Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients.

BACKGROUND: This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes. METHODS AND RESULTS: Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating. CONCLUSIONS: These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.

Serum 25-hydroxy vitamin D levels in essential hypertension.

Vitamin D may have prognostic value in hypertension patients and, in addition to conventional biomarkers, could be a valuable tool for disease management. The aim of this study was to assess the association of vitamin D status in patients with essential hypertension and to evaluate its prognostic utility. Forty-eight consecutive patients (40 Caucasian and 8 Asian) aged between 30 and 80 years (mean 61.5, range 34-84 years), were enrolled in the study. The main exclusion criteria were age less than 18 years, kidney failure, onco-hematologic disease, hypo-hyperparathyroidism, osteoporosis, treatment with bisphosphonate or 25(OH) vitamin D supplementation. Of the 48 patients included in the study, hyperlipidemia was described in 28, diabetes type 2 in 8, and ischemic heart disease in 14. Serum electrolytes, calcium, sodium, and potassium concentrations were within normal range. Low 25(OH) vitamin D levels inversely correlated with essential hypertension values (p less than 0.001) were considered extremely significant. The determination of 25(OH) vitamin D levels in patients with essential hypertension could improve the research for possible underlying conditions, which should be managed meticulously according to current guidelines.

Xuezhikang reduced arterial stiffness in patients with essential hypertension: a preliminary study.

This study aimed to test the effects of xuezhikang, a cholestin extract that contains statin-like components, on arterial stiffness in patients with essential hypertension. One hundred hypertensive patients from the Chinese PLA General Hospital were randomly allocated to receive xuezhikang (1200 mg/day, orally) or placebo (same capsules containing only pharmaceutical excipients). Physical examination outcomes, lipid profile, high sensitivity C-reactive protein (hs-CRP) levels, matrix metalloproteinases-9 (MMP-9) levels, and arterial outcomes, including stiffness parameter (ß), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AI), and one-point pulse wave velocity (PWVß) were obtained at baseline and after 6 months of the intervention. Xuezhikang significantly reduced ß (8.4±3.1 vs 6.8±2.1, P=0.007), Ep (122.8±43.9 vs 100.7±33.2, P=0.009), PWVß (6.7±1.2 vs 6.1±1.0, P=0.013), low-density lipoprotein cholesterol (3.4±0.6 vs 2.9±0.5, P=0.001), hs-CRP [2.1 (0.4-10.0) vs 1.4 (0.3-4.1), P=0.020], and MMP-9 (17.2±2.4 vs 12.7±3.8, P <0.001) compared to baseline. The placebo had no effect on these parameters. The changes of PWVß in the xuezhikang group was significantly associated with the changes of hs-CRP and MMP-9 (r=0.144, P=0.043; r=0.278, P=0.030, respectively) but not with lipid profile changes. Our research showed xuezhikang can improve the parameters of arterial stiffness in hypertensive patients, and its effect was independent of lipid lowering.

The Impact of Supplementation with Folic Acid on Homocysteine Concentration and Selected Lipoprotein Parameters in Patients with Primary Hypertension.

The aim of the study was the assessment of the impact of supplementation with folic acid on the concentration of homocysteine, total cholesterol (TC), HDL- and LDL-cholesterol, triglycerides (TG), apoprotein AI (apoAI) and apoprotein B (apoB) in patients suffering from primary hypertension. The examined group comprised 42 patients suffering from primary hypertension. All examined patients underwent laboratory tests as follows: concentration of homocysteine, folic acid, TC, LDL-cholesterol, HDL-cholesterol, TG, apoAI and apoB. All patients were orally administered with 15 mg of folic acid per day for 45 d. After this period, all laboratory tests were repeated. Homocysteine concentration was measured by the FPIA method, concentrations of apoAI and apoB were measured by the nephelometric method, and other parameters with routine methods. After administration of 15 mg of folic acid to patients with primary hypertension, a considerable decrease in the concentration of homocysteine was observed in parallel with a substantive growth of HDL-cholesterol, as well as apoprotein AI concentrations and a reduction of the apoprotein B concentration. Results of statistical analysis indicated a significant correlation between the decline in homocysteine concentration and the increase in HDL-cholesterol concentration, as well as between the increase of folic acid concentration and the increase in apoAI concentration in patients following the intake of folic acid. The drop in homocysteine concentration through the supplementation with folic acid can cause quantitative changes in the lipid and lipoprotein parameters which, in consequence, may lead to the mitigation of risk concerning the development of atherosclerosis.

Xuezhikang reduced arterial stiffness in patients with essential hypertension: a preliminary study

This study aimed to test the effects of xuezhikang, a cholestin extract that contains statin-like components, on arterial stiffness in patients with essential hypertension. One hundred hypertensive patients from the Chinese PLA General Hospital were randomly allocated to receive xuezhikang (1200 mg/day, orally) or placebo (same capsules containing only pharmaceutical excipients). Physical examination outcomes, lipid profile, high sensitivity C-reactive protein (hs-CRP) levels, matrix metalloproteinases-9 (MMP-9) levels, and arterial outcomes, including stiffness parameter (β), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AI), and one-point pulse wave velocity (PWVβ) were obtained at baseline and after 6 months of the intervention. Xuezhikang significantly reduced β (8.4±3.1 vs 6.8±2.1, P=0.007), Ep (122.8±43.9 vs 100.7±33.2, P=0.009), PWVβ (6.7±1.2 vs 6.1±1.0, P=0.013), low-density lipoprotein cholesterol (3.4±0.6 vs 2.9±0.5, P=0.001), hs-CRP [2.1 (0.4-10.0) vs 1.4 (0.3-4.1), P=0.020], and MMP-9 (17.2±2.4 vs 12.7±3.8, P <0.001) compared to baseline. The placebo had no effect on these parameters. The changes of PWVβ in the xuezhikang group was significantly associated with the changes of hs-CRP and MMP-9 (r=0.144, P=0.043; r=0.278, P=0.030, respectively) but not with lipid profile changes. Our research showed xuezhikang can improve the parameters of arterial stiffness in hypertensive patients, and its effect was independent of lipid lowering.

A Targeted Metabolomics MRM-MS Study on Identifying Potential Hypertension Biomarkers in Human Plasma and Evaluating Acupuncture Effects.

The critical role of metabolic abnormality in hypertension is increasingly recognized, but its biomarkers are not clearly identified. In this study, 47 chemical compounds recorded by literature were employed as target metabolites of essential hypertension (EH). We detected their content in the plasma of EH patients and healthy subjects by using the Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). After screening the most altered compounds, acupuncture was used to treat patients for 3 months and these plasma metabolites were tested again. The results showed that oleic acid (OA) and myoinositol (MI) were the most important differential metabolites between the hypertensive plasma and the healthy plasma. They were also closely correlated with 24-hour blood pressure and nocturnal dipping. Moreover, plasma OA and MI could be restored to normal levels by acupuncture, accompanying with reduction of 24-hour systolic and diastolic blood pressure [from 145.10 ± 9.28 mm Hg to 140.70 ± 9.59 mm Hg (P < 0.0001), and 88.35 ± 7.92 mm Hg to 85.86 ± 7.95 mm Hg (P = 0.0024), respectively] and improvement of circadian blood pressure rhythm. This study demonstrated that plasma OA and MI were potential hypertension biomarkers and they could be used to preliminarily assess the treating effects such as acupuncture.