Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.
Aged ; Calcinosis/metabolism ; Coronary Arteriosclerosis/pathology* ; Coronary Arteriosclerosis/metabolism* ; Coronary Vessels/pathology* ; Coronary Vessels/metabolism ; Coronary Vessels/chemistry* ; Female ; Human ; Immunohistochemistry ; Male ; Middle Age ; Sialoglycoproteins/biosynthesis ; Sialoglycoproteins/analysis*

BACKGROUNDLittle is known about the influence of metabolic syndrome (MetS) on coronary artery calcification (CAC) in China. In this article, we aimed to explore the distribution of CAC in populations with and without MetS, and estimate the influence of MetS and its components on CAC in a community-based population of Beijing.

METHODSA total of 1647 local residents of Beijing, age 40-77 years, were recruited for a cardiovascular risk factors survey and were determined fasting plasma glucose (FPG), blood lipids, and 64 multi-detector computed tomography (64-MDCT) coronary artery calcium score (CACS) measurement (Agatston scoring). The distribution of CAC was described, and the influence of MetS components on CAC was evaluated.

RESULTSIn this population, the prevalence and extent of CAC increased with increasing age and both were higher in MetS subjects compared to nonMetS subjects (all P < 0.05), with the exception of those older than 65 years old. The risk of CAC increased with increasing numbers of MetS components, and the odds ratios for predicting positive CAC in subjects with 1, 2, 3, and = 4 MetS components were 1.60, 1.84, 2.12, and 3.12, respectively (all P < 0.05). Elevated blood pressure, elevated FPG, elevated triglycerides, and overweight increased the risk of CAC, yielding odds ratios of 2.64, 1.67, 1.32, and 1.37, respectively (all P < 0.05).

CONCLUSIONSIn the Beijing community-based population, MetS increases the risk of CAC. The risk of CAC increases with increasing numbers of MetS components. Not only the number, but also the variety of risk factors for MetS is correlated with the risk of CAC. Elevated blood pressure, hyperglycemia, hypertriglyceridemia and overweight increase the risk of CAC.

Adult ; Aged ; China ; epidemiology ; Coronary Artery Disease ; epidemiology ; metabolism ; pathology ; Coronary Vessels ; metabolism ; pathology ; Female ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; metabolism ; pathology ; Middle Aged ; Risk Factors

OBJECTIVETo observe the developing changes of adventitia in restenosis after precutaneous transluminal angioplasty(PTA), and investigate the effect of androgen on restenosis through contrasting the castrated male rat models and its mechanism.

METHODSModels were constructed of castrated male rats and restenosis of the common carotid artery, and specimens were collected at the 3rd, 7th, 14th and 28th day respectively after modeling. Hematoxylin and eosin staining, immunohistochemical staining, and electronic microscopy were performed to observe the condition of restenosis.

RESULTSProliferating cells occurred in adventitia first and phenotype of adventitial cells was changed at the 3rd day after PTA. The adventitial proliferating index was the highest at the 7th day after PTA, and proliferating migration towards intimal was observed. The proliferating cells mostly occurred in the middle layer and neointima at the 14th day after PTA. The areas of adventitia and neointima were larger and the degrees of restenosis were higher in the castrated rats than in the non-castrated ones at different time points. Take the 14 d group, the adventitial area was[(3,566 +/- 337) micron2 vs (2,751 +/- 401) micron2, P = 0.008], the neointimal area[(3,553 +/- 477) micron2 vs (2,757 +/- 435) micron2, P = 0.025], the restenosis rate[(76 +/- 2)% vs (60 +/- 8)%, P = 0.005], and the proliferating index [(29 +/- 2)% vs (13 +/- 1)%, P < 0.001].

CONCLUSIONAdventitial proliferation and migration contribute to restenosis after PTA; Androgen in rats can physiologically relieve restenosis, probably through intervening in the activation of adventitia.

Actins ; analysis ; Androgens ; physiology ; Angioplasty, Balloon, Coronary ; Animals ; Bromodeoxyuridine ; metabolism ; Coronary Restenosis ; etiology ; pathology ; Coronary Vessels ; pathology ; ultrastructure ; Immunohistochemistry ; Male ; Orchiectomy ; Rats ; Rats, Sprague-Dawley

The external elastic lamina (EEL) serves as a barrier for cells and macromolecules between the media and adventitia in the vascular wall. We evaluated the morphological changes and quantitative assessments of the EEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Confocal microscopy analysis of the EEL from hypercholesterolemic coronary arteries revealed an altered pattern characterized by fragmentation and disorganization of the EEL associated with an increase in the thickness. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal coronary arteries, the EEL of hypercholesterolemic coronary arteries decreased in the percentage of their elastin content (30.80 +/- 1.64% vs. 47.85 +/- 1.82%, p = 0.001). The percentage of elastin content was negatively correlated with the vessel wall area (r = -0.82, p = 0.001). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima and adventitia. This study demonstrates that experimental hypercholesterolemia induced ultrastructural changes of the EEL in coronary circulation. The EEL may also be an atherosclerosis-prone area compared with the intima. The EEL may play an important role in the development of structural changes which characterizes the early phase of coronary atherosclerosis and vascular remodeling.
Animal ; Arteries/ultrastructure ; Arteries/enzymology ; Coronary Vessels/ultrastructure* ; Coronary Vessels/enzymology ; Elastic Tissue/ultrastructure* ; Elastic Tissue/enzymology ; Female ; Hypercholesterolemia/pathology* ; Hypercholesterolemia/enzymology ; Stromelysin 1/metabolism ; Swine

OBJECTIVETo investigate potential pathophysiological role of cardiac mast cells accumulation and degranulation on the collagen deposition after coronary microembolization (CME).

METHODSCME was induced in miniswine by selective infusion of 15X10(4) microspheres (diameter, 45 mum) into the left anterior descending artery groups (CME group, n=8). Some CME-induced animals were pretreated with the MC stabilizer tranilast (50 mg/kg, twice daily), beginning 2 weeks before CME and thereafter throughout the experimental period (CME +tranilast group, n=8), while some animals received tranilast without CME (tranilast group, n=8). Eight sham-operated animals without CME served as controls. After 30 days, the total number of MC and degranulating MCs and collagen deposition was assessed by histological and electronic microscopy studies.

RESULTSThe numbers of total and degranulating MCs and collagen volume fraction (CVF) at day 30 in CME group were significantly higher than those in controls (P <0.01). Treatment with tranilast significantly reduced the numbers of total and degranulating MCs and CVF at day 30 (all P <0.01). There was a significant positive correlation of the CVF with the number of total MCs (r=0.91, P <0.001) and degranulating MCs (r=0.92, P <0.001) over the CME myocardium.

CONCLUSIONMCs accumulation and degranulating contribute to myocardial fibrosis collagen deposition.

Animals ; Cell Degranulation ; Collagen ; metabolism ; Coronary Vessels ; pathology ; physiopathology ; Embolism ; pathology ; physiopathology ; Mast Cells ; pathology ; physiology ; Myocardium ; metabolism ; pathology ; Swine ; Swine, Miniature

The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5+/-8.3 yr), 12 late FAs (42.6+/-16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4+/-11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8+/-6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.
Adult ; Age Factors ; Coronary Artery Disease/*diagnosis/pathology/ultrasonography ; Coronary Vessels/*pathology/*ultrasonography ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Myelin Proteins/*metabolism ; Ultrasonography, Interventional

OBJECTIVETo study the expression of COX-2 and pregnancy associate plasma protein A (PAPP-A) in coronary arteries and their relationship with acute coronary syndrome.

METHODSTwenty-one autopsy cases with acute coronary syndrome encountered during the period from 2002 to 2007 were enrolled into the study. Another 21 autopsy cases without evidence of acute coronary syndrome were used as the controls. The right and left coronary arteries of each group were dissected, embedded and processed as paraffin sections. Immunohistochemical study for CD68 and alpha-actin was performed to highlight the presence of macrophages and smooth muscle cells, respectively. The expression of COX-2 and PAPP-A was evaluated.

RESULTSIn the acute coronary syndrome group, COX-2 was localized mainly in the cytoplasm of endothelial cells, macrophages and smooth muscle cells. COX-2 expression in the cytoplasm of smooth muscle cells (28.60%) was significantly higher than that in the control group (4.76%, chi(2) = 14.13, P< 0.05). There was a positive correlation on COX-2 and PAPP-A expression in smooth muscle cells of the media layer of coronary arteries in acute coronary syndrome group (r = 0.88, P < 0.05). The expression of PAPP-A in smooth muscle cells of the media layer in coronary arteries not associated with plaque formation, was higher than that when there were atherosclerotic plaques (chi(2) = 10.36, P < 0.05).

CONCLUSIONIn coronary arteries, COX-2 and PAPP-A play certain roles in the pathogenesis of acute coronary syndrome.

Acute Coronary Syndrome ; metabolism ; pathology ; Adult ; Aged ; Autopsy ; Coronary Vessels ; metabolism ; pathology ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Middle Aged ; Myocytes, Smooth Muscle ; metabolism ; Plaque, Atherosclerotic ; metabolism ; Pregnancy ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Young Adult

OBJECTIVETo investigate the pathology characteristic of femoral atherosclerosis through the comparision among femoral, carotid and coronary atherosclerosis.

METHODS15 elder autopsy cases were selected. Serial sections of femoral artery, carotid artery and coronary artery of all the cases were taken. Part of the tissue sections were selected for immunohistochemistry staining. Three markers against alpha-smooth muscle actin, CD68, and bax were performed respectively.

RESULTSOn the whole, both femoral and coronary atherosclerosis had a similar pathology characteristic in the lesion style and the distribution of smooth muscle cells and macrophages in the plaques. In comparing with the coronary atheroma, there were more smooth muscle cells and less macrophages in the femoral atherosclerotic plaques, expression of bax in macrophages stronger, and the expression of bax in smooth muscle cell was weaker. The pathology characteristic of femoral and carotid atherosclerosis was somewhat similar.

CONCLUSIONSThe pathology characteristic of atherosclerotic lesion in femoral artery was principally consistent with that of the coronary atherosclerosis except some differences presented in certain indexes.

Actins ; metabolism ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Atherosclerosis ; metabolism ; pathology ; Carotid Arteries ; metabolism ; pathology ; Coronary Artery Disease ; metabolism ; pathology ; Coronary Vessels ; metabolism ; pathology ; Female ; Femoral Artery ; metabolism ; pathology ; Humans ; Macrophages ; metabolism ; pathology ; Male ; Myocytes, Smooth Muscle ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo assess the effect of valsartan eluting-stents on restenosis and collagen deposition in neointima hyperplasia in rabbits.

METHODSValsartan eluting-stents and the carrier eluting-stents were made with patented multi-layers coating techniques. Bare stents (n = 8), carrier eluting-stents (n = 8) and valsartan eluting-stents (n = 10) were implanted into rabbit abdominal aortas, respectively. Quantitive angiography (QA) was performed before, immediately post and 3 months after stents implantations to determine the diameter of aortas. Rabbits were killed 3 months post stents implantation and the cross sections of the stented vessels were analyzed for neointimal formation: luminal area (LA), neointimal area (NIA), inner elastic lumina area (IELA), the maximal inner-membrane thickness (MIT) and percent stenosis. MASSON and picrosirius red staining were performed to observe the collagen deposition in neointima analyzed.

RESULTSThe mean aortic diameters measured by QA at different time points were similar between the groups. LA was significantly larger (5 016 269 microm(2) +/- 207,934 microm(2) vs. 4,345,548 microm(2) +/- 125,822 microm(2) and 4,302,061 microm(2) +/- 167,952 microm(2), P < 0.01 vs. valsartan stents) while NIA (441,577 microm(2) +/- 74,099 microm(2) vs. 1,119,635 microm(2) +/- 163,503 microm(2) and 1,135,636 microm(2) +/- 136,555 microm(2)) and MIT (116 microm +/- 12 microm vs. 240 microm +/- 30 microm and 192 microm +/- 21 microm) as well as percent stenosis (8% +/- 2% vs. 20% +/- 2% and 21% +/- 2%) were significantly reduced in valsartan eluting-stents group compared to bare and carrier stents groups. MASSON and picrosirius red staining revealed rich type III collagen deposition in neointima and spare type I collagen patched around stents struts in bare and carrier stents groups and collagen deposition was rarely seen in neointima and stents struts in valsartan eluting-stents group.

CONCLUSIONValsartan eluting-stents inhibited neointimal hyperplasia by decreasing collagen deposition.

Animals ; Collagen ; metabolism ; Coronary Restenosis ; metabolism ; pathology ; therapy ; Coronary Vessels ; pathology ; Drug-Eluting Stents ; Female ; Graft Occlusion, Vascular ; metabolism ; pathology ; Hyperplasia ; Male ; Rabbits ; Tetrazoles ; therapeutic use ; Tunica Intima ; pathology ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

To investigate the pathogenesis of accelerated graft atherosclerosis after rdiac transplantation, a genetically well-defined and reproducible animal del is required. We performed heterotopic intraabdominal heart transplantation tween the two inbred strains of mice. Forty hearts from B10.A mice were ansplanted into B10.BR mice. Recipients were sacrificed at 1, 3, 5, 7, 14, 28, d 42 days after implantation. The specimens from both donor and recipient were amined with fluorescent immunohistochemistry and the serial histopathologic anges were evaluated. In the donor hearts, ICAM-1 and VCAM-1 expressions were nimal at day 1 and they gradually increased, reaching their peaks on day 5 or and remained unchanged by day 42. However, there were very little expressions the recipients' hearts. Mean percent areas of intima in the donor coronaries vealed progressive increase by day 42. However, those in the recipients cupied consistently less than 5% of the lumen. In conclusion, we demonstrated at a heterotopic murine heart transplantation model was a useful tool to oduce transplantation coronary artery disease and that adhesion molecules on e cardiac allografts were activated very early and remained elevated at all me-points, nonetheless the arterial lesion was detected after day 28 and its ogression was accelerated thereafter.
Animal ; Coronary Vessels/pathology ; Heart Transplantation*/pathology ; Intercellular Adhesion Molecule-1/biosynthesis* ; Mice ; Myocardium/pathology ; Myocardium/metabolism* ; Time Factors ; Transplantation, Heterotopic*/pathology ; Vascular Cell Adhesion Molecule-1/biosynthesis*