Background-Although lipoprotein(a) (Lp[a]) is a risk factor for atherosclerosis, no study has documented the effects of Lp(a) on angiogenesis. In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. In addition, we examined the feasibility of gene therapy by using an angiogenic growth factor, hepatocyte growth factor (HGF), to treat PAD in the presence of high Lp(a). Methods and Results-In Lp(a) transgenic mice, the degree of natural recovery of blood flow after operation was significantly lower than that in nontransgenic mice. Of importance, there was a significant negative correlation between serum Lp(a) concentration and the degree of natural recovery of blood flow (PϽ0.05). In addition, Lp(a) significantly stimulated the growth of vascular smooth muscle, accompanied by the phosphorylation of ERK. These data demonstrated the association of impairment of collateral formation with serum Lp(a) concentration. Thus, we examined the feasibility of therapeutic angiogenesis by using HGF, with the goal of progression to human gene therapy. In a large proportion of these patients, the anatomic extent and the distribution of arterial occlusive disease make the patients unsuitable for operative or percutaneous revascularization. Thus, the disease frequently follows an inexorable downhill course. 2,3 One of the risk factors related to peripheral arterial disease is a high concentration of serum lipoprotein(a) (Lp[a]) because Lp(a) is also a risk factor for atherosclerosis, restenosis after angioplasty, ischemic heart disease, and cerebral stroke. 4 -9 Lp(a) consists of LDL with an additional protein component, apolipoprotein (a) (apo [a]), a homologue of plasminogen. 10 Lp(a) and apo(a) have been thought to enhance proliferation of human vascular smooth muscle cells (VSMCs). [11][12][13][14] On the other hand, Lp(a) has been postulated to bind to endothelial cells and macrophages and to extracellular components such as fibrin and inhibit cell-associated plasminogen activation. 15,16 Moreover, the inhibition of activation of transforming growth factor (TGF)-␤ by Lp(a) because of its strong homology to plasminogen has been reported. 11 Because TGF-␤ is also known to have proangiogenic properties, Lp(a) might inhibit angiogenesis from this aspect. In contrast, there is less evidence for the stimulation of Lp(a) on angiogenesis, although the proliferation of VSMCs might promote collateral formation in the case that endothelial cells would be stimulated by Lp(a). Nevertheless, no [17][18][19][20] Thus, a strategy for therapeutic angiogenesis with the use of angiogenic growth factors should be considered for the treatment of patients with critical limb ischemia or myocardial infarction. In addition to VEGF, we and others have reported the angiogenic property of hepatocyte growth factor (HGF) in a rabbit ischemia model. [21][22][23][24] Thus, it is preferable to stimulate angiogenesis by HGF, not only in a normal model but also in other high-risk conditions such as ...

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Assessing an individual's salt intake is necessary for providing guidance with respect to salt restriction. However, the methods that exist for assessing salt intake have both merits and limitations. Therefore, the evaluation methods should be selected for their appropriateness to the patients and the environment of the medical facilities. The purpose of the present study was to investigate the validity of a brief self-administered diet-history questionnaire (BDHQ) by comparing the responses with 24-h urinary salt excretion. A total of 136 hypertensive outpatients (54 men and 82 women) were included in this study. All subjects were given the BDHQ and performed 24-h home urine collection. The energy-adjusted salt intake as assessed by the BDHQ was 12.3 (95% confidence interval: 11.8-12.9) g per day, and the urinary salt excretion evaluated by 24-h urinary collection was 9.0 (8.4-9.5) g per day. The energy-adjusted salt intake assessed by the BDHQ correlated significantly with the urinary salt excretion evaluated by 24-h urinary collection (r=0.34, P<0.001). In conclusion, the estimated salt intake evaluated by the BDHQ weakly, but significantly, correlated with 24-h urinary salt excretion. In clinical practice, it seems important to utilize both methods to assess an individual's salt intake in order to provide adequate guidance for salt restriction.

We investigated the long-term trend and variability of urinary salt (sodium chloride) excretion in hypertensive patients. Subjects included 186 hypertensive patients (103 women and 83 men, mean age: 58.5±10.5 years) who underwent 10 successful 24-h home urine collections over a mean observation period of 7.7 years. We measured 24-h urinary salt excretion and blood pressure (BP) sequentially at the time of each collection and monitored the long-term trend and variability of urinary salt excretion. BP significantly decreased from 145±16/85±11 mm Hg to 130±12/70±11 mm Hg and was associated with an increased use of antihypertensive drugs. The 24-h urinary salt excretion also decreased from 9.5±3.6 g per day at the first measurement to 8.5±3.2 g per day at the 10th measurement. Urinary salt excretion during the observation period ranged from a minimum value of 5.2±1.8 g per day to a maximum value of 13.4±3.6 g per day with a coefficient of variation of 29.2±8.1%. When subjects were assigned to a low, medium and high salt group based on the tertiles of the first measurement of urinary salt excretion and the tertiles based on the mean value of 10 measurements during the observation period, only 56.2% remained in the same category, suggesting that a single measurement of urinary salt excretion can only predict long-term urinary salt excretion in approximately half of the individuals. In conclusion, urinary salt excretion shows large variability such that a single measurement may not be sufficient to assess salt intake in individuals.

K-EUSO (KLYPVE-EUSO) is a planned orbital mission aimed at studying ultra-high energy cosmic rays (UHECRs) by detecting fluorescence and Cherenkov light emitted by extensive air showers in the nocturnal atmosphere of Earth in the ultraviolet (UV) range. The observatory is being developed within the JEM-EUSO collaboration and is planned to be deployed on the International Space Station after 2025 and operated for at least two years. The telescope, consisting of ∼105 independent pixels, will allow a spatial resolution of ∼0.6 km on the ground, and, from a 400 km altitude, it will achieve a large and full sky exposure to sample the highest energy range of the UHECR spectrum. We provide a comprehensive review of the current status of the development of the K-EUSO experiment, paying special attention to its hardware parts and expected performance. We demonstrate how results of the K-EUSO mission can complement the achievements of the existing ground-based experiments and push forward the intriguing studies of ultra-high energy cosmic rays, as well as bring new knowledge about other phenomena manifesting themselves in the atmosphere in the UV range.