Expression of α7 Nicotinic ACh Receptors in Blood Mononuclear Cells: Correlation with Impaired Baroreflex Sensitivity in Patients with Heart Failure

Autonomic imbalance, including depleted parasympathetic drive, is a fundamental pathophysiological feature of heart failure (HF). In clinical studies, parasympathetic withdrawal is assessed using arterial baroreflex sensitivity (BRS). Parasympathetic activity can also be tracked based on the assessment of molecular elements of cholinergic signaling in target cells. Hence, we investigated whether BRS is associated with the mRNA expression of nicotinic cholinergic receptors (α7nAChR) in peripheral blood mononuclear cells (PBMCs) in subjects with and without HF. We examined 39 patients with stable systolic HF (35 men, 4 women, age 56 ± 13 years, left ventricular ejection fraction, LVEF, 30 ± 9%) and 17 healthy subjects (6 men, 11 women, age 60 ± 11 years, LVEF 64 ± 9%). BRS was assessed using a phenylephrine test. Relative transcript levels of α7nAChRs in PBMCs were analyzed using a real-time PCR. Patients with HF, as compared to healthy subjects, demonstrated much higher expression of α7nAChR mRNA in PBMCs (4.4 ± 2.2 vs. 1.4 ± 2.2 AU; P < 0.01) without a difference in BRS (P > 0.2). In a combined sampling including subjects with and without HF, BRS negatively correlated with the content of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = –0.43, P < 0.05). In such sampling, α7nAChR expression in PBMCs also negatively correlated with LVEF (r = –0.39, P < 0.05) and was positively associated with plasma NT-proBNP (r = 0.38, P < 0.01), but without associations with other clinical and laboratory measures. Expression of α7nAChRs in PMBCs is inversely correlated with BRS (r = –0.50, P < 0.01). Thus, autonomic imbalance confirmed by physiological tests is accompanied by increased expression of α7 nicotinic receptors on circulating immune cells.

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