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The process of vascular remodeling is associated with increased hypoxia. However, the contribution of hypoxia-inducible factor 1α (HIF1α), the key transcription factor mediating cellular hypoxic responses, to vascular remodeling is established, but not completely understood. In the angiotensin II (Ang II)-induced vascular remodeling model, HIF1α was increased and activated in vascular smooth muscle cells (VSMCs). Selective genetic disruption of Hif1a in VSMCs markedly ameliorated Ang II-induced vascular remodeling, as revealed by decreased blood pressure, aortic thickness, collagen deposition, inflammation, and aortic stiffness. VSMC Hif1a deficiency also specifically suppressed Ang II-induced infiltration of CD45 + CD11b + F4/80 + CD206 − M1 macrophages into the vessel. Mechanistically, HIF1α deficiency in VSMCs dramatically suppressed the expression of CCL7, a chemokine critical for macrophage recruitment. Bioinformatic analysis and chromatin immunoprecipitation assays revealed three functional hypoxia-response elements in the Ccl7 promoter, indicating that Ccl7 is a direct HIF1α target gene. Blocking CCL7 with antibody in vivo alleviated Ang II-induced hypertension and vascular remodeling, coincident with decreased macrophage infiltration. This study provides direct evidence that HIF1α activation in VSMCs exacerbates Ang II-induced macrophage infiltration and resultant vascular remodeling via its target gene Ccl7 , and thus may serve as a potential therapeutic target for remodeling-related vascular disease.

A gradient elution system for pressure-driven liquid chromatography (LC) on a chip was developed for carrying out faster and more efficient chemical analyses. Through computational fluid dynamics simulations and an experimental study, we found that the use of a cross-Tesla structure with a 3 mm mixing length was effective for mixing two liquids. A gradient elution system using a cross-Tesla mixer was fabricated on a 20 mm × 20 mm silicon chip with a separation channel of pillar array columns and a sample injection channel. A mixed solution of water and fluorescein in methanol was delivered to the separation channel 7 s after the gradient program had been started. Then, the fluorescence intensity increased gradually with the increasing ratio of fluorescein, which showed that the gradient elution worked well. Under the gradient elution condition, the retention times of two coumarin dyes decreased with the gradient time. When the gradient time was 30 s, the analysis could be completed in 30 s, which was only half the time required compared to that required for an isocratic elution. Fluorescent derivatives of aliphatic amines were successfully separated within 110 s. The results show that the proposed system is promising for the analyses of complex biological samples.