Skip to main content
SpringerLink
Log in

Serum MCP-1 and VEGF Levels are not Affected by Inhibition of the Renin-Angiotensin System in Patients with Acute Myocardial Infarction

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) stimulate angiogenesis in ischemic tissues, and both of their expression are stimulated by angiotensin II. We measured the serum concentrations of MCP-1 and VEGF in patients with acute myocardial infarction (AMI) and investigated the effects of an early administration of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) on their levels. Thirty-six patients with AMI were divided randomly into 3 therapeutic groups; the ACEI perindopril, the ARB candesartan and control (without perindopril and candesartan), and the drugs were administered within 36 hours after the onset of AMI. Peripheral blood mononuclear cells (PBMC) obtained from the patients were incubated for 24 hours. The levels of MCP-1 and VEGF in the serum and the supernatant of PBMC were measured by ELISA. The serum MCP-1 and VEGF levels in AMI patients at the time of admission were not significantly different from those in healthy control subjects, but both MCP-1 and VEGF levels in the patients were increased significantly after 7 days. There was no significant difference in the serum MCP-1 and VEGF levels among the 3 therapeutic groups. The production of MCP-1 and VEGF by PBMC was also increased in AMI patients compared with healthy control subjects, and there was also no difference in their production among the 3 therapeutic groups. In conclusion, circulating MCP-1 and VEGF levels and their production by PBMC are elevated during the course of AMI, and early administration of ACEI and ARB does not affect their levels.

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. Shimpo M, Ikeda U, Maeda Y, et al. AAV-mediated VEGF gene transfer into skeletal muscle stimulates angiogenesis and improves blood flow in a rat hindlimb ischemia model. Cardiovasc Res 2002;53993-1001.

    Google Scholar 

  2. Ito WD, Arras M, Winkler B, et al. Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion. Circ Res 1997;80829-837.

    Google Scholar 

  3. Deindl E, Buschmann I, Hoefer IE, et al. Role of ischemia and of hypoxia-inducible genes in arteriogenesis after femoral artery occlusion in the rabbit. Circ Res 2001;89779-786.

    Google Scholar 

  4. Williams B, Baker AQ, Gallacher B, et al. Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. Hypertension 1995;25913-917.

    Google Scholar 

  5. Funakoshi Y, Ichiki T, Shimokawa H, et al. Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells. Hypertension 2001;38100-1004.

    Google Scholar 

  6. Mclnnes GT. Clinical potential: Angiotensin converting enzyme inhibition or angiotensin II antagonist? J Hypertens 2001;19S61-S67.

    Google Scholar 

  7. Latini R, Maggioni AP, Flather M, et al. ACE inhibitor use in patients with myocardial infarction: Summary of evidence from clinical trials. Circulation 1995;922132-2137.

    Google Scholar 

  8. Soejima H, Ogawa H, Yasue H, et al. Angiotensinconverting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction. J Am Coll Cardiol 1999;34983-988.

    Google Scholar 

  9. Strawn WB, Chappell MC, Dean RH, et al. Inhibition of early atherogenesis by losartan in monkeys with diet-induced hypercholesterolemia. Circulation 2000;1011586-1593.

    Google Scholar 

  10. Sasaki K, MuroharaT, Ikeda H, et al. Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. J Clin Invest 2002;109603-611.

    Google Scholar 

  11. Gilbert RE, Kelly DJ, Cox AJ, et al. Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes. Diabetologia 2000;431360-1367.

    Google Scholar 

  12. Volpert OV, Ward WF, Lingen MW, et al. Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats. J Clin Invest 1996;98671-679.

    Google Scholar 

  13. Wang DH, Prewitt RL. Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats. Hypertension 1990;1568-77.

    Google Scholar 

  14. Cameron NE, Cotter MA, Robertson S. Angiotensin converting enzyme inhibition prevents development of muscle and nerve dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats. Diabetologia 1992;3512-18.

    Google Scholar 

  15. Maxfield EK, Cameron NE, Cotter MA, et al. Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneural angiogenesis in streptozotocin-diabetic rats. Diabetologia 1993;361230-1237.

    Google Scholar 

  16. Olivetti G, Cigola E, Lagrasta C, et al. Spirapril prevents left ventricular hypertrophy, decreases myocardial damage and promotes angiogenesis in spontaneously hypertensive rats. J Cardiovasc Pharmacol 1993;21362-370.

    Google Scholar 

  17. Clozel JP, Kuhn H, Hefti F. Effects of chronic ACE inhibition on cardiac hypertrophy and coronary vascular reserve in spontaneously hypertensive rats with developed hypertension. J Hypertens 1989;7267-275.

    Google Scholar 

  18. Gohlke P, Kuwer I, Schnell A, et al. Blockade of bradykinin B2 receptors prevents the increase in capillary density induced by chronic angiotensin-converting enzyme inhibitor treatment in stroke-prone spontaneously hypertensive rats. Hypertension 1997;29478-482.

    Google Scholar 

  19. Galcera-Tomas J, Castillo-Soria FJ, Villegas-Garcia MM, et al. Effects of early use of atenolol or captopril on infarct size and ventricular volume: A double-blind comparison in patients with anterior acute myocardial infarction. Circulation 2001;103813-819.

    Google Scholar 

  20. de Kam PJ, Voors AA, van den Berg MP, et al. Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: Results of a meta-analysis of 845 patients. FAMIS, CAPTIN and CATS Investigators. J Am Coll Cardiol 2000;362047-2053.

    Google Scholar 

  21. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: Randomized trial-The Losartan Heart Failure Survival Study ELITE II. Lancet 2000;3551582-1587.

  22. Hojo Y, Ikeda U, Zhu Y, et al. Expression of vascular endothelial growth factor in patients with acute myocardial infarction. J Am Coll Cardiol 2000;35968-973.

    Google Scholar 

  23. Hojo Y, Ikeda U, Katsuki T, et al. Chemokine expression in coronary circulation after coronary angioplasty as a prognostic factor for restenosis. Atherosclerosis 2001;156165-170.

    Google Scholar 

  24. Vasan RS, Sullivan LM, Roubenoff R, et al. Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction; The Framingham Heart Study. Circulation 2003;1071486-1491.

    Google Scholar 

  25. Mallory GK, White PD, Salcedo-Salgar J. The speed of healing of myocardial infarction: A study of the pathologic anatomy in seventy-two cases. AmHeart J 1939;18647-671.

    Google Scholar 

  26. Arras M, Ito WD, Scholz D, et al. Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. J Clin Invest 1998;10140-50.

    Google Scholar 

  27. Kakio T, Matsumori A, Ono K, et al. Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart. Lab Invest 2000;801127-1136.

    Google Scholar 

  28. Kumar AG, Ballantyne CM, Michael LH, et al. Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium. Circulation 1997;95693-700.

    Google Scholar 

  29. Seino Y, Ikeda U, Sekiguchi H, et al. Expression of leukocyte chemotactic cytokines in myocardial tissue. Cytokine 1995;7301-304.

    Google Scholar 

  30. Williams B, Baker AQ, Gallacher B, et al. Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. Hypertension 1995;25913-917.

    Google Scholar 

  31. Jilma B, Li-Saw-Hee FL, Wagner OF, et al. Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1. Clin Sci 2002;103131-136.

    Google Scholar 

  32. Matsumori A, Furukawa Y, Hashimoto T, et al. Plasma levels of the monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 are elevated in patients with acute myocardial infarction. J Mol Cell Cardiol 1997;29419-423.

    Google Scholar 

  33. de Lemos JA, Morrow DA, Sabatine MS, et al. Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes. Circulation 2003;107690-695.

    Google Scholar 

  34. Parissis JT, Adamopoulos S, Venetsanou KF, et al. Serum profiles of C-C chemokines in acute myocardial infarction: Possible implication in postinfarction left ventricular remodeling. J Interferon Cytokine Res 2002;22223-229.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, Jichi Medical School, Tochigi

    Yoshiaki Murakami, Kenji Kurosaki, Keiji Matsui, Kazuyuki Shimada & Uichi Ikeda

  2. Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto, Japan

    Uichi Ikeda

Authors
  1. Yoshiaki Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Kurosaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keiji Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuyuki Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Uichi Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murakami, Y., Kurosaki, K., Matsui, K. et al. Serum MCP-1 and VEGF Levels are not Affected by Inhibition of the Renin-Angiotensin System in Patients with Acute Myocardial Infarction. Cardiovasc Drugs Ther 17, 249–255 (2003). https://doi.org/10.1023/A:1026128308440

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026128308440

Search

Navigation