BackgroundThe efficacy of mesenchymal stem cell (MSC) transplantation in ischemic stroke might depend on the timing of administration. We investigated the optimal time point of MSC transplantation. After MSC treatment, we also investigated the expression of matrix metalloproteinases (MMPs), which play a role in vascular and tissue remodeling.MethodsHuman bone marrow-derived MSCs (2 × 106, passage 5) were administrated intravenously after permanent middle cerebral artery occlusion (MCAO) was induced in male Sprague-Dawley rats. First, we determined the time point of MSC transplantation that led to maximal neurological recovery at 1 h, 1 day, and 3 days after MCAO. Next, we measured activity of MMP-2 and MMP-9, neurological recovery, infarction volume, and vascular density after transplanting MSCs at the time that led to maximal neurological recovery.ResultsAmong the MSC-transplanted rats, those of the MSC 1-hour group showed maximal recovery in the rotarod test (P = 0.023) and the Longa score (P = 0.018). MMP-2 activity at 1 day after MCAO in the MSC 1-hour group was significantly higher than that in the control group (P = 0.002), but MMP-9 activity was not distinct. The MSC 1-hour group also showed smaller infarction volume and higher vascular density than did the control group.ConclusionsIn a permanent model of rodent MCAO, very early transplantation of human MSCs (1 h after MCAO) produced greater neurological recovery and decreased infraction volume. The elevation of MMP-2 activity and the increase in vascular density after MSC treatment suggest that MSCs might help promote angiogenesis and lead to neurological improvement during the recovery phase after ischemic stroke.

Thromboxane A2 (TXA2) promotes various physiological responses including pulmonary artery (PA) contraction, and pathophysiological implications have been suggested in cardiovascular diseases including pulmonary hypertension. Here, we investigated the role of TXA2 receptor (TP)-mediated signaling in the pathophysiology of pulmonary arterial hypertension (PAH). The sensitivity of PA to the contractile agonist could be set by relaxing signals such as the nitric oxide (NO), soluble guanylate cyclase (sGC), and cGMP-dependent kinase (PKG) pathways. Changes in the TP agonist (U46619)-induced PA contraction and its modulation by NO/cGMP signaling were analyzed in a monocrotaline-induced PAH rat model (PAH-MCT). In the myograph study, PA from PAH-MCT showed higher responsiveness to U46619, that is decreased EC50. Immunoblot analysis revealed a lower expression of eNOS, sGC, and PKG, while there was a higher expression of RhoA-dependent kinase 2 (ROCK2) in the PA from PAH-MCT than in the control. In PAH-MCT, the higher sensitivity to U46619 was reversed by 8-Br-cGMP, a membrane-permeable cGMP analog, but not by the NO donor, sodium nitroprusside (SNP 30 μM). In contrast, in the control PA, inhibition of sGC by its inhibitor (1H− [1,2,4] oxadiazolo [4,3−a] quinoxalin-1-one (ODQ), 10 μM) lowered the threshold of U46619-induced contraction. In the presence of ODQ, SNP treatment had no effect whereas the addition of 8-Br-cGMP lowered the sensitivity to U46619. The inhibition of ROCK by Y-27632 attenuated the sensitivity to U46619 in both control and PAH-MCT. The study suggests that the attenuation of NO/cGMP signaling and the upregulation of ROCK2 increase the sensitivity to TXA2 in the PAH animal, which might have pathophysiological implications in patients with PAH.

ObjectiveArterial stiffness is associated with an increased risk of cardiovascular diseases in various populations. There was little research on the relationship between arterial stiffness and maximal aerobic capacity (VO2max) in healthy young adults. The aim of this study was to investigate the relationship between VO2max and arterial stiffness in young adults.MethodsThe subjects were 13 men and 10 women with mean age of 22.9 ± 0.7, 23.6 ± 0.4 years, respectively. Height, weight, body mass index, body fat (%), waist to hip ratio, total/high density lipoprotein (HDL)/low density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, blood pressure, heart rate, glycated hemoglobin and blood lactate were measured. In addition, peripheral arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (baPWV) and VO2max was determined using graded exercise test.ResultsVO2max had no significant correlation with baPWV (r = 0.2, p = 0.2). Total cholesterol correlated significantly to variables such as HDL (r = 0.6, p = 0.0015) and LDL cholesterol (r = −0.6, p = 0.0018). VO2max had a significant association with triglyceride (r = −0.5, p = 0.0033).ConclusionsThis study suggests that there is no relationship between arterial stiffness and aerobic capacity in healthy young adults.

The purpose of this study was to compare the differences in the expression of FNDC5 and irisin according to the intensity of exercise and to determine the most effective exercise intensity for the expression of FNDC5 and irisin immediately after acute exercise. METHODS: Studies were conducted using healthy male wild-type C57BLKS/J-m+/m+ mice aged 13-15 weeks. Each group of the mice was randomly assigned to four different groups: control, low intensity (10 m/min, inclination 0°, 25 minutes), moderate intensity (15 m/min, inclination 0°, 25 minutes), high intensity (20 m/min, inclination 0°, 25 minutes). After each exercise, we examined the acute response of irisin and signaling proteins related to irisin. RESULTS: The results showed that mRNA expression of FNDC5 tended to increase with increasing exercise intensity, and there was a significant difference between the control group and the moderate intensity exercise group. However, there was no significant difference in protein expression of FNDC5 and irisin in all groups. CONCLUSIONS: In conclusion, the acute aerobic exercise did not increase protein expression of FNDC5 and irisin even though aerobic exercise increased the mRNA expression of FNDC5. This results indicated that the 30-minute acute aerobic exercise was not enough stimulation to allow transfer from mRNA expression of FNDC5 to protein expression of FNDC5 and irisin.

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