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Published on: May 26, 2022
Angiotensin II receptor blockers decrease serum concentration of fatty acid-binding protein 4 in patients with
Masato Furuhashi1, Tomohiro Mita1, Norihito Moniwa2
1Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Insights
Angiotensin II receptor blockers (ARBs) significantly reduce circulating fatty acid-binding protein 4 (FABP4) levels in hypertensive patients. This class effect of ARBs may contribute to preventing cardiovascular events.
Area of Science:
- Cardiovascular Pharmacology
- Metabolic Syndrome Research
- Adipokine Signaling Pathways
Background:
- Elevated circulating fatty acid-binding protein 4 (FABP4) is linked to obesity, insulin resistance, hypertension, and cardiovascular events.
- The impact of pharmacological agents on circulating FABP4 levels remains largely uncharacterized.
Purpose of the Study:
- To investigate the effects of angiotensin II receptor blockers (ARBs) on serum FABP4 concentrations in hypertensive patients.
- To explore the direct effects of ARBs and angiotensin II on FABP4 secretion in adipocytes.
Main Methods:
- Clinical study involving essential hypertensive patients treated with various ARBs (candesartan, olmesartan, valsartan, telmisartan).
- Measurement of serum FABP4 levels, blood pressure, adiposity, lipid profiles, and insulin sensitivity (M value via glucose clamp).
- In vitro study using 3T3-L1 adipocytes to assess FABP4 secretion under different treatments (isoproterenol, insulin, angiotensin II, ARBs).
Main Results:
- ARBs significantly decreased blood pressure and serum FABP4 concentrations (8-20%) without altering adiposity or lipid profiles.
- Candesartan treatment significantly increased insulin sensitivity (M value).
- In vitro, angiotensin II or ARBs did not affect FABP4 gene expression or secretion in adipocytes, while isoproterenol increased and insulin suppressed FABP4 secretion.
Conclusions:
- Treatment with different ARBs similarly reduces circulating FABP4 concentrations in hypertensive patients, indicating a class effect.
- This reduction in FABP4 by ARBs is not mediated by direct blockade of the angiotensin II receptor in adipocytes.
- Decreased FABP4 levels due to ARB therapy may play a role in the suppression of cardiovascular events.
Abstract:
Elevated circulating fatty acid-binding protein 4 (FABP4/A-FABP/aP2), an adipokine, is associated with obesity, insulin resistance, hypertension and cardiovascular events. However, how circulating FABP4 level is modified by pharmacological agents remains unclear. We here examined the effects of angiotensin II receptor blockers (ARBs) on serum FABP4 level. First, essential hypertensives were treated with ARBs: candesartan (8 mg day(-1); n=7) for 2 weeks, olmesartan (20 mg day(-1); n=9) for 12 weeks, and valsartan (80 mg day(-1); n=94) or telmisartan (40 mg day(-1); n=91) for 8 weeks added to amlodipine (5 mg day(-1)). Treatment with ARBs significantly decreased blood pressure and serum FABP4 concentrations by 8-20% without significant changes in adiposity or lipid variables, though the M value determined by hyperinsulinemic-euglycemic glucose clamp, a sensitive index of insulin sensitivity, was significantly increased by candesartan. Next, alterations in FABP4 secretion from 3T3-L1 adipocytes were examined under several agents. Lipolytic stimulation of the β-adrenoceptor in 3T3-L1 adipocytes by isoproterenol increased FABP4 secretion, and conversely, insulin suppressed FABP4 secretion. However, treatment of 3T3-L1 adipocytes with angiotensin II or ARBs for 2 h had no effect on gene expression or secretion of FABP4 regardless of β-adrenoceptor stimulation. In conclusion, treatment with structurally different ARBs similarly decreases circulating FABP4 concentrations in hypertensive patients as a class effect of ARBs, which is not attributable to blockade of the angiotensin II receptor in adipocytes. Reduction of FABP4 levels by ARBs might be involved in suppression of cardiovascular events.
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