Soluble vascular endothelial growth factor receptor-1 is reduced in patients with resistant hypertension after renal denervation.
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.
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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Eikelis
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.|School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
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Hering
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.|School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
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Marusic
Heart Centre Alfred Hospital, Melbourne, Victoria, Australia.
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Walton
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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Lambert
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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Sata
Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Krum
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
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Lambert
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.|School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
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Esler
Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.|School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.|Heart Centre Alfred Hospital, Melbourne, Victoria, Australia.
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Schlaich
D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003714:Denervation; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000601:surgery; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007668:Kidney / Q000294:innervation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D015415:Biomarkers; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D040281:Vascular Endothelial Growth Factor Receptor-1