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High and low hematocrit (Hct) and hemoglobin (Hb) levels are associated with the risk of cardiovascular disease. The purpose of this study was to determine the relationships of Hct, Hb and red blood cells (RBCs) with vascular function and structure. We measured flow-mediated vasodilation (FMD), nitroglycerin-induced vasodilation (NID), brachial intima media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in 807 men. The subjects were divided into six groups according to the levels of Hct, Hb and RBCs. NID was highest in the 46.0–48.9% Hct group among the six groups according to Hct levels. Brachial IMT was lowest in the 46.0–48.9% Hct group among the six groups. There were no significant differences in FMD and baPWV among the six groups. We used 46.0–48.9% Hct as a reference to define the lower tertile. The adjusted odds ratio of being in the low tertile of NID was significantly higher in the < 42.9% and ≥ 49.0% Hct groups. Adjusted odds ratio of being in the low tertile of brachial IMT was significantly lower in the < 39.9% Hct groups. Similar results were obtained for Hb and RBCs. Low and high levels of Hct, Hb and RBCs were associated with vascular smooth muscle dysfunction, and low Hct levels were associated with abnormal vascular structure. Increases in the levels of Hct, Hb and RBCs within normal ranges may have beneficial effects on the vasculature.

The percentage of people aged 80 years or older in Japan has been increasing. The purpose of this study was to investigate the association between vascular functions and aging in the elderly population and to clarify the characteristics of vascular functions in subjects aged 80 years or older. We measured flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), and brachial-ankle pulse wave velocity (baPWV) in 737 subjects aged 60 years or older who visited the outpatient clinic at Hiroshima University Hospital. FMD and NID were significantly lower in subjects aged 80 years or older than in subjects aged 60–69 years or in subjects aged 70–79 years (1.9 ± 2.0% vs. 2.9 ± 2.6% and 2.7 ± 2.6%, P = 0.008 and P = 0.03, respectively and 8.6 ± 5.1% vs. 12.1 ± 5.6% and 11.2 ± 5.5%, P < 0.001 and P < 0.001, respectively). baPWV was significantly higher in subjects aged 80 years or older than in subjects aged 60–69 years or in subjects aged 70–79 years (1978 ± 452 cm/s vs. 1724 ± 319 cm/s and 1811 ± 318 cm/s, P < 0.001 and P < 0.001, respectively). Age over 80 years was significantly associated with lower FMD (OR, 2.02; 95% CI, 1.19–3.42; P = 0.01), lower NID (OR, 3.62; 95% CI, 2.13–6.17; P < 0.001), and higher baPWV (OR, 3.48; 95% CI, 1.99–6.08; P < 0.001) after adjustment for other cardiovascular risk factors. Vascular functions, including endothelial function, vascular smooth muscle function, and arterial stiffness, were shown to be further impaired in subjects aged 80 years or older, suggesting that vascular functions continue to be impaired throughout life with aging.

It is established that smoking is a major risk factor of atherosclerosis. Endothelial dysfunction occurs in the initial step in the pathogenesis of atherosclerosis and plays a critical role in the development of atherosclerosis. The purpose of this study was to evaluate the association between smoking status and endothelial function in detail in men. We measured flow-mediated vasodilation (FMD) in 2209 Japanese men including 1181 men who had never smoked and 1028 current smokers. All of the participants were divided into five groups by smoking pack-years: never smoker group (= 0), light smoker group (> 0 to 10), moderate smoker group (> 10 to 20), heavy smoker group (> 20 to 30) and excessive smoker group (> 30). FMD significantly decreased in relation to pack-years (6.6 ± 3.4% in the never smoker group, 6.8 ± 3.0% in the light smoker group, 6.5 ± 2.9% in the moderate smoker group, 5.9 ± 2.9% in the heavy smoker group, and 4.9 ± 2.7% in the excessive smoker group; P  < 0.001). After adjustment for age (≥ 65 years), body mass index, systolic blood pressure, low-density lipoprotein cholesterol, glucose, and year of recruitment, FMD was significantly smaller in the excessive smoker group than in the never smoker group as a reference group (OR 1.95, 95% CI 1.42 to 2.67; P  < 0.001). These findings suggest that FMD decreases with an increase in the number of cigarettes smoked and that excessive smoking is associated with endothelial dysfunction. Cigarette smoking is harmful to vascular function in men who are heavy smokers.

Cell therapy using intramuscular injections of autologous bone-marrow mononuclear cells (BM-MNCs) improves clinical symptoms and can prevent limb amputation in atherosclerotic peripheral arterial disease (PAD) patients with critical limb ischemia (CLI). The purpose of this study was to evaluate the effects of the number of implanted BM-MNCs on clinical outcomes in atherosclerotic PAD patients with CLI who underwent cell therapy. This study was a retrospective observational study with median follow-up period of 13.5 years (range, 6.8–15.5 years) from BM-MNC implantation procedure. The mean number of implanted cells was 1.2 ± 0.7 × 10 9 per limb. There was no significant difference in number of BM-MNCs implanted between the no major amputation group and major amputation group (1.1 ± 0.7 × 10 9 vs. 1.5 ± 0.8 × 10 9 per limb, P = 0.138). There was also no significant difference in number of BM-MNCs implanted between the no death group and death group (1.5 ± 0.9 × 10 9 vs. 1.8 ± 0.8 × 10 9 per patient, P = 0.404). Differences in the number of BM-MNCs (mean number, 1.2 ± 0.7 × 10 9 per limb) for cell therapy did not alter the major amputation-free survival rate or mortality rate in atherosclerotic PAD patients with CLI. A large number of BM-MNCs will not improve limb salvage outcome or mortality.

Hypertension is associated with vascular failure, such as increased arterial stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. The purpose of this study was to investigate the relationship between out-of-office blood pressure and vascular function in patients receiving antihypertensive drugs. We assessed out-of-office blood pressure, including daytime and night-time blood pressure, by home blood pressure monitoring and performed vascular function tests, including brachial-ankle pulse wave velocity (baPWV), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID), in 169 patients receiving antihypertensive drugs, of whom 86 (50.9%) had normotension, 23 (13.6%) had isolated nocturnal hypertension (night-time systolic blood pressure ≥120 mm Hg), 26 (15.4%) had isolated daytime hypertension (daytime systolic blood pressure ≥135 mm Hg), and 34 (20.1%) had sustained hypertension (daytime and nocturnal hypertension). baPWV was significantly higher in patients with sustained hypertension than in those without sustained hypertension (1585 ± 257 cm/s in normotension; 1687 ± 267 cm/s in isolated nocturnal hypertension; 1688 ± 313 cm/s in isolated daytime hypertension; and 1923 ± 399 cm/s in sustained hypertension; P < 0.001). baPWV above the cutoff value of 1858 cm/s, derived from receiver operating characteristic curve analysis to diagnose patients with sustained hypertension, was significantly associated with sustained hypertension after adjustment of other confounding factors (odds ratio, 5.01; 95% confidence interval, 1.94-13.41; P < 0.001). In contrast, there was no significant association of home blood pressure status with FMD or NID in these patients. In patients receiving antihypertensive drugs, baPWV was significantly associated with sustained hypertension, whereas FMD and NID were impaired regardless of the home blood pressure status.

Critical limb ischemia (CLI) is associated with a high risk of limb amputation. It has been shown that cell therapy is safe and has beneficial effects on ischemic clinical symptoms in patients with CLI. The aim of this study was to further investigate the outcomes of intramuscular injection of autologous bone-marrow mononuclear cells (BM-MNCs) in a long-term follow-up period in atherosclerotic peripheral arterial disease (PAD) patients who have no optional therapy. This study was a retrospective and observational study that was carried out to evaluate long-term clinical outcomes in 42 lower limbs of 30 patients with atherosclerotic PAD who underwent BM-MNC implantation. The median follow-up period was 9.25 (range, 6–16) years. The overall amputation-free rates were 73.0% at 5 years after BM-MNC implantation and 70.4% at 10 years in patients with atherosclerotic PAD. The overall amputation-free rates at 5 years and at 10 years after implantation of BM-MNCs were significantly higher in atherosclerotic PAD patients than in internal controls and historical controls. There were no significant differences in amputation rates between the internal control group and historical control group. The rate of overall survival was not significantly different between the BM-MNC implantation group and the historical control group. Implantation of autologous BM-MNCs is feasible for a long-term follow-up period in patients with CLI who have no optional therapy.

ObjectiveThe aim of this study was to determine the relationship of haemoglobin A1c (HbA1c) level with flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) in patients with type 2 diabetes.DesignCross-sectional study.Setting22 university hospitals and affiliated clinics in Japan.Participants1215 patients with type 2 diabetes including 349 patients not taking antidiabetic drugs.MeasuresWe evaluated FMD and HbA1c level. All patients were divided into four groups based on HbA1c level: <6.5%, 6.5%–6.9%, 7.0%–7.9% and ≥8.0%.ResultsAn inverted U-shaped pattern of association between HbA1c level and FMD was observed at the peak of HbA1c of about 7%. FMD was significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5%–6.9% group and HbA1c 7.0%–7.9% group (p<0.001 and p<0.001), and FMD values were similar in the HbA1c <6.5% group and HbA1c ≥8.0% group. There were no significant differences in NID values among the four groups. After adjustments for confounding factors, FMD was significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5%–6.9% and HbA1c 7.0%–7.9% group (p=0.002 and p=0.04). In patients not taking antidiabetic drugs, FMD was also significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5%–6.9% group and HbA1c 7.0%–7.9% group (p<0.001 and p=0.02), and there were no significant differences in NID values among the four groups.ConclusionsThese findings suggest that there is an inverted U-shaped pattern of association between FMD and HbA1c and that a low HbA1c level of <6.5% is associated with endothelial dysfunction.Trial registration numberUMIN000012950, UMIN000012951, UMIN000012952 and UMIN000003409.

The aims were to evaluate the relationship between idiopathic hyperaldosteronism (IHA) and grade of vascular function in the macrovasculature and microvasculature. Vascular function, including reactive hyperemia index (RIH), flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID) were evaluated in 52 patients with IHA, 53 patients with aldosterone-producing adenoma (APA), and 52 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). Log RHI was lower in the IHA and APA groups than in the EHT group (0.54 ± 0.25 and 0.55 ± 0.23 versus 0.79 ± 0.28; P < 0.01, respectively). FMD was lower in the APA group than in the EHT group (3.4 ± 2.1% versus 4.8 ± 2.8%; P = 0.02), whereas there was no significant difference in FMD between the IHA and the APA and EHT groups. NID was lower in the APA group than in the EHT group (10.0 ± 4.5% versus 12.5 ± 5.7%; P = 0.03), whereas there was no significant difference in NID between the IHA, APA, and EHT groups. Multiple regression analysis revealed an association of log RHI with plasma aldosterone concentration (t = -2.24; P = 0.03) and an association of FMD with plasma aldosterone concentration (t = -3.07; P < 0.01). Microvascular endothelial function was impaired in patients with IHA compared with that in patients with EHT.

ObjectivesThe purpose of this study was to evaluate the relationship between high-density lipoprotein cholesterol (HDL-C) levels and endothelial function in women.DesignCross-sectional study.Setting22 university hospitals and affiliated clinics in Japan.Participants1719 Japanese women aged 17–90 years who were not receiving lipid-lowering therapy.MeasuresWe evaluated flow-mediated vasodilation (FMD) and serum levels of HDL-C. All participants were divided into four groups by HDL-C level: low HDL-C (<40 mg/dL), moderate HDL-C (40–59 mg/dL), high HDL-C (60–79 md/dL) and extremely high HDL-C (≥80 mg/dL).ResultsUnivariate regression analysis revealed a significant relationship between FMD and HDL-C (r=0.12, p<0.001). FMD values were significantly smaller in the low HDL-C group (5.2%±3.8%) and moderate HDL-C group (5.2%±3.8%) than in the extremely high HDL-C group (6.7%±3.4%) (p=0.024 and p=0.003, respectively), while there was no significant difference in FMD between the high HDL-C group and the extremely high HDL-C group. Multiple logistic regression analysis did not show a significant association between HDL-C levels and FMD.ConclusionsEndothelial function increased in relation to HDL-C levels. However, there was no association of HDL-C levels with endothelial function after adjustment of traditional cardiovascular risk factors in women.Trial registration numberUMIN000012950; Results.

Division and partitioning of microbodies (peroxisomes) of the green alga Klebsormidium flaccidum, whose cells contain a single microbody, were investigated by electron microscopy. In interphase, the rod-shaped microbody is present between the nucleus and the single chloroplast, oriented perpendicular to the pole-to-pole direction of the future spindle. A centriole pair associates with one distal end of the microbody. In prophase, the microbody changes not only in shape, from a rodlike to a branched form, but also in orientation, from perpendicular to parallel to the future pole-to-pole direction. Duplicated centriole pairs are localized in close proximity to both distal ends of the microbody. In metaphase, the elongated microbody flanks the open spindle, with both distal ends close to the centriole pair at either spindle pole. The microbody further elongates in telophase and divides after septum formation (cytokinesis) has started. The association between the centrioles and both distal ends of the microbody is maintained throughout mitosis, resulting in the distal ends of the elongated microbody being fixed at the cellular poles. This configuration of the microbody may be favorable for faithful transmission of the organelle during cell division. After cytokinesis is completed, the microbody reverts to the perpendicular orientation by changing its shape. Microtubules radiating from the centrosomes flank the side of the microbody throughout mitosis. The close association of centrosomes and microtubules with the microbody is discussed in respect to the partitioning of the microbody in this alga.