Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat thoracic aorta

Otsuka, Aiko; Azuma, Kosuke; Iesaki, Takafumi; Sato, Fumiya; Hirose, Takahisa; Shimizu, Tomoaki; Tanaka, Yasushi; Daida, Hiroyuki; Kawamori, Ryuzo; Watada, Hirotaka

doi:10.1007/s00125-005-0005-6

Cited by 76 publications

(54 citation statements)

References 30 publications

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“…Monocyte adhesion to the thoracic aorta was quantified by en face immunohistochemistry, as described previously [14][15][16][17][18]. Briefly, rats (n=6 from each group) were killed under anaesthesia induced by i.p.…”

Section: En Face Immunohistochemistry Of Endothelial Surfacementioning

confidence: 99%

“…Specimens were viewed under a microscope (E800; Nikon, Tokyo, Japan) as described previously [14]. The density of CD68-immunopositive cells in the thoracic aorta was calculated by examiners blinded to the treatment regimen, as described previously [14,15]. ICAM-1 and VCAM-1 abundance was also evaluated by enface immunostaining using the thoracic aorta of each group (ICAM-1, n=6 each; VCAM-1, n=6 each).…”

Section: En Face Immunohistochemistry Of Endothelial Surfacementioning

confidence: 99%

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Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta

et al. 2011

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Aims/hypothesis Severe hypoglycaemia associated with diabetes management is a potential risk for cardiovascular diseases. However, the effect and mechanism of hypoglycaemia on the progression of atherosclerosis remains largely unknown. As a first step towards elucidating the above, we investigated the effect of hypoglycaemia on monocyte-endothelial interaction. Methods Insulin was injected intraperitoneally once every 3 days for 5 weeks in Goto-Kakizaki rats, a non-obese rat model of type 2 diabetes. We counted the number of monocytes adherent to the endothelium of thoracic aorta as an index of early atherosclerogenesis. Cultured HUVEC were used to investigate the mechanism of action. Results Insulin treatment increased the number of monocytes adherent to the vascular endothelium. This increase was abrogated by injection of glucose with insulin. Amosulalol, an α-1 and β-adrenoreceptor antagonist, suppressed monocyte adhesion to endothelium and levels of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in the endothelial surface, which had been enhanced by insulin-induced hypoglycaemia. In HUVEC, adrenaline (epinephrine) significantly increased nuclear translocation of nuclear factor-κB (NF-κB) p65 and levels of adhesion molecules, effects that were abrogated following addition of SQ22536, a specific adenyl cyclase inhibitor. Conclusions/interpretation Our data indicate that repetitive hypoglycaemia induced by insulin enhanced monocyte adhesion to endothelial cells in Goto-Kakizaki rat aorta through enhanced adrenaline activity and that the latter stimulated intracellular cAMP, leading to nuclear translocation of NF-κB with subsequent production of adhesion molecules in endothelial cells.

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Section: En Face Immunohistochemistry Of Endothelial Surfacementioning

confidence: 99%

Section: En Face Immunohistochemistry Of Endothelial Surfacementioning

confidence: 99%

Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta

et al. 2011

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“…At the end of the treatment, monocyte adhesion to the thoracic aorta was quantified by NEMOes, as described previously [17][18][19][20][21]. Briefly, rats were sacrificed under anesthesia induced by intraperitoneal injection of sodium pentobarbital (50 mg/kg; Nembutal, Abbott Laboratories, Abbott Park, IL).…”

Section: Nemoesmentioning

confidence: 99%

“…This method provides a clear focused image of the entire endothelial surface, enabling quantitation of monocytes that adhere to a specific region of rat thoracic aorta after immunostaining for the monocyte/macrophage-specific protein, CD68 [17][18][19][20][21]. Here, we used this method to investigate the effect of ARB on monocyte adhesion to endothelial cells in spontaneously hypertensive rats (SHR).…”

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confidence: 99%

Angiotensin II Type 1 Receptor Blocker Reduces Monocyte Adhesion to Endothelial Cells in Spontaneously Hypertensive Rats

et al. 2007

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Abstract. Monocyte adhesion to arterial endothelial cells is the initial step in atherosclerosis. Whereas angiotensin II is known to elicit leukocyte adhesion, it is not clear whether blockade of the angiotensin II receptor signaling reduces monocyte adhesion to endothelial cells beyond its antihypertensive action. This study compared the effect of two different antihypertensive drugs on monocyte adhesion to thoracic aorta endothelium in spontaneously hypertensive rats (SHR): the angiotensin II receptor blocker, valsartan (20 mg · kg -1 · day -1 ) and the vasodilator, hydralazine (0.75 mg · kg -1 · day -1 ). The effects were quantitated in vivo using an enface method that optimizes the observation of endothelial surfaces after immunohistochemical staining for CD68. Both agents significantly and comparably reduced blood pressure over 4-week treatment course. Both valsartan and hydralazine profoundly reduced monocyte adhesion compared with nontreated controls, with valsartan having a modestly more reductive effect. Both agents also reduced the intima and medial thickening with valsartan reducing the mean thickness modestly more than hydralazine. Our data confirms that the reduction of blood pressure is effective method to reduce monocyte adhesion. Also, our date demonstrates that valsartan has a modest beneficial effect on monocyte adhesion to endothelial cells and arterial intima-medial vessel thickening beyond its action as an antihypertensive agent.

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“…The effects of high glucose on gene expression and protein levels have been described in various cell-types in vitro [13][14][15][16][17]. However, few studies have addressed effects of hyperglycaemia in vivo [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Short-term hyperglycaemia causes non-reversible changes in arterial gene expression in a fully ‘switchable’ in vivo mouse model of diabetes

Zervou

Wang

Laiho³

et al. 2010

Diabetologia

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Aims/hypothesis Irreversible arterial damage due to early effects of hypo-or hyperglycaemia could account for the limited success of glucose-lowering treatments in preventing cardiovascular disease (CVD) events. We hypothesised that even brief hypo-or hyperglycaemia could adversely affect arterial gene expression and that these changes, moreover, might not be fully reversible. Methods By controlled activation of a 'switchable' c-Myc transgene in beta cells, adult pIns-c-MycER TAM mice were rendered transiently hypo-and then hyperglycaemic, after which they were allowed to recover for up to 3 months. Immediate and sequential changes in aortic global gene expression from normal glycaemia through hypo-and hyperglycaemia to recovery were assessed. Results Gene expression was compared with that of normoglycaemic transgenic and tamoxifen-treated wildtype controls. Overall, expression of 95 genes was significantly affected by moderate hypoglycaemia (glucose down to 2.5 mmol/l), whereas over 769 genes were affected by hyperglycaemia. Genes and pathways activated included several involved in atherogenic processes, such as inflammation and arterial calcification. Although expression of many genes recovered to initial pre-exposure levels when hyperglycaemia was corrected (74.9%), in one in four genes this did not occur. Quantitative reverse transcriptase PCR and immunohistochemistry verified the gene expression patterns of key molecules, as shown by global gene arrays. Conclusions/interpretation Short-term exposure to hyperglycaemia can cause deleterious and persistent changes in arterial gene expression in vivo. Brief hypoglycaemia also adversely affects gene expression, although less substantially. Together, these results suggest that early correction of hyperglycaemia and avoidance of hypoglycaemia may both be necessary to avoid excess CVD risk in diabetes.

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Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat thoracic aorta

Cited by 76 publications

References 30 publications

Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta

Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta

Angiotensin II Type 1 Receptor Blocker Reduces Monocyte Adhesion to Endothelial Cells in Spontaneously Hypertensive Rats

Short-term hyperglycaemia causes non-reversible changes in arterial gene expression in a fully ‘switchable’ in vivo mouse model of diabetes

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