Abstract:
Objective To investigate the mechanism of the gap junction protein connexin 43 (Cx43) mediating the inflammatory response of pulmonary artery smooth muscle cells (PASMCs) in nicotine-induced pulmonary artery remodeling in mice.
Methods Thirty-two 5-week-old male C57BL/6J mice and Tagln-Cre(+); Cx43flox/WT mice each were randomly divided into control group (sterile water for injection), 0.02 mg/(kg·d) nicotine group, 0.2 mg/(kg·d) nicotine, and 2.0 mg/(kg·d) nicotine group, with 8 mice in each group. The mice were treated through nasal drip according to body weight, once a day at a fixed time for continuous 8 weeks. After exposure, the mice were examined for pulmonary arterial remodeling with hematoxylin-eosin (HE) staining. The primary distal PASMCs of C57BL/6J mice and Tagln-Cre(+); Cx43flox/WT mice were cultured by magnetic separation. The protein expression levels of Cx43, tumor necrosis factor-alpha, interleukin-1β, and interleukin-6 in mouse PASMCs were measured by Western blot.
Results Compared with C57BL/6J mice in the control group, C57BL/6J mice in the nicotine groups showed a generally increasing trend in body weight, and the body weight growth slowed down with the increase in nicotine concentrations; the distal pulmonary arteries showed typical pathological features of arterial remodeling including wall thickening and lumen narrowing; and the expression of Cx43 was up-regulated in a dose-dependent manner. Tagln-Cre(+); HE staining results of Cx43flox/WT mice showed milder wall thickening and lumen narrowing of pulmonary arteries and lower expression levels of the inflammatory factors in PASMCs.
Conclusion Downregulating Cx43 can alleviate nicotine-induced inflammatory responses in distal PASMCs, thereby improving pulmonary arterial remodeling in mice.
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