26–36.

    Article  CAS  Google Scholar 

  8. Botham KM, Wheeler-Jones CP. Postprandial lipoproteins and the molecular regulation of vascular homeostasis. Prog Lipid Res 2013;52(4):446–64.

    Article  CAS  Google Scholar 

  9. Haghjooyjavanmard S, Nematbakhsh M, Soleimani M. The effect of hypercholesterolemia on serum vascular endothelial growth factor and nitrite concentrations in early stage of atherosclerosis in rabbits. Pak J Nutr 2009;8(1):86–9.

    Article  CAS  Google Scholar 

  10. Sata M, Fukuda D. Crucial role of renin–angiotensin system in the pathogenesis of atherosclerosis. J Med Invest 2010;57(1–2):12–25.

    Article  Google Scholar 

  11. Matsumoto S, Shimabukuro M, Fukuda D, Soeki T, Yamakawa K, Masuzaki H, et al. Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser(1177)/Thr(497) of endothelial nitric oxide synthase in diabetic mice. Cardiovasc Diabetol 2014;13:30.

    Article  Google Scholar 

  12. Forstermann U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch 2010;459(6):923–39.

    Article  Google Scholar 

  13. Conti V, Russomanno G, Corbi G, Izzo V, Vecchione C, Filippelli A. Adrenoreceptors and nitric oxide in the cardiovascular system. Front Physiol 2013;4:321.

    Article  Google Scholar 

  14. Papademetriou V. Inhibition of the renin–angiotensin–aldosterone system to prevent ischemic and atherothrombotic events. Am Heart J 2009;157(6 Suppl.):S24–30.

    Article  CAS  Google Scholar 

  15. Hong Y, Hui SC, Chan TY, Hou JY. Effect of berberine on regression of pressureoverload induced cardiac hypertrophy in rats. Am J Chin Med 2002;30(4):589–99.

    Article  CAS  Google Scholar 

  16. Miguel M, Lopez-Fandino R, Ramos M, Aleixandre A. Short-term effect of eggwhite hydrolysate products on the arterial blood pressure of hypertensive rats. Br J Nutr 2005;94(5):731–7.

    Article  CAS  Google Scholar 

  17. Shen XC, Qian ZY. Effects of crocetin on antioxidant enzymatic activities in cardiac hypertrophy induced by norepinephrine in rats. Pharmazie 2006;61(4):348–52.

    CAS  PubMed  Google Scholar 

  18. Bassaneze V, Barauna VG, Lavini-Ramos C, Kalil J, Schettert IT, Miyakawa AA, et al. Shear stress induces nitric oxide-mediated vascular endothelial growth factor production in human adipose tissue mesenchymal stem cells. Stem Cells Dev 2010;19(3):371–8.

    Article  CAS  Google Scholar 

  19. Peters S. Inhibition of atherosclerosis by angiotensin II type 1 receptor antagonists. Am J Cardiovasc Drugs 2013;13(4):221–4.

    Article  Google Scholar 

  20. Abd Alla J, Langer A, Elzahwy SS, Arman-Kalcek G, Streichert T, Quitterer U. Angiotensin-converting enzyme inhibition down-regulates the pro-atherogenic chemokine receptor 9 (CCR9)-chemokine ligand 25 (CCL25) axis. J Biol Chem 2010;285(30):23496–505.

    Article  CAS  Google Scholar 

  21. Priestley JR, Buelow MW, McEwen ST, Weinberg BD, Delaney M, Balus SF, et al. Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles. Microvasc Res 2013;89: 34–45.

    Article  Google Scholar 

  22. Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol Life Sci 2013;70(16):2859–72.

    Article  CAS  Google Scholar 

  23. Imanishi T, Ikejima H, Tsujioka H, Kuroi A, Kobayashi K, Muragaki Y, et al. Addition of eplerenone to an angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Hypertension 2008;51(3):734–41.

    Article  CAS  Google Scholar 

  24. Heinonen SE, Kivela AM, Huusko J, Dijkstra MH, Gurzeler E, Makinen PI, et al. The effects of VEGF-A on atherosclerosis, lipoprotein profile, and lipoprotein lipase in hyperlipidaemic mouse models. Cardiovasc Res 2013;99(4):716–23.

    Article  CAS  Google Scholar 

  25. Zheng Z, Chen H, Ke G, Fan Y, Zou H, Sun X, et al. Protective effect of perindopril on diabetic retinopathy is associated with decreased vascular endothelial growth factor-to-pigment epithelium-derived factor ratio: involvement of a mitochondria-reactive oxygen species pathway. Diabetes 2009;58(4):954–64.

    Article  CAS  Google Scholar 

  26. Flammer AJ, Sudano I, Hermann F, Gay S, Forster A, Neidhart M, et al. Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis. Circulation 2008;117(17):2262–9.

    Article  CAS  Google Scholar 

  27. Lee YJ, Choi DH, Kim EJ, Kim HY, Kwon TO, Kang DG, et al. Hypotensive, hypolipidemic, and vascular protective effects of Morus alba L. in rats fed an atherogenic diet. Am J Chin Med 2011;39(1):39–52.

    Article  CAS  Google Scholar 

  28. Rathouska J, Nemeckova I, Zemankova L, Strasky Z, Jezkova K, Varejckova M, et al. Cell adhesion molecules and eNOS expression in aorta of normocholesterolemic mice with different predispositions to atherosclerosis. Heart Vessels 2014;1–8.

  29. Lin HL, Yen HW, Hsieh SL, An LM, Shen KP. Low-dose aspirin ameliorated hyperlipidemia, adhesion molecule, and chemokine production induced by high-fat diet in Sprague–Dawley rats. Drug Dev Res 2014;75(2):97–106.

    Article  CAS  Google Scholar 

  30. Zhang F, Ren J, Chan K, Chen H. Angiotensin-(1–7) regulates angiotensin II-induced VCAM-1 expression on vascular endothelial cells. Biochem Biophys Res Commun 2013;430(2):642–6.

    Article  CAS  Google Scholar 

  31. Tsuneki H, Tokai E, Suzuki T, Seki T, Okubo K, Wada T, et al. Protective effects of coenzyme Q10 against angiotensin II-induced oxidative stress in human umbilical vein endothelial cells. Eur J Pharmacol 2013;701(1–3):218–27.

    Article  CAS  Google Scholar 

  32. Montecucco F, Pende A, Mach F. The renin–angiotensin system modulates inflammatory processes in atherosclerosis: evidence from basic research and clinical studies. Mediat Inflamm 2009;2009:752406.

    Article  Google Scholar 

  33. Lu Y, Zhu X, Liang GX, Cui RR, Liu Y, Wu SS, et al. Apelin-APJ induces ICAM-1, VCAM-1 and MCP-1 expression via NF-kappaB/JNK signal pathway in human umbilical vein endothelial cells. Amino Acids 2012;43(5):2125–36.

    Article  CAS  Google Scholar 

  34. Yan SH, Zhao NW, Zhu XX, Wang Q, Wang HD, Fu R, et al. Benazepril inhibited the NF-kappaB and TGF-beta networking on LV hypertrophy in rats. Immunol Lett 2013;152(2):126–34.

    Article  CAS  Google Scholar 

  35. Pasini AF, Garbin U, Nava MC, Stranieri C, Pellegrini M, Boccioletti V, et al. Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients. Am J Hypertens 2007;20(4):443–50.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurogenic Inflammation Research Centre and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Mahmoudabady & Saeed Niazmand

  2. Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Narges Kazemi & Mahmoud Hosseini

  3. Immunology Research Centre, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyyed Abdolrahim Rezaee

  4. Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Soukhtanloo

Authors
  1. Maryam Mahmoudabady
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Narges Kazemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saeed Niazmand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seyyed Abdolrahim Rezaee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Soukhtanloo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mahmoud Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Saeed Niazmand.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahmoudabady, M., Kazemi, N., Niazmand, S. et al. The effect of angiotensin-converting enzyme inhibition on inflammatory and angiogenic factors in hypercholesterolemia. Pharmacol. Rep 67, 837–841 (2015). https://doi.org/10.1016/j.pharep.2015.01.008

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2015.01.008

Keywords

Search

Navigation