Rutaecarpine Reverses the Altered Connexin Expression Pattern Induced by Oxidized Low-density Lipoprotein in Monocytes.

Adhesion of monocytes to the vascular endothelium is crucial in atherosclerosis development. Connexins (Cxs) which form hemichannels or gap junctions, modulate monocyte-endothelium interaction. We previously found that rutaecarpine, an active ingredient of the Chinese herbal medicine Evodia, reversed the altered Cx expression induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells, and consequently decreases the adhesive properties of endothelial cells to monocytes. This study further investigated the effect of rutaecarpine on Cx expression in monocytes exposed to ox-LDL. In cultured human monocytic cell line THP-1, ox-LDL rapidly reduced the level of atheroprotective Cx37 but enhanced that of atherogenic Cx43, thereby inhibiting adenosine triphosphate release through hemichannels. Pretreatment with rutaecarpine recovered the expression of Cx37 but inhibited the upregulation of Cx43 induced by ox-LDL, thereby improving adenosine triphosphate-dependent hemichannel activity and preventing monocyte adhesion. These effects of rutaecarpine were attenuated by capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. The antiadhesive effects of rutaecarpine were also attenuated by hemichannel blocker 18α-GA. This study provides additional evidence that rutaecarpine can modulate Cx expression through transient receptor potential vanilloid subtype 1 activation in monocytes, which contributes to the antiadhesive properties of rutaecarpine.

Source regional contributions to PM2.5 in a megacity in China using an advanced source regional apportionment method.

To quantify contributions of individual source categories from diverse regions to PM2.5, PM2.5 samples were collected in a megacity in China and analyzed through a newly developed source regional apportionment (SRA) method. Levels, compositions and seasonal variations of speciated PM2.5 dataset were investigated. Sources were determined by Multilinear Engine 2 (ME2) model, and results showed that the PM2.5 in Tianjin was mainly influenced by secondary sulphate & secondary organic carbon SOC (percent contribution of 26.2%), coal combustion (24.6%), crustal dust & cement dust (20.3%), secondary nitrate (14.9%) and traffic emissions (14.0%). The SRA method showed that northwest region R2 was the highest regional contributor to secondary sources, with percent contributions to PM2.5 being 9.7% for secondary sulphate & SOC and 6.0% for secondary nitrates; the highest coal combustion was from local region R1 (6.2%) and northwest R2 (8.0%); the maximum contributing region to crustal & cement dust was southeast region R4 (5.0%); and contributions of traffic emissions were relatively spatial homogeneous. The seasonal variation of regional source contributions was observed: in spring, the crustal and cement dust contributed a higher percentage and the R4 was an important contributor; the secondary process attributed an increase fraction in summer; the mixed coal combustion from southwest R5 enhanced in autumn.

Seasonal and regional variations of source contributions for PM10 and PM2.5 in urban environment.

To characterize the sources of to PM10 and PM2.5, a long-term, speciate and simultaneous dataset was sampled in a megacity in China during the period of 2006-2014. The PM concentrations and PM2.5/PM10 were higher in the winter. Higher percentages of Al, Si, Ca and Fe were observed in the summer, and higher concentrations of OC, NO3(-) and SO4(2-) occurred in the winter. Then, the sources were quantified by an advanced three-way model (defined as an ABB three-way model), which estimates different profiles for different sizes. A higher percentage of cement and crustal dust was present in the summer; higher fractions of coal combustion and nitrate+SOC were observed in the winter. Crustal and cement contributed larger portion to coarse part of PM10, whereas vehicular and secondary source categories were enriched in PM2.5. Finally, potential source contribution function (PSCF) and source regional apportionment (SRA) methods were combined with the three-way model to estimate geographical origins. During the sampling period, the southeast region (R4) was an important region for most source categories (0.6%-11.5%); the R1 (centre region) also played a vital role (0.3-6.9%).

Rutaecarpine prevented dysfunction of endothelial gap junction induced by Ox-LDL via activation of TRPV1.

Gap junctions, which is formed by connexins, has been proved to play an important role in the atherogenesis development. Rutaecarpine was reported to inhibited monocyte migration, which indicates its potential for anti-atherosclerosis activity. This study evaluated the effect of rutaecarpine on endothelial dysfunction, and focused on the regulation of connexin expression in endothelial cells by rutaecarpine. Endothelia damage was induced by exposing HUVEC-12 to Ox-LDL (100mg/l) for 24h, which decreased the expression of protective proteins Cx37 and Cx40, but induced atherogenic Cx43 expression, in both mRNA and protein levels, concomitant with the impaired propidium iodide diffusion through the gap junctions. Pretreatment with rutaecarpine effectively recovered the expression of Cx37 and Cx40, but inhibited Cx43 expression, thereby improving gap junction communication and significantly prevented the endothelial dysfunction. Consequently, the cell viability and nitric oxide production were increased, lactate dehydrogenase production was decreased and monocyte adhesion was inhibited. These protective effects of rutaecarpine were remarkably attenuated by pretreatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid subtype 1 (TRPV1). In summary, this study is the first to report that rutaecarpine prevents endothelial injury and gap junction dysfunction induced by Ox-LDL in vitro, which is related to regulation of connexin expression patterns via TRPV1 activation. These results suggest that rutaecarpine has the potential for use as an anti-atherosclerosis agent with a novel mechanism.