PM upregulates rat mesenteric arteries 5-HT receptor via inflammatory-mediated mitogen-activated protein kinases signaling pathway.

Fine particulate matter (PM ) is an important environmental risk factor for cardiovascular diseases. However, little is known about the effects of PM on arteries. The present study investigated whether PM alters 5-hydroxytryptamine (5-HT) receptor expression and inflammatory mediators on rat mesenteric arteries, and examined the underlying mechanisms. Isolated rat mesenteric arteries segments were cultured with PM in the presence or absence of ERK1/2, JNK, and p38 pathway inhibitors. Contractile reactivity was monitored by a sensitive myograph. The expression of 5-HT receptors and inflammatory mediators were studied by a real-time polymerase chain reaction and/or by immunohistochemistry. The phosphorylation of mitogen-activated protein kinases (MAPK) pathway was detected by Western blot. Compared with the fresh or culture alone groups, 1.0 μg/mL PM cultured for 16 hours significantly enhanced contractile response induced by 5-HT and increased 5-HT receptor mRNA and protein expressions, indicating PM upregulates 5-HT receptor. SB203580 (p38 inhibitor) and U0126 (ERK1/2 inhibitor) significantly decreased PM -induced elevated contraction and mRNA and protein expression of 5-HT receptor. Cultured with PM significantly increased the mRNA expression of inflammatory mediators (NOS2, IL-1β, and TNF-α), while SB203580 decreased mRNA expression level of NOS2, IL-1β, and TNF-α. SP600125 (JNK inhibitor) decreased mRNA expression level of TNF-α and IL-1β. After PM exposure, the phosphorylation of p38 and ERK1/2 protein were increased. SB203580 and U0126 inhibited the PM caused increased phosphorylation protein of p38 and ERK1/2. In conclusion, PM induces inflammatory-mediated MAPK pathway in artery which subsequently results in enhanced vascular contraction responding to 5-HT via the upregulated 5-HT receptors.