Role of Kir2.1 in human monocyte‐derived foam cell maturation

Abstract

The role of K+ channels in macrophage immunomodulation has been well‐established. However, it remains unclear whether K+ channels are involved in the lipid uptake of macrophages. The expression and function of the inward rectifier potassium channel (Kir2.1, KCNJ2) in Human acute monocytic leukemia cell line (THP‐1) cells and human monocytes derived macrophages (HMDMs) were investigated using RT‐PCR and western blotting, and patch clamp technique. The expression of scavenger receptors in THP‐1–derived macrophages was detected using western blotting. Expressions of Kir2.1 mRNA and protein in HMDMs were significantly decreased by 60% (P < 0.05) and 90% (P < 0.001) on macrophage maturation, but overexpressed by approximately 1.3 (P > 0.05) and 3.8 times (P = 0.001) after foam cell formation respectively. Concurrently, the Kir2.1 peak current density in HMDMs, mature macrophages and foam cells, measured at −150 mV, were −22.61 ± 2.1 pA/pF, −7.88 ± 0.60 pA/pF and −13.39 ± 0.80 pA/pF respectively (P < 0.05). In association with an up‐regulation of Kir2.1 in foam cells, the SR‐A protein level was significantly increased by over 1.5 times compared with macrophages (P < 0.05). THP‐1 cells contained much less lipids upon Kir2.1 knockdown and cholesterol ester/total cholesterol ratio was 29.46 ± 2.01% (P < 0.05), and the SR‐BI protein level was increased by over 6.2 times, compared to that of macrophages (P < 0.001). Kir2.1 may participate in macrophage maturation and differentiation, and play a key role in lipid uptake and foam cell formation through modulating the expression of scavenger receptors.

miR‐497 accelerates oxidized low‐density lipoprotein‐induced lipid accumulation in macrophages by repressing the expression of apelin

“…THP‐1 monocytes were stimulated to differentiate into macrophages by incubation for 72 h with 100 nM phorbol 12‐myristate 13‐acetate (PMA; Sigma–Aldrich). To induce the formation of foam cells, PMA‐differentiated THP‐1 macrophages were incubated with 50 μg/mL oxLDL (Biosynthesis Biotechnology Company, Beijing, China) for 48 h, as described previously (Zhang et al, ).…”

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

“…The Kir2.1 channel is expressed by macrophages and, by hyperpolarizing the membrane potential, it determines the increase of intracellular calcium levels through the activation of the alfa 1H T-type calcium channel [ 119 , 120 ]. The inward calcium current may stimulate the expression of several proteins, among which the scavenger receptor [ 120 ]. Therefore, the Kir2.1 channel may promote ox-LDL intake by macrophages and foam cell formation, regulating scavenger receptor expression [ 120 ].…”

“…The inward calcium current may stimulate the expression of several proteins, among which the scavenger receptor [ 120 ]. Therefore, the Kir2.1 channel may promote ox-LDL intake by macrophages and foam cell formation, regulating scavenger receptor expression [ 120 ].…”

4β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters

“…It can be hypothesized that OAZ2 suppression leads to an increase in intracellular polyamine levels which enhance the KCNJ2mediated uptake of potassium ions, and perhaps KCNJ2 expression is then suppressed in a counter-regulatory loop. In macrophages, KCNJ2 is known to have a role in lipid uptake and foam cell formation by modulating the expression of SR-A, SR-B1, and CD36 (Zhang et al, 2016). It is not known if LXR is involved in the regulation of OAZ2 or KCNJ2.…”