Biomedical subjects
Yoshio Fujioka
Publications and source records attributed to Yoshio Fujioka.
Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability.
BACKGROUND: Epidemiologic investigations suggest that fish oil, which contains eicosapentaenoic acid (EPA), has favorable cardiovascular effects. Fish oil improves endothelial function in subjects with hypercholesterolemia or diabetes. However, controversy persists regarding relationships between primary hypertriglyceridemia and endothelial dysfunction. Moreover, lipoproteins are more susceptible to oxidation in vitro after incorporation of fish oil. METHODS: We determined the effects of EPA on serum lipids, susceptibility of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) to oxidation, and endothelial function in hypertriglyceridemic (HTG) subjects. In 8 men with untreated primary hypertriglyceridemia (plasma triglyceride between 150 and 500 mg/dL) and 7 control subjects (triglyceride below 150 mg/dL), forearm blood flow (FBF) responses were tested. In HTG subjects, this was repeated 3 months after initiation of EPA (1800 mg/day). Cu2+-induced oxidation of VLDL and LDL was determined by serial measurement of conjugated dienes. We used lag time, which corresponded to the period when the lipoproteins were resistant to oxidation, as a parameter of oxidizability. FBF responses to acetylcholine and sodium nitroprusside were determined by strain-gauge plethysmography. RESULTS: Plasma triglyceride in HTG subjects fell 31% with EPA supplementation. Before EPA, VLDL and LDL lag times in HTG subjects were shorter than in control subjects. EPA further reduced lag time for VLDL but not LDL. The FBF response to acetylcholine (but not to nitroprusside) was significantly less in HTG subjects before EPA than in control subjects. EPA normalized the FBF response to acetylcholine. CONCLUSIONS: EPA improves endothelial function in HTG subjects despite increasing in VLDL oxidizability.
Augmented diurnal variations of the cardiac renin-angiotensin system in hypertensive rats.
There are several controversies concerning the enhanced gene expression of cardiac renin-angiotensin system components in spontaneously hypertensive rats (SHR) compared with their normotensive control Wistar-Kyoto (WKY) rats. We hypothesized that these discrepancies arise from circadian fluctuations in gene expression. We examined the circadian mRNA expression of renin, angiotensinogen, ACE, and angiotensin type 1a (AT1a) and type 2 (AT2) receptors in the hearts of SHR and WKY rats by real-time quantitative reverse transcription-polymerase chain reaction. The cardiac mRNA expression of the renin-angiotensin system components showed circadian oscillations in both SHR and WKY rats. The amplitudes of these circadian fluctuations were greater in the SHR than in the WKY rats. The mRNA levels of the renin-angiotensin system components were also increased in the SHR compared with the WKY rats at many time points (especially during the dark phase). However, the levels of ACE, AT1a receptor, and AT2 receptor mRNA in the SHR and WKY rats were almost the same during the late light phase. In contrast to mRNA expression, ACE activity was similar both at the time of maximum and minimum mRNA expression. The AT1 receptor antagonist candesartan upregulated AT1a receptor mRNA and downregulated ACE mRNA at specific time points only in the SHR group. Our findings of differential diurnal expression of cardiac renin-angiotensin system genes in SHR and WKY rats appear to explain the discrepancies between prior studies. However, the physiological relevance of the differential circadian mRNA expression of the renin-angiotensin system components remains to be elucidated.
Circadian expression of plasminogen activator inhibitor-1 in angiotensin II type 1a receptor knockout mice.
Both the peripheral biological clock and the renin-angiotensin system regulate mRNA expression of plasminogen activator inhibitor-1 (PAI-1). Our objective was to determine whether angiotensin II (Ang II) type 1 (AT1) receptor-mediated signaling contributes to the development of circadian expression of PAI-1 and clock genes in the heart, aorta, liver, and kidney. We sacrificed AT1a receptor knockout (AT1a-KO) and wild-type (WT) 12 week-old mice every 4 hr. We examined mRNA expression for PAI-1 and clock genes (Per2, Bmal1, and Clock) in heart, aorta, liver, and kidney by using the quantitative reverse transcription-polymerase chain reaction. PAI-1 mRNA showed circadian oscillation with a peak occurring during the light phase in the heart, liver, aorta, and kidney of WT mice. Peak expression of PAI-1 in the liver and aorta was decreased in AT1a-KO mice. On the other hand, cardiac PAI-1 expression in AT1a-KO mice was reduced in the dark phase, during which time its expression level was low. There were no significant differences between WT and AT1a-KO mice in renal PAI-1 expression. Clock genes oscillated synchronously in WT and AT1a-KO mice, and there were no significant differences between the WT and the AT1a-KO mice in their expression. Plasma angiotensin II showed little oscillation in the WT mice. We conclude that AT1a receptor-mediated Ang II signaling modulates the circadian expression of PAI-1 in an organ-specific manner. The effect of the renin-angiotensin system on PAI-1 expression appears to be independent of peripheral clock gene expression.