OBJECTIVETo investigate the effect of chronic enhanced external counterpulastion (EECP) on gene expression profiles of arterial endothelial cells (ECs) of pigs fed with high-cholesterol diet.

METHODSEight male pigs were fed with high-cholesterol diet for 12 weeks to induce arteriosclerosis and subjected to EECP for accumulative 36 h (2 h every other day for 18 sessions). Another 8 pigs on cholesterol-enriched diet and 6 normally fed pigs served as the arteriosclerosis model group and normal control group, respectively, and the high-cholesterol diet was maintained until the end of EECP treatment. The coronary artery was then isolated for transmission electro microscopy, and the abdominal aorta was observed using Sudan III staining. The gene expression profiles in ECs from the thoracic aorta using cDNA microarrays.

RESULTSMacrophages and foam cells were detected beneath the ECs in the coronary artery of pigs in the model group, but not in the other two groups. The ratios of Sudan III-positive area in the celiac aorta were significantly lower in normal control and EECP groups than in the model control group (P<0.05). Compared with the normal control group, the gene expressions of integrins-beta1 and CTGF were up-regulated in the model group. Compared with the model group, the expressions of integrins-beta1, CTGF and VCAM-1 were down-regulated and eNOS up-regulated in EECP group.

CONCLUSIONChronic EECP may reduce endothelial injury, down-regulate the gene expression level of integrin-beta1, CTGF and VCAM-1, lower cholesterol uptake and attenuate arterial endothelial inflammation to protect the pigs fed with high-cholesterol diet from arteriosclerosis.

Animals ; Aorta, Abdominal ; metabolism ; pathology ; Arteriosclerosis ; etiology ; genetics ; pathology ; Coronary Vessels ; metabolism ; pathology ; Counterpulsation ; methods ; Diet, Atherogenic ; Endothelial Cells ; metabolism ; Gene Expression Profiling ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Swine

We evaluated the risk of coronary-artery disease in patients with chronic renal failure (CRF) by measuring the coronary-artery calcium scores with electron beam CT (EBCT). A total of 81 CRF patients were divided into three groups; pre-dialysis (group I, n=35), hemodialysis (group II, n=31) and peritoneal dialysis (group III, n=15). The several serum biochemical markers and calcium score levels by EBCT were determined. The Ca x P products were significantly higher in groups II (p<0.05) and III (p<0.01) than in group I. The serum calcium levels were significantly higher in group III than in both group I (p<0.01) and II (p<0.05). The serum calcium level in 15 patients with a calcium score > 400 was significantly higher than the 66 patients with a score < or =400 (p<0.01). The calcium score was significantly higher in the 15 patients with cardiovascular complications than in the 66 patients without cardiovascular complications (628.9+/-904.8 vs. 150.4+/-350.9, p<0.01). EBCT seemed to be a good diagnostic tool for evaluating the risk of coronary-artery disease ''noninvasively'' in CRF patients who are at increased risk of cardiovascular morbidity and mortality.
Adolescent ; Adult ; Aged ; Calcinosis/etiology/metabolism/*radiography ; Calcium/blood/*metabolism ; Coronary Arteriosclerosis/etiology/metabolism/radiography ; Coronary Vessels/*metabolism ; Female ; Humans ; Kidney Failure, Chronic/complications/metabolism/*radiography/therapy ; Male ; Middle Aged ; Peritoneal Dialysis ; Renal Dialysis ; Research Support, Non-U.S. Gov't ; Risk Factors ; Tomography, X-Ray Computed

The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is one of the major causes of cardiac allograft failure. We investigated the early time-course of expresssion patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class I histocompatibility antigen. The allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha , INF-gamma) were examined in these specimens. The expressions of TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB (p65) expression was present on the cytoplasm and perinuclear area in the endothelial cells of coronary arteries on day 1. The peak of translocation of NF-B from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-kappaB expression gradually increased from day 1 until day 5, but a remarkable decrease was detected on day 7. Our data suggest that the increased expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of the expressions might be mandatory to avoid a potential graft failure.
Animal ; Chronic Disease ; Coronary Arteriosclerosis/etiology/*metabolism ; Cytokines/*biosynthesis ; *Graft Rejection ; *Heart Transplantation ; Histocompatibility Antigens Class I/analysis ; Intercellular Adhesion Molecule-1/biosynthesis ; Interferon Type II/biosynthesis ; Mice ; NF-kappa B/*biosynthesis ; Transplantation, Homologous ; Tumor Necrosis Factor/biosynthesis ; Vascular Cell Adhesion Molecule-1/biosynthesis