The relationship between arterial stiffness and maximal oxygen consumption in healthy young adults.

OBJECTIVE: Arterial 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. METHODS: The subjects were 13 men and 10 women with mean age of 22.9 ±â€¯0.7, 23.6 ±â€¯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. RESULTS: VO2max 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). CONCLUSIONS: This study suggests that there is no relationship between arterial stiffness and aerobic capacity in healthy young adults.

Downregulation of Soluble Guanylate Cyclase and Protein Kinase G With Upregulated ROCK2 in the Pulmonary Artery Leads to Thromboxane A2 Sensitization in Monocrotaline-Induced Pulmonary Hypertensive Rats.

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.

Insights into the Vastly Different Effects of Eutectic Solvents on the Stability of Phenolic Compounds.

Eutectic solvents (ESs) have shown stabilizing effects on several molecules. Due to the potential applicability of bioactive compounds, understanding how ESs stabilize them is of great interest in pharmaceutical and related fields. Here, among various ESs, CTU, which comprise thiourea and choline chloride (ChCl), exerted remarkably high stabilizing effects on various phenolic compounds, whereas CU consisting of urea and ChCl exhibited the opposite effects. Using a potent polyphenol, (-)-epigallocatechin gallate (EGCG), as a model compound, we conducted experimental and in silico studies to unravel the underlying mechanisms of the two very similar ESs for the contrasting effects. The results suggest that ESs can affect with great diversity the stability of EGCG by complicated interactions arising from the unique properties of both ESs and their components.

Applications of different solvents and conditions for differential extraction of lipopolysaccharide in Gram-negative bacteria.

Lipopolysaccharide (LPS) is one of the major components in the outer membrane of Gram-negative bacteria. However, its heterogeneity and variability in different bacteria and differentiation conditions make it difficult to extract all of the structural variants. We designed a solution to improve quality and biological activity of LPS extracted from various bacteria with different types of LPS, as compared to conventional methods. We introduced a quality index as a simple measure of LPS purity in terms of a degree of polysaccharide content detected by absorbance at 204 nm. Further experiments using gel electrophoresis, endotoxin test, and macrophage activation test were performed to evaluate the performance and reliability of a proposed 'T-sol' method and the biological effectiveness and character of the LPS products. We presented that the T-sol method had differential effects on extraction of a RAW 264.7 cell-activating LPS, which was effective in the macrophage activation with similar effects in stimulating the production of TNF-alpha. In conclusion, the T-sol method provides a simple way to improve quality and biological activity of LPS with high yield.

The Kv7 channel activator, retigabine, induces vasorelaxation via an endothelial-independent pathway in male mouse aorta.

PURPOSE: Previous studies have indicated that Kv7 channels have an important role in the regulation of blood vessel reactivity, including in the coronary, renal, and cerebral arteries. The present studies examined whether Kv7 channels regulated vascular reactivity in the mouse aorta and investigated the mechanisms involved in the reactivity. METHODS: Wild-type (WT) male C57BL/6 mice, between 10 and 15 weeks old, were used in this study. The vascular function of the aorta in WT male mice was assessed by using a pin myography system (Model 620; DMT, Denmark). RESULTS: Vasorelaxation by an endothelial-dependent vasodilator, acetylcholine (ACh, 1 nM - 10 µM) and an endothelial-independent vasodilator, sodium nitroprusside (SNP, 1 nM - 10 µM) was induced in the aorta in a dose-dependent manner. Pre-incubation with the nitric oxide synthase inhibitor, L-NAME (100 µM, 20 min), completely abolished ACh-induced vasorelaxation, but did not block retigabine-induced vasorelaxation, which suggested that retigabine caused vasorelaxation in the aorta via smooth muscle activation rather than via endothelial cells. Pre-application of the Kv7 channel blocker, linopirdine (10 µM), resulted in a greater contractile response compared with that induced by vehicle in the aorta. In addition, pre-incubation with linopirdine (10 µM, 20 min) reduced retigabine-induced vasorelaxation (1-50 µM). CONCLUSION: This study has provided evidence that Kv7 channels may play a role in the regulation of aortic blood flow via smooth muscle activation.

Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery.

BACKGROUND: The 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. METHODS: Human bone marrow-derived MSCs (2 × 10(6), 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. RESULTS: Among 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. CONCLUSIONS: In 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.