Late Lumen Loss After Coronary Angioplasty Is Associated With the Activation Status of Circulating Phagocytes Before Treatment

Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment. Methods and Results To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1ß, tumor necrosis factor-, IL-6, fibrinogen, C-reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1ß by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=.65; P<.0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1ß by stimulated monocytes. Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required

A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 ± 0.08 mm(2) (CCA), 0.14 ± 0.03 mm(2) (CIA) and 0.12 ± 0.04 mm(2) (AA) at 16 weeks (NS). The LD decreased with 0.49 ± 0.07 mm (CCA), compared to 0.22 ± 0.07 mm (CIA) and 0.07 ± 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 ± 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI

P38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level

The cytokine tumor necrosis factor (TNF) alpha was found to stimulate the p38 mitogen activated protein (MAP) kinase signalling cascade in human umbilical vein endothelial cells. TNFalpha increased the activity of the p38 substrate MAP kinase-activated-protein (MAPKAP) kinase 2 and the subsequent phosphorylation of the small heat shock protein Hsp27 about two to three fold. This stimulation was blocked almost completely by the specific p38 MAP kinase inhibitor SB203580. This inhibitor also suppressed the TNFalpha-induced surface expression of the endothelial adhesion molecule vascular cell adhesion molecule (VCAM)-1. In contrast, inhibition of p38 MAP kinase had no effect on the stimulated surface expression of the intercellular cell adhesion molecule (ICAM)-1. VCAM-1 mRNA accumulation induced by TNFalpha was not affected by SB203580, suggesting that the p38 MAP kinase signalling cascade regulates the endothelial expression of VCAM-1 at the post-transcriptional level

Angiotensin administration stimulates renal 11β-hydroxysteroid dehydrogenase activity in healthy men

Angiotensin administration stimulates renal 11β-hydroxysteroid dehydrogenase activity in healthy men.BackgroundWe examined whether acute administration of angiotensin modulates the activity of 11β-hydroxysteroid dehydrogenase (11βHSD), the intracellular enzyme catalyzing the interconversion between the hormonally active cortisol and inactive cortisone.MethodsTwenty-one male healthy subjects were examined after 1week of a low- and high-salt diet (50 and 200mmol/day, respectively). Separate infusions of angiotensin I (Ang I) and II (Ang II) were administered, both at rates of 4 and 8ng/kg/min. The ratios of tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone (THF + allo-THF/THE) and of free cortisol/free cortisone (UFF/UFE) in urine were measured as indices of overall 11βHSD set point and activity of renal 11βHSD type 2, respectively. Glomerular filtration rate (GFR) was measured by constant infusion of 125I-iothalamate.ResultsAng I and Ang II infusion dose-dependently increased mean arterial blood pressure (MAP) and plasma aldosterone, and decreased plasma renin activity (PRA) and GFR at both diets. Ang I and Ang II infusion resulted in a dose-dependent decrease in the excretion of UFF, UFE, and of the UFF/UFE ratio at both diets, without changing the urinary (THF + allo-THF)/THE ratio. Salt restriction did not affect these 11βHSD variables, but was accompanied by a decrease in UFF and UFE excretion.ConclusionThis study suggests that acute angiotensin administration stimulates the activity of 11βHSD type 2 in human kidney. Angiotensin might therefore exert a dual effect on the mineralocorticoid receptor (i.e., an indirect agonistic effect by increasing aldosterone availability and a direct or indirect antagonistic effect by stimulation of renal 11βHSD type 2 activity)