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Recent studies have indicated that protease-activated receptor-1 (PAR-1) is involved in cytoprotective and anti-inflammatory responses in endothelial cells (ECs). However, the role of PAR-1 in laminar flow-mediated atheroprotective responses remains unknown. Herein, we investigated whether PAR-1 regulates laminar flow-mediated mechanotransduction in ECs. Confocal analysis showed that PAR-1 was internalized into early endosomes in response to laminar flow. In addition, flow cytometry analysis showed that cell surface expression of PAR-1 was reduced by laminar flow, suggesting that PAR-1 was activated in response to laminar flow. Depletion of PAR-1 using human PAR-1 siRNA inhibited unidirectional laminar flow-mediated actin stress fiber formation and cellular alignment as well as atheroprotective gene expressions in HUVECs. Moreover, PAR-1 knockdown inhibited laminar flow-stimulated eNOS phosphorylation, and inhibited the phosphorylations of Src, AMPK, ERK5 and HDAC5. Furthermore, PAR-1 depletion inhibited laminar flow-mediated anti-inflammatory responses as demonstrated by reduced TNFα-induced VCAM-1 expression and by monocyte adhesion to HUVECs, and prevented laminar flow-mediated anti-apoptotic response. An investigation of the role of PAR-1 in vasomotor modulation using mouse aortic rings revealed that acetylcholine-induced vasorelaxation was diminished in PAR-1 deficient mice compared to littermate controls. Taken together, these findings suggest that PAR-1 be viewed as a novel pharmacologic target for the treatment of vascular diseases, including atherosclerosis.

In order to determine the fungal strain and fermentation period which produce the highest antioxidant activity of fermented soy product, soybean was fermented with Aspergillus oryzae NL 5 isolated from Korean traditional meju produced in Sunchang Yeastopia Land in Korea, and was subjected to analyzing isoflavone profiles and assaying antioxidant activity. Antioxidant potential of the samples was evaluated by ferric reducing antioxidant power assay, 2,2'-azinobis (2-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity and total phenolic contents. In addition, antioxidant assay using fluorescent probes, 2',7'-dichlorofluorescin diacetate and dihydroethidium, in HepG2 cells was conducted for the samples. The results showed that both high isoflavone variety Aga 3 and medium isoflavone variety Daewon of soybean fermented with Asp oryzae NL5 for 4 to 5 d showed the highest increase in free isoflavone contents, together with the highest antioxidant activity. In conclusion, the antioxidant activity of fermented soy was proportional to the concentration of free isoflavones, and was significantly influenced by total isoflavone content of soybean variety and fermentation period. Practical Application:  Isoflavone profile and antioxidant capacity of soybean were widely variable during fermentation with Asp oryzae, and thereby it is recommended that meju (or koji) preparation condition, in particular, fermentation time is carefully optimized to maximize the antioxidant capacity of soy products fermented by Asp oryzae.