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Soluble vascular endothelial growth factor receptor-1 is reduced in patients with resistant hypertension after renal denervation

Journal of Human Hypertension volume 31, pages 248–252 (2017)Cite this article

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Abstract

Renal denervation (RDN) has been shown in several studies to reduce blood pressure (BP) in patients with resistant hypertension (RH). Data on potential biomarkers associated with BP changes remain scarce. We evaluated whether soluble vascular endothelial growth factor receptor (sVEGFR-1) is affected by the procedure. A total of 57 patients with RH participated in this study. BP and heart rate were recorded at baseline and at 3 months follow-up, at which time blood samples were collected to determine the levels of sVEGFR-1, VEGF-A, VEGF-C, nitric oxide (NO), soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1. None of the biomarkers had a predictive value that could identify responders vs non-responders to RDN. However, sVEGFR-1 concentration was dramatically reduced after RDN (5913±385 vs 280±57 pg ml−1, P<0.001). At the same time VEGF-A levels were significantly increased (10.0±3.0 vs 55.5±7.9 pg ml−1, P<0.001), without significant changes in VEGF-C. NO levels were significantly increased after RDN in the whole group (82.6±6.2 vs 106.9±7.8 μM, P=0.021). Interestingly, the elevation in NO levels at 3 months was only seen in patients who demonstrated a reduction in systolic BP of ⩾10 mm Hg (78.9±8.3 vs 111.6±11.7 μM, P=0.018). We report a significant reduction in sVEGFR-1 levels after RDN procedure, which was accompanied by a significant increase in VEGF-A concentration as well as NO. Changes in plasma cytokines were not quantitatively linked to magnitude of BP reduction. An RDN-induced reduction in sVEGFR-1 plasma levels and increase in VEGF-A would raise the VEGF-A/sVEGFR-1 ratio, thereby increasing VEGF-A bioavailability to act on its full-length receptor and may contribute to the BP-lowering effect potentially via NO-mediated pathways.

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Acknowledgements

We thank the study participants for their time, cooperation and effort. The research described in this paper has been partly supported by the National Health and Medical Research Council of Australia and the Victorian Government’s Operational Infrastructure Support Program.

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Author notes

  1. H Krum: Deceased.

Authors and Affiliations

  1. Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    N Eikelis, D Hering, P Marusic, E A Lambert, Y Sata, G W Lambert, M D Esler & M P Schlaich

  2. School of Medicine and Pharmacology—Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia

    D Hering, P Marusic, M D Esler & M P Schlaich

  3. Heart Centre Alfred Hospital, Melbourne, Victoria, Australia

    A S Walton & M P Schlaich

  4. Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia

    H Krum

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Correspondence to N Eikelis.

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Competing interests

Drs ASW, HK, GWL, MDE and MPS are investigators in studies sponsored by Medtronic. The laboratories of Drs MPS, GWL and MDE currently received research funding from Medtronic. Professor GWL has acted as a consultant for Medtronic and has received honoraria or travel support for presentations from Pfizer, Wyeth Pharmaceuticals, Servier and Medtronic. Professor MDE serves on scientific advisory boards of Abbott (formerly Solvay) Pharmaceuticals and Medtronic. Professor MPS serves on scientific advisory boards for Abbott (formerly Solvay) Pharmaceuticals, BI, Novartis Pharmaceuticals and Medtronic and has received honoraria and travel support from Abbott, BI, Servier, Novartis and Medtronic. The remaining author declares no conflict of interest.

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Eikelis, N., Hering, D., Marusic, P. et al. Soluble vascular endothelial growth factor receptor-1 is reduced in patients with resistant hypertension after renal denervation. J Hum Hypertens 31, 248–252 (2017). https://doi.org/10.1038/jhh.2016.64

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