title: Renal Denervation Reduces Monocyte Activation and Monocyte-Platelet Aggregate Formation: An Anti-Inflammatory Effect Relevant for Cardiovascular Risk.
abstract: Overactivation of renal sympathetic nervous system and low-grade systemic inflammation are common features of hypertension. Renal denervation (RDN) reduces sympathetic activity in patients with resistant hypertension. However, its effect on systemic inflammation has not been examined. We prospectively investigated the effect of RDN on monocyte activation and inflammation in patients with uncontrolled hypertension scheduled for RDN. Ambulatory blood pressure, monocyte, and monocyte subset activation and inflammatory markers were assessed at baseline, 3 months, and 6 months after procedure in 42 patients. RDN significantly lowered blood pressure at 3 months (150.5±11.2/81.0±11.2 mm Hg to 144.7±11.8/77.9±11.0 mm Hg), which was sustained at 6 months (144.7±13.8/78.6±11.0 mm Hg). Activation status of monocytes significantly decreased at 3 months (P<0.01) and 6 months (P<0.01) after the procedure. In particular, classical monocyte activation was reduced at 6 months (P<0.05). Similarly, we observed a reduction of several inflammatory markers, including monocyte-platelet aggregates (3 months, P<0.01), plasma monocyte chemoattractant protein-1 levels (3 months, P<0.0001; 6 months, P<0.05), interleukin-1β (3 months, P<0.05; 6 months, P<0.05), tumor necrosis factor-α (3 months, P<0.01; 6 months, P<0.05), and interleukin-12 (3 months, P<0.01; 6 months, P<0.05). A positive correlation was observed between muscle sympathetic nerve activity and monocyte activation before and after the procedure. These results indicate that inhibition of sympathetic activity via RDN is associated with a reduction of monocyte activation and other inflammatory markers in hypertensive patients. These findings point to a direct interaction between the inflammatory and sympathetic nervous system, which is of central relevance for the understanding of beneficial cardiovascular effects of RDN.
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Maria T K
authors.initials: MT
authors.lastname: Zaldivia
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rivera
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Dagmara
authors.initials: D
authors.lastname: Hering
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Petra
authors.initials: P
authors.lastname: Marusic
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sata
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Bock
authors.initials: B
authors.lastname: Lim
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Nina
authors.initials: N
authors.lastname: Eikelis
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lee
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Nay M
authors.initials: NM
authors.lastname: Htun
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Duval
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Louise
authors.initials: L
authors.lastname: Hammond
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Steffen U
authors.initials: SU
authors.lastname: Eisenhardt
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Ulrike
authors.initials: U
authors.lastname: Flierl
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.).
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schlaich
authors.affiliation: From the Atherothrombosis and Vascular Biology (M.T.K.Z., J.R., B.L., N.M.H., S.U.E., U.F., K.P.) and Neurovascular Hypertension and Kidney Disease Laboratory (D.H., P.M., Y.S., N.E., R.L., G.W.L., M.D.E., J.D., L.H., M.P.S.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne (M.T.K.Z., N.M.H., M.P.S., K.P.); Dobney Hypertension Centre, School of Medicine and Pharmacology-Royal Perth Hospital Unit, University of Western Australia, Australia (D.H., P.M., M.P.S.); and Department of Plastic and Hand Surgery, University Medical Centre, Freiburg, Germany (S.U.E.). karlheinz.peter@bakeridi.edu.au.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000502:physiology*; D018660:Blood Pressure Monitoring, Ambulatory; D017115:Catheter Ablation; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000601:surgery*; D007668:Kidney / Q000294:innervation*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010974:Platelet Aggregation / Q000502:physiology*; D011446:Prospective Studies; D013562:Sympathectomy / Q000379:methods*; D013997:Time Factors; D055815:Young Adult
keywords: hypertension; inflammation; monocyte activation; renal denervation; sympathetic nervous system