Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Characterization of Staphylococcus aureus Small Colony Variant (SCV) Clinical Isolates in Zaria, Nigeria

Staphylococcal isolates from specimen submitted to the Medical Microbiology laboratory of Ahmadu Bello University Teaching Hospital, Zaria were collected over a period of 6 months (February-July 2012), characterized by microbiological standard procedures and the S. aureus small colony variant (SCV) isolates were isolated. The antibiotic susceptibility pattern of the isolates was determined by the Kirby-Bauer-CLSI modified disc agar diffusion (DAD) technique. The SCV isolates were assessed for the carriage of four virulence genes; sdrE (putative adhesin) icaA (intracellular adhesin) hlg (hemolysin), Cna (collagen adhesin). A total of 258 non-duplicate staphylococcal isolates made up of 219 (84%) S. aureus and 39 (15%) coagulase-negative staphylococci (coNS) where obtained. A total of 48 (22%) isolates were determined to be S. aureus SCV mainly from wound/abscess (31%). S. aureus SCV isolates were generally resistant to all the nine antibiotics tested with only minimal sensitivity to tigecyclin (10.4%) and ciprofloxacin (18.8%). Statistically, there was no significant difference between the microbial load and the different antibiotics that were used, (P ≥0.05). None of the S. aureus SCV isolates carried the four virulence genes which were tested in this study. The results have therefore proved that S. aureus small colony variant exist in our environment and they are more resistant to most antimicrobial agent than their wild type.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome / 中华医学杂志(英文版)

<p><b>Background</b>Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.</p><p><b>Methods</b>A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.</p><p><b>Results</b>The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).</p><p><b>Conclusions</b>The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.</p>

Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).</p><p><b>RESULTS</b>Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).</p><p><b>CONCLUSIONS</b>Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.</p>

Intraocular soluble intracellular adhesion molecule-1 correlates with subretinal fluid height of diabetic macular edema.

Objective: To investigate the correlations between aqueous concentrations of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and diabetic macular edema (DME). Materials and Methods: VEGF, MCP-1 and sICAM-1 concentrations in aqueous humor samples of 22 patients with DME and 23 patients with cataract of a control group were measured with solid-phase chemiluminescence immunoassay. Results: Aqueous VEGF (89.2 ± 58.5 pg/ml versus 48.5 ± 27.8 pg/ml, P = 0.006), MCP-1 (684.2 ± 423.4 pg/ml versus 432.4 ± 230.4 pg/ml, P = 0.019) and sICAM-1 (3213.8 ± 2581.6 pg/ml versus 260.2 ± 212.2 pg/ml, P < 0.001) all vary significantly between DME group and control group. Maximum height of submacular fluid measured by Optical coherence tomography (OCT) was significantly associated with aqueous sICAM-1 (r = -0.45, P = 0.034). The maximum height of macular thickness measured by OCT was not significantly associated with either VEGF (P = 0.300), MCP-1 (P = 0.320) or sICAM-1 (P = 0.285). Conclusions: Our results suggest that sICAM-1 may majorly contribute to the formation of subretinal fluid in DME patients and imply that MCP-1 and sICAM-1 may be the potential therapy targets, besides VEGF.

Atorvastatin Decreased Toll-Like Receptor 4 Expression and Downstream Signals in Human Endothelial Cells / 中华高血压杂志

Background The impact of statins on inflammation are independent of cholesterol-lowering effect.Recent studies showed that Toll-like receptor 4(TLR4),a mediator of innate immune responses,is involved in the initiation and progression of atherosclerosis.Objective To investigate the effects of atorvastatin on LPS-induced TLR4 expression and downstream signals and to explore the molecular mechanisms of anti-inflammation by statins.Methods Human umbilical vein endothelial cells(HUVEC)were pretreated with atorvastatin(1 or 10 ?mol/L)or NF-?B inhibitor CAPE for 30 min,then incubated by purified LPS for 24 hours.TLR4,ICAM-1 and E-selectin mRNA were measured by RT-PCR;the percentage of TLR4 positive cells were detected by flow cytometry.The activation of NF-?B(p65)were detected by Western blot.Results Atorvastatin(1-10 ?mol/L)prevented LPS-induced increases in TLR4,ICAM-1 and E-selectin expression [TLR4 mRNA(1.24?0.21)vs LPS(1.82?0.27),P

Protective effect of baicalin on inflammatory injury following transient focal cerebral ischemia-reperfusion in rats / 中国药理学与毒理学杂志

AIM To investigate if the protective effect of baicalin on cerebral injury induced by transient focal ischemia is related to modulation of expressions of inflammatory cytokines or adhesive molecules. METHODS Transient focal cerebral ischemia injury model in rats was induced by occlusion of the right middle cerebral artery for 2 h, followed by 24 h reperfusion. The infarct volume and neurological deficit were determined by TTC staining and the scoring method of Longa et al. The expression of intracellular adhesion molecule-1 (ICAM-1), neutrophils infiltration, and myeloperoxidase (MPO) activity in brain were measured by immunohistochemistry, hematoxylin-eosin staining, and spectrophotometer, respectively. Semiquantitative RT-PCR was employed to assess the expression of inducible nitric oxide synthase (iNOS) mRNA. The level of interleukin-1 (IL-1) in brain was assayed by radioimmunoassay. The expression of nuclear factor-κB (NF-κB) protein was evaluated by Western blot. RESULTS After transient cerebral ischemia, MPO activity and the expression of ICAM-1 in the periphery of ischemic cortex were significantly increased. Increase in iNOS mRNA and NF-κB protein expression was also shown in the ischemic area. Treatment with baicalin markedly reduced brain infarct volume and neurological deficit induced by ischemic insult, inhibited MPO activity, inflammatory cell infiltration, as well as expression of ICAM-1, iNOS and NF-κB, and decreased IL-1 level. CONCLUSION Baicalin may play a protective effect on cerebral ischemic injury through inhibiting the expression and release of the inflammatory mediators after cerebral ischemia.

Soluble intracellular adhesion molecule-1 concentrations in the serum and peritoneal fluid from endometriosis patients / 医学研究生学报

Objectives:To investigate the level of soluble intracellular adhesion molecule 1 (sICAM 1) concentrations in the serum and peritoneal fluid from the patients with or without endometriosis.To discuss the relationship within sICAM 1 and pelvic endometriosis. Methods:35 serum and 30 peritoneal fluid of patients with endometriosis (test group) and 26 serum and 4 peritoneal fluid without endometriosis (control group) were studied.Soluble intracellular adhesion molecule 1 levels were detected by an enzyme linked immunoassay(ELISA).The results were analysed by T test. Results: The serum concentration of sICAM 1 was significantly higher in test group than controll group. However,There was no significant difference in between two groups. Conclusions: These results suggest that sICAM 1 could play some role in the persistence of endometriotic lesions.

Experimental study on correlation of ICAM-1 and fat metabolism with steroid femur head necrosis / 解放军医学杂志

Objective To study the intercellular adhesion molecule-1(ICAM-1)and fat metabolism in the contribution of the incidence of steroid avascular necrosis of femoral head(ANFH).Methods 32 New Zealand rabbits were randomly divided into two groups:animals in experiment group(n=24)were given an injection of hydrocortisone acetate(8.0mg/kg)two times per week,and animals in control group(n=8)were given an injection with the same volume of normal saline.Serum total cholesterol(TC),triglyceride(TG)and ICAM-1 were quantitated before and 2,4,6,8 weeks after the treatment.2,4,6 and 8 weeks after treatment,6 animals of the experiment group and 2 of the control group were randomly chosen and sacrificed.ICAM-1 expression in soft tissue around hip was determined immunohistochemically,and pathohistological changes in femoral head were observed by light microscopy.Results Serum TC and TG levels of the animals in experimental group were significantly higher than those before treatment and those in control group in the 6th week after treatment(P

The expression of tumor necrosis factor-alpha and intracellular adhesion molecular-1 in cerebral tissue after experimental intracerebral hemorrhage in rats / 临床神经病学杂志

Objective To investigate the expression of tumor necrosis factor-?(TNF-?) and intracellular adhesion molecular-1(ICAM-1) in brain tissue after experimental intracerebral hemorrhage in rats.Methods Experimental intracerebral hemorrhage model was maded by injection autologous blood using stereotactic method. The expression of TNF-? and ICAM-1 in cerebral tissues at different time were detected by using immunohistochemitry techniques.Results TNF-? expression raised obviously at 6 h and peaked at 48 h.ICAM-1 expression raised obviously at 12 h and peaked at 72 h.There was obvious difference between each intracerebral hemorrhage group and controls(all P

EXPERIMENTAL STUDY ON THE EFFECT OF REMIFENTANIL ON THE EXPRESSION OF ADHENSIVE FACTORS IN LUNG INJURY IN RATS / 解放军医学杂志

To determine the effects of Remifentanil on the expression of adhesive factors during acute lung injury, we used immunohistochemistry and reverse transcription polymerase chain reaction (RT PCR) technics to measure the expression levels of ICAM 1, and P Selectin in the lung in a rat model of hemorrhagic shock. We duplicated modified Wigger hemorrhagic shock model in healthy SD rats. The rats were divided into three groups: control group, resuscitation group, resuscitation and drug using group. The positive ratios of ICAM 1 and P Selectin in the lungs at different time points, namely preshock, shock, resuscitation 2 hours, and resuscitation 4 hours were determined. There were 6 rats in each group and each time point. The degree of pulmonary injury in the drug using group was less than that in other two groups. Resuscitation with lactated Ringer's solution led to most serious injury in the resuscitation group. In drug using group, the expression of ICAM 1 and P Selectin was far less than that in the other two groups ( P