Cytochrome P450 4F2 (CYP4F2) activity is thought to be a factor in the pathogenesis of hypertension through its bioactive metabolite 20-hydroxyeicosatetraenoic acid (20-HETE). We previously found that a gain-in-function CYP4F2 variant in a Chinese cohort was associated with elevated urinary 20-HETE and hypertension. To further explore this association we generated a transgenic mouse model expressing CYP4F2 driven by a modified mouse kidney androgen-regulated protein promoter. This heterologous promoter regulated the expression of luciferase and his-tagged CYP4F2 in transfected HEK 293 cells. In the kidney of transgenic mice, CYP4F2 was localized to renal proximal tubule epithelia and was expressed at a higher level than in control mice, leading to increased urinary 20-HETE excretion. Assessment of CYP4F2 activity by an arachidonic acid hydroxylation assay showed that 20-HETE production was significantly higher in kidney microsomes of transgenic mice compared to control mice, as was their systolic blood pressure. There was a positive correlation of blood pressure with urinary 20-HETE levels. Our results show that increased expression of CYP4F2 in mice enhanced 20-HETE production and elevated blood pressure.
These findings demonstrated a new mechanism by which the alcohol repressed the GSR and POR expression via up-regulation of miR-214 and in turn induced oxidative stress in liver cells.
The effects of nano-TiO2(NT) on microstructures and mechanical properties of cement mortars were studied by scanning electron microscopy (SEM), X-ray diffraction (XRD), and mercury intrusion porosimetry (MIP). Results show that 3% NT can remarkably increase the tensile/flexural strengths (i.e., the toughness is improved) and promote the precipitation of AFt crystal. The flexural and tensile strengths have significant positive correlation to the formation amount of AFt. The pores of mortars can be significantly refined and shift to harmless pores by controlling the growth of CH crystal and increasing the hydration reaction rate. The durability of cement-based materials is discussed by testing their water absorption and water-vapour permeability. Results show that the addition of 3% NT can decrease the water absorption ratio by 40–65%, water absorption coefficients by more than 40%, and water-vapour permeability coefficients by 43.9%, indicating that 3% NT can effectively improve the compactness and durability of cement-based materials.
We conclude that reproducible MCA infarcts can be produced in aged rats by craniotomy and that these lesions may be compatible with long-term survival. This should be a useful technique for studying therapeutic interventions and rehabilitation strategies in an animal model that immunologically and neurochemically more closely resembles humans at risk for stroke.
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