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Reproducibility of laser Doppler fluximetry and the process of iontophoresis in assessing microvascular endothelial function using low current strength

Al-Tahami BA, Yvonne-Tee GB, Halim AS, Ismail AA, Rasool AH

Methods Find Exp Clin Pharmacol, 2010 Apr;32(3):181-5.
PMID: 20448860 DOI: 10.1358/mf.2010.32.3.1423887

Iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) combined with laser Doppler fluximetry (LDF) is a tool used to determine microvascular endothelial function. Our aim was to study the reproducibility of different parameters of this technique using iontophoresis with low current strength on the forearm skin of healthy subjects. Baseline skin perfusion was done before application of five current pulses with 1 min of current-free interval. Current strength of 0.007 mA, current density of 0.01 mA/cm(2) and charge density of 6 mC/cm(2) were used, along with 1% ACh and 1% SNP. The absolute maximum change in perfusion (max), percent change in perfusion (% change), peak change in perfusion (peak) and area under the curve during iontophoresis (AUC) at the anodal and cathodal leads were recorded. Measurements were performed in three sessions for 2 days. The coefficient of variation (CV) was calculated for each parameter. Among the parameters studied, maximum change in perfusion and peak flux were the most reproducible parameters.

Matched MeSH terms: Microvessels/metabolism
Impaired microvascular endothelial function in relatively young obese humans is associated with altered metabolic and inflammatory markers

Al-Tahami BA, Bee YT, Ismail AA, Rasool AH

Clin. Hemorheol. Microcirc., 2011;47(2):87-97.
PMID: 21339629 DOI: 10.3233/CH-2010-1370

INTRODUCTION: This study aims to assess microvascular endothelial function in obese compared to age matched lean controls. Serum lipid profile, fasting glucose, high sensitivity C-reactive protein (hs-CRP) and adiponectin levels were also determined.
METHODS: This cross-sectional study involved 36 healthy lean and 36 obese subjects. Microvascular endothelial function was assessed using Laser Doppler fluximetry and iontophoresis with acetylcholine and sodium nitroprusside.
RESULTS: Mean age of subjects was 26.54 ± 0.60 years. Obese subjects had higher systolic (118.8 ± 1.5 vs 105.7 ± 2.0 mmHg, p < 0.001) and diastolic blood pressure (71.61 ± 1.35 vs 64.53 ± 1.40 mmHg, p = 0.001), higher triglyceride (1.35 ± 0.13 vs 0.79 ± 0.05 mmol/l, p < 0.001), lower high density lipoprotein cholesterol (HDL-C) (1.43 ± 0.04 vs 1.62 ± 0.05 mmol/l, p = 0.003), higher hs-CRP (11.58 ± 1.88 vs 1.88 ± 0.35 mg/l, p < 0.001), and lower adiponectin levels (8.80 ± 0.43 vs 25.93 ± 0.40 μg/ml, p < 0.001) compared to lean subjects. Endothelial dependent vasodilatation was lower in obese compared to lean subjects (40.53 ± 6.59 vs 71.03 ± 7.13 AU, p = 0.001).
CONCLUSION: Microvascular endothelial function is reduced in obese compared to age matched controls. This is associated with higher BP, triglyceride and lower HDL-C and adiponectin levels in obese group.
Study site: not mentioned

Matched MeSH terms: Microvessels/metabolism*
Fulltext Escherichia coli K1 utilizes host macropinocytic pathways for invasion of brain microvascular endothelial cells

Loh LN, McCarthy EMC, Narang P, Khan NA, Ward TH

Traffic, 2017 11;18(11):733-746.
PMID: 28799243 DOI: 10.1111/tra.12508

Eukaryotic cells utilize multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here, we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we demonstrate that small Rho GTPases and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin-mediated endocytosis appears to play an indirect role in E. coli K1 uptake. The data suggest that the bacteria effect a complex interplay between the Rho GTPases to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.

Matched MeSH terms: Microvessels/metabolism
Impaired microvascular endothelial function in vitamin D-deficient diabetic nephropathy patients

Munisamy S, Kamaliah MD, Suhaidarwani AH, Zahiruddin WM, Rasool AH

J Cardiovasc Med (Hagerstown), 2013 Jun;14(6):466-71.
PMID: 22964652 DOI: 10.2459/JCM.0b013e3283590d3d

AIMS: This study aims to compare microvascular endothelial function between vitamin D-deficient and nondeficient groups of patients with diabetic nephropathy. Serum levels of the inflammatory marker high-sensitivity C-reactive protein (hsCRP) were also measured.
METHODS: This prospective cross-sectional study involved 70 patients with diabetic nephropathy; 40 were categorized into the group with nondeficient serum 25-hydroxyvitamin D levels [25(OH)D >50 nmol/l], whereas 30 patients were categorized to the group with deficient serum 25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and sodium nitroprusside were used to determine endothelium-dependent and independent vasodilatation.
RESULTS: Mean age of patients was 56.7 ± 3.8 years; 50 were men, whereas 20 were women. Mean serum 25(OH)D in the vitamin D-nondeficient group was 69.4 ± 2.9 nmol/l; the level in the vitamin D-deficient group was 42.1 ± 1.3 nmol/l, P < 0.001. Endothelium-dependent vasodilatation was lower in the vitamin D-deficient group compared with the vitamin D-nondeficient group (23.6 ± 2.7 versus 37.3 ± 3.8 arbitrary units, P = 0.004). No significant differences were observed between the two groups in their hsCRP levels, mean age, estimated glomerular filtration rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and glycosylated haemoglobin.
CONCLUSION: Microvascular endothelial function was significantly reduced in diabetic nephropathy patients with deficient vitamin D levels compared with those with nondeficient levels.

Matched MeSH terms: Microvessels/metabolism
Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors

Jaafar H, Abdullah S, Murtey MD, Idris FM

Asian Pac J Cancer Prev, 2012;13(8):3857-62.
PMID: 23098483

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

Matched MeSH terms: Microvessels/metabolism
Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary institution in the East Coast of Malaysia with a focus on tumor angiogenesis

Ch'ng ES, Tuan Sharif SE, Jaafar H

Asian Pac J Cancer Prev, 2012;13(9):4445-52.
PMID: 23167359

BACKGROUND: Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors.
METHODS: Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density.
RESULTS: At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05).
CONCLUSIONS: Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.

Matched MeSH terms: Microvessels/metabolism
Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells

Wong PF, Jamal J, Tong KL, Khor ES, Yeap CE, Jong HL, et al.

Microvasc Res, 2017 11;114:26-33.
PMID: 28595801 DOI: 10.1016/j.mvr.2017.06.002

miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20ng/ml) of tumor necrosis factor alpha (TNF-α) for 15days. In parallel, HMVEC-Ls were grown and routinely passaged until the onset of replicative senescence (RS). Differential expression analysis following miRNA microarray profiling revealed an overlapped of eight deregulated miRNAs in both the miRNA profiles of RS and TNF-α-induced premature senescence cells. Amongst the deregulated miRNAs were members of the miR 17-92 cluster which are known regulators of angiogenesis. The role of hsa-miR-20b in TNF-α-induced premature senescence, a paralog member of the miR 17-92 cluster, was further investigated. Biotin-labeled hsa-miR-20b captured the enriched transcripts of retinoblastoma-like 1 (RBL1), indicating that RBL1 is a target of hsa-miR-20b. Knockdown of hsa-miR-20b attenuated premature senescence in the TNF-α-treated HMVEC-Ls as evidenced by increased cell proliferation, increased RBL1 mRNA expression level but decreased protein expression of p16INK4a, a cellular senescence marker. These findings provide an early insight into the role of hsa-miR-20b in endothelial senescence.

Matched MeSH terms: Microvessels/metabolism
Fulltext Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury

Barber BE, Grigg MJ, Piera KA, William T, Cooper DJ, Plewes K, et al.

Emerg Microbes Infect, 2018 Jun 06;7(1):106.
PMID: 29872039 DOI: 10.1038/s41426-018-0105-2

Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel-Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.

Matched MeSH terms: Microvessels/metabolism