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Fulltext Leptin increases blood pressure and markers of endothelial activation during pregnancy in rats

Ibrahim HS, Omar E, Froemming GR, Singh HJ

Biomed Res Int, 2013;2013:298401.
PMID: 24167814 DOI: 10.1155/2013/298401

Raised leptin levels have been reported in the placentae and serum of women with elevated blood pressure and proteinuria during pregnancy. The role of leptin in this however remains unknown. This study investigates the effect of leptin administration on systolic blood pressure (SBP) and proteinuria and serum markers of endothelial activation during pregnancy in Sprague Dawley rats. From day 1 of pregnancy, 24 rats were randomised into those given either saline (group 1) or leptin at 60 or 120 μ g/kg/body weight/day (groups 2 and 3 resp.). SBP was measured every 5 days and 24-h urinary protein was measured at days 0 and 20 of pregnancy. Animals were euthanised on day 20 of pregnancy, and serum was collected for estimation of E-selectin and ICAM-1. Compared to group 1, SBP during the latter part of the pregnancy was significantly higher in the leptin-treated group (P < 0.01). Urinary protein excretion, serum E-selectin, and ICAM-1 were significantly higher in leptin-treated rats (P < 0.05). It seems that leptin administration to normotensive Sprague Dawley rats during pregnancy significantly increases SBP, urinary protein excretion, and markers of endothelial activation. However, further studies are required to examine the underlying mechanism responsible for this and its relevance to preeclampsia in humans.

Matched MeSH terms: E-Selectin/blood
ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats

Ibrahim HS, Froemming GR, Omar E, Singh HJ

Reprod Toxicol, 2014 Nov;49:155-61.
PMID: 25205467 DOI: 10.1016/j.reprotox.2014.08.006

This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure (SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injection of either saline, or leptin, or leptin plus xanthenone (ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; also their gene expressions were determined in the kidney and aorta respectively. Compared to control, SBP was higher in the leptin-only treated group (P<0.001) and lower in rats treated with xanthenone alone (P<0.01). Proteinuria, markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P<0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P<0.05). It seems, leptin administration during pregnancy significantly increases SBP, proteinuria, endothelial activation, but decreases ACE2 level and expression. These effects are prevented by concurrent administration of xanthenone.

Matched MeSH terms: E-Selectin/blood
Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin

Nawawi H, Osman NS, Annuar R, Khalid BA, Yusoff K

Atherosclerosis, 2003 Aug;169(2):283-91.
PMID: 12921980

Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.

Matched MeSH terms: E-Selectin/blood
Fulltext Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study

Rahman T, Hamzan NS, Mokhsin A, Rahmat R, Ibrahim ZO, Razali R, et al.

Lipids Health Dis, 2017 Apr 24;16(1):81.
PMID: 28438163 DOI: 10.1186/s12944-017-0470-1

BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers.
METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis.
RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p E-selectin were higher in FH compared to NC (mean ± SD = 947 ± 742 vs 655 ± 191 ng/mL, p 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p

Matched MeSH terms: E-Selectin/blood
Fulltext Effects of exchanging carbohydrate or monounsaturated fat with saturated fat on inflammatory and thrombogenic responses in subjects with abdominal obesity: A randomized controlled trial

Teng KT, Chang LF, Vethakkan SR, Nesaretnam K, Sanders TAB

Clin Nutr, 2017 10;36(5):1250-1258.
PMID: 27642057 DOI: 10.1016/j.clnu.2016.08.026

BACKGROUND & AIMS: Modification of the amount and type of dietary fat has diverse effects on cardiovascular risk.
METHODS: We recruited 54 abdominally obese subjects to participate in a prospective cross-over design, single-blind trial comparing isocaloric 2000 kcal MUFA or carbohydrate-enriched diet with SFA-enriched diet (control). The control diet consisted of 15E% protein, 53E% carbohydrate and 32E% fat (12E% SFA, 13E% MUFA). A total of ∼7E% of MUFA or refined carbohydrate was exchanged with SFA in the MUFA-rich and carbohydrate-rich diets respectively for 6-weeks. Blood samples were collected at fasting upon trial commencement and at week-5 and 6 of each dietary-intervention phase to measure levels of cytokines (IL-6, IL-1β), C-reactive protein (CRP), thrombogenic markers (E-selectin, PAI-1, D-dimer) and lipid subfractions. Radial pulse wave analysis and a 6-h postprandial mixed meal challenge were carried out at week-6 of each dietary intervention. Blood samples were collected at fasting, 15 and 30 min and hourly intervals thereafter till 6 h after a mixed meal challenge (muffin and milkshake) with SFA or MUFA (872.5 kcal, 50 g fat, 88 g carbohydrates) or CARB (881.3 kcal, 20 g fat, 158 g carbohydrates)- enrichment corresponding to the background diets.
RESULTS: No significant differences in fasting inflammatory and thrombogenic factors were noted between diets (P > 0.05). CARB meal was found to increase plasma IL-6 whereas MUFA meal elevated plasma D-dimer postprandially compared with SAFA meal (P

Matched MeSH terms: E-Selectin/blood