Interrelationship between circulating vascular еndothelial growth factor-1 and high-sensitive C-reactive protein in stage III arterial hypertension patients


  • A. E. Berezin
  • O. A. Lisovaya



vascular endothelial growth factor-1, high sensitive C-reactive protein, arterial hypertension, ischemic stroke


Introduction. Arterial hypertension is one of the most important causes of mortality in the world. Vascular endothelial growth factor-1 (VEGF-1) pathways are the most frequently involved in hypertension development, especially related cardiovascular remodelling. On the other hand, many retrospective studies have suggested a relationship between cardiovascular risk in antihypertensive patients and VEGF-1. However, an impact of VEGF-1 in hypertensive subjects after ischemic stroke is still uncertain. High sensitive C-reactive protein (hs-CRP) is considered as a sensitive indicator of systemic inflammation and direct mediator of atherogenesis that has been shown to be a powerful predictor of future recurrent coronary and cerebral ischemic events in subjects after stroke. However, the pathogenic and clinical significance of these associations is controversial.

Objective. To evaluate the relationship between circulating vascular endothelial growth factor-1 level and high sensitive C-reactive protein (hs-CRP) in III stage arterial hypertension patients.

Methods. 102 mild-to-moderate arterial hypertension patients were enrolled to the study in 3 weeks after ischemic stroke. Circulating vascular endothelial growth factor-1 level and hs CRP were determined at study entry only.

Results. Analysis of obtained outcomes have been showed that circulating VEGF-1 is independently associated with the hsC-RP (R = 0.478; P = 0.001), type 2 diabetes (R = 0.422; P = 0.001) and hyperlipidemia (R = 0.413; P = 0.002), male gender (R = 0.407; P = 0.001), BMI (R = -0.422; P = 0.001), statins using (R = -0.411; P = 0.001), treatment of ACE inhibitor (R = -0.403; P = 0.001), triglycerides concentration (R = -0.356; P = 0.002). In this case, the circulating VEGF-1 increases non-linearly proportional to the quartiles of the hs CRP quartile level in the blood.

In conclusion, we found that concentration of high-sensitivity C-reactive protein above 10.57 mg/l might be an indicator of vascular endothelial growth factor-1 elevation in hypertensive patients irrespective of traditional cardiovascular risk factors.



Adams H.P. Classifi cation of subtype of acute ischemic stroke: defi nitions for use in a multicenter clinical trial: TOAST: Trial of Org 10172 in Acute Stroke Treatment. / Adams H.P., Bendixen B.H., Kappelle L.J. et al. // Stroke. – 1993. – Vol. 24. – Р. 35–41.

Arenillas J.F. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease / Arenillas J.F., Alvarez-Sabín J., Molina C.A. et al. // Stroke. – 2003. – Vol. 34 (10). – Р. 2463–2468.

Castillo J. Biochemical changes and infl ammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice./ Castillo J., Rodriguez I. // Cerebrovasc Dis. – 2004. – Vol. 17 (suppl 1). – Р. 7–18.

Collin C. The Barthel ADL Index: a reliability study / Collin C., Wade D.T., Davies S., Horne V. // Int Disabil Stud. – 1988. – Vol. 10. – Р. 61–63.

Di Napoli M. Role of C-reactive protein in cerebrovascular disease: a critical review. Expert / Di Napoli M., Elkind M.S., Godoy D.A. et al. // Rev. Cardiovasc Ther. – 2011. – Vol. 9 (12). – Р. 1565–1584.

Ferrara N. The biology of VEGF and its receptors / Ferrara N., Gerber H.P., LeCouter J. // Nat. Med. – 2003. – Vol. 9. – Р. 669–676.

Greenberg D.A. From angiogenesis to neuropathology / Greenberg D.A., Jin K. // Nature. – 2005. – Vol. 438. – Р. 954 959.

Hacke W. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II) / Hacke W., Kaste M., Fieschi C. et al., for the Second European-Australasian Acute Stroke Study Investigators. // Lancet. – 1998. – Vol. 352. – Р. 1245 1251.

Hayashi T. Reduction of ischemic damage by application of vascular endothelial growth factor in rat brain after transient ischemia / Hayashi T., Abe K., Itoyama Y. // J. Cereb Blood Flow Metab. – 1998. – Vol. 18 (8). – Р. 887–895.

Hermann D.M. Implications of vascular endothelial growth factor for postischemic neurovascular remodeling / Hermann D.M., Zechariah A. // J Cereb Blood Flow Metab. – 2009. – Vol. 29. – Р. 1620–1643.

Khurana D. Vascular endothelial growth factor and monocyte chemoattractant protein-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from north India / Khurana D., Mathur D., Prabhakar S. et al. // Front Neurol. – 2013. – Vol. 4. – Р. 27.

Lo E.H. A new penumbra: transitioning from injury into repair after stroke / Lo E.H. // Nat Med. – 2008. – Vol. 14. – Р. 497–500.

Luo Y. Serum CRP concentrations and severity of ischemic stroke subtypes / Luo Y., Wang Z., Li J., Xu Y. // Can. J. Neurol. Sci. – 2012. – Vol. 39 (1). – Р. 69–73.

Luque A. ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165 / Luque A., Carpizo D.R., Iruela-Arispe M.L. // J Biol Chem. – 2003. – Vol. 278. – Р. 23656–23665.

Lyden P.D. A modifi ed National Institutes of Health stroke scale for use in stroke clinical trials. Preliminary reliability and validity / Lyden P.D., Lu M., Levine S. et al. – Stroke. – 2001. – Vol. 32. – Р. 1310–1317.

Merrill M.J. A reassessment of vascular endothelial growth factor in central nervous system pathology / Merrill M.J., Oldfield E.H. // J. Neurosurg. – 2005. – Vol. 103 (5). – Р. 853-868.

Orecchia A. Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the alpha 5 beta 1 integrin. / Orecchia A., Lacal P.M., Schietroma C. et al. // J Cell Sci. – 2003. – Vol. 116. – Р. 3479–3489.

Pagano P.J. The adventitia: The outs and ins of vascular disease / Pagano P.J., Gutterman D.D. // Cardiovasc Res. – 2007. – Vol. 75 (4). – Р. 636–639.

Ridker P.M. C-reactive protein and other markers of infammation in the prediction of cardiovascular disease in women / Ridker P.M., Hennekens C.H., Buring J.E., Rifai N. N. // Engl. J. Med. – 2000. – Vol. 342. – Р. 836–843.

Ridker P.M. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men / Ridker P.M., Paynter N.P., Rifai N. et al. // Circulation. – 2008. – Vol. 118 (22). – Р. 2243–2251.

Ridker P.M. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events / Ridker P.M., Rifai N., Clearfi eld M. et al. // N. Engl. J. Med. – 2001. – Vol. 344. – Р. 1959–1965.

Shen F. Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood-brain barrier and reduces atrophy volume / Shen F., Walker E.J., Jiang L. et al. // J. Cereb. Blood Flow Metab. – 2011. – Vol. 31 (12). – Vol. 2343–2351.

Siow R.C.M. Adventitial growth factor signalling and vascular remodelling: Potential of perivascular gene transfer from the outside-in / Siow R.C.M., Churchman A.T. // Cardiovascular Research. – 2007. – Vol. 75 (4). – Р. 659–668.

Sun Y. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia / Sun Y., Jin K., Xie L., Childs J. et al. // J Clin Invest. – 2003. – Vol. 111. – Р. 1843–1851.

Takahashi H. The vascular endothelial growth factor (VEGF)/ VEGF receptor system and its role under physiological and pathological conditions / Takahashi H., Shibuya M. // Clin. Sci. (Lond). – 2005. – Vol. 109. – Р. 227–241.

Testa U. Vascular endothelial growth factors in cardiovascular medicine / Testa U., Pannitteri G., Condorelli G.L. // J. Cardiovasc Med. – 2008. – Vol. 9. – Р. 1190–1221.

Tuttolomondo A. Infl ammation in Ischemic Stroke Subtypes / Tuttolomondo A., Di Raimondo D., Pecoraro R. et al. // Curr Pharm Des. – 2012. – Vol. 18 (28). – Р. 4289–4310.

Zachary I. Vascular protection: a novel nonangiogenic cardiovascular role for vascular endothelial growth factor / Zachary I., Mathur A., Yla-Herttuala S., Martin J. // Arterioscler Thromb Vasc Biol. – 2000. – Vol. 20. – Р. 1512–1520.

How to Cite

Berezin AE, Lisovaya OA. Interrelationship between circulating vascular еndothelial growth factor-1 and high-sensitive C-reactive protein in stage III arterial hypertension patients. Zaporozhye Medical Journal [Internet]. 2013Nov.13 [cited 2024Jul.17];15(5). Available from:



Original research