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*

BACKGROUND AND OBJECTIVES: The recently discovered myokine irisin has a proposed role in adipose tissue metabolism. The aim of this study was to evaluate the relationship between serum irisin level and the coronary artery severity in patients with stable coronary artery disease (CAD). SUBJECTS AND METHODS: Sixty-three patients who underwent coronary angiography (CA) diagnosed with stable CAD and twenty-six patients with normal coronary artery (NCA) were enrolled in the study. Stable CAD patients were divided into two groups as high synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score (≥23) and lower SYNTAX score (<23). Serum irisin level measurement was carried out using human irisin colorimetric enzyme-linked immunosorbent assay (ELISA) commercial kit (AG-45A-0046EK-KI01, Adipogen, San Diego, CA, USA) as recommended by the manufacturer's protocol. RESULTS: The patients with stable CAD with a higher SYNTAX score (score ≥23) had significantly lower serum irisin levels (127.91±55.38 ng/mL), as compared the patients with a low SYNTAX score (score <23) (224.69±92.99 ng/mL) and control group (299.54±123.20 ng/mL). Irisin levels showed significant differences between all groups (p<0.001). CONCLUSION: Serum irisin level is an independent predictor of coronary artery severity in patients with stable CAD.
Adipose Tissue ; Angina, Stable* ; Atherosclerosis ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Vessels* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Metabolism ; Percutaneous Coronary Intervention ; Taxus ; Thoracic Surgery

The obstacles for cardiac imaging are motion artifacts due to cardiac motion, respiration, and blood flow, and low signal due to small tissue volume of heart. To overcome these obstacles, fast imaging technique with ECG gating is utilized. Cardiac exam using MRI comprises of morphology, ventricular function, myocardial perfusion, metabolism, and coronary artery morphology. During cardiac morphology evaluation, double and triple inversion recovery techniques are used to depict myocardial fluidity and soft tissue structure such as fat tissue, respectively. By checking the first-pass enhancement of myocardium using contrast-enhanced fast gradient echo technique, myocardial blood flow can be evaluated. In addition, delayed imaging in 10-15 minutes can inform myocardial destruction such as chronic myocardial infarction. Ventricular function including regional and global wall motion can be checked by fast gradient echo cine imaging in quantitative way. MRI is acknowledged to be practical for integrated cardiac evaluation technique except coronary angiography. Especially delay imaging is the greatest merit of MRI in myocardial viability evaluation.
Artifacts ; Coronary Angiography ; Coronary Vessels ; Electrocardiography ; Heart ; Magnetic Resonance Imaging* ; Metabolism ; Myocardial Infarction ; Myocardium ; Perfusion ; Respiration ; Ventricular Function

BACKGROUND: A preponderance of small low-density lipoproteins (LDL subclass phenotype B) has been closely associated with a high-risk for coronary artery disease. Lipoprotein lipase (LPL) gene polymorphisms have been found to be associated with coronary artery disease and lipid levels; but their impact on LDL particle size is less clearly established. METHODS: The LDL subclass phenotype was analyzed in 114 normal controls and 131 patients with coronary artery disease using the LipoPrint LDL system (Quantimetrix Co., Redondo Beach, CA, USA). HindIII and PvuII polymorphisms of LPL genes were analyzed using PCR-RFLP. Ser447 -Ter polymorphisms of LPL gene were analyzed using the PCR-based method and using mismatched primer and restriction digestion. The analysis of their associations with the LDL subclass phenotype and the LDL score was investigated. RESULTS: No statistical differences in the allelic frequencies of HindIII, PvuII and Ser447 -Ter poly-morphisms were observed between the control and patient groups. The G allelic frequency of Ser447 -Ter polymorphism was significantly higher in phenotype B than in the phenotype AandI group (P=0.043). HindIII, PvuII and Ser447 -Ter sites were in strong linkage disequilibrium. CONCLUSIONS: HindIII, PvuII and Ser447 -Ter polymorphisms were not directly linked with coronary artery disease. However, the Ser447 -Ter polymorphism is associated with the small LDL particle, which results in a change in lipid metabolism and might have an effect on the development of coronary artery disease.
Coronary Artery Disease* ; Coronary Vessels* ; Digestion ; Humans ; Linkage Disequilibrium ; Lipid Metabolism ; Lipoprotein Lipase* ; Lipoproteins* ; Lipoproteins, LDL ; Particle Size ; Phenotype

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

It has been reported that a change in the cellular redox state may be involved in the regulation of vascular tone, but the underlying mechanism is not fully understood. The present study was designed to investigate the cellular effect of sulfhydryl modifying agents in the coronary artery of rabbit using the tension measurement and whole cell clamping method. The application of diamide, a sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in a dose dependent manner. The fact that this diamide-induced relaxation was significantly attenuated by a pretreatment of 4-AP, and the coronary arteries precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4-AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries. Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was significantly enhanced by the membrane permeant oxidizing agents, diamide and DTDP, and were reversed by subsequent exposure to the reducing agent, DTT. Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had any effect on the activity of IdK, indicating that intracellular sulfhydryl modification is critical for modulating IdK activity. The Diamide failed to significantly alter the voltage dependence of the activation and inactivation parameters, and did not change the inactivation process, suggesting that diamide increases the number of functional channels without altering their gating properties. Since IdK has been believed to play an important role in regulating membrane potential and arterial tone, our results about the effect of sulfhydryl modifying agents on coronary arterial tone and IdK activity should help understand the pathophysiology of the diseases, where oxidative damage has been implicated.
Animal ; Arteries/physiology ; Arteries/drug effects ; Arteries/cytology ; Coronary Vessels/physiology ; Coronary Vessels/drug effects* ; Coronary Vessels/cytology ; Female ; Male ; Oxidants/pharmacology* ; Potassium Channels/physiology ; Rabbits ; Reducing Agents/pharmacology* ; Sulfhydryl Compounds/metabolism*

OBJECTIVETo investigate the dynamic changes of cardiomyocyte apoptosis and the role of death receptor apoptotic pathway in a rat model of coronary microembolization (CME).

METHODSAdult rats were randomized to coronary microembolization (CME group, n = 63) or sham-operated group (S group, n = 55). CME model was established by aortic injection of 0.1 ml microspheres (42 microm, 3 x 10(4)/ml) into the left ventricle when the ascending aorta was temporarily clamped.S group received 0.1 ml saline injection and survived rats were randomly examined at 0, 3, 6, 12 and 24 hour post CME (n = 10 each). Heart function was evaluated by echocardiography. Myocardium sample was stained with hematoxylin-eosin and hematoxylin-basic fuchsin-picric acid to detect infarct areas. Cardiomyocyte apoptosis was detected with TUNEL staining. The expression of caspase-3 and caspase-8 was measured by Western blot analysis.

RESULTSCompared with S group, the left ventricular ejection fraction was significantly decreased and left ventricular end-diastolic diameter was significantly increased in CME group (all P < 0.05) except 0 hour CME group. The infarct sizes were similar in 3 hour, 6 hour, 12 hour, and 24 hour CME groups (P > 0.05). The apoptosis index (AI) in CME group were significantly higher at each time point compared to S group (P < 0.05) except 0 hour CME group and peaked at 6 hours. Apoptotic cardiomyocytes were found mainly in the myocardial microinfarcted area and border zones. The relative expression of caspase-3 and caspase-8 in CME group were both significantly increased at 3 hours and peaked at 6 hour post CME (P < 0.05).

CONCLUSIONCardiomyocytes apoptosis was significantly increased after coronary microembolization via activating death receptor apoptotic pathway in this coronary microembolization model.

Animals ; Apoptosis ; Coronary Vessels ; pathology ; Male ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Death Domain ; metabolism ; Thromboembolism ; metabolism ; pathology

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

BACKGROUND: Metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, over- weight and abdominal fat distribution, dyslipidemia and hypertension, is associated with subsequent de- velopment of type 2 diabetes mellitus and cardiovascular disease, especially coronary heart disease. The aim of the study is to assess the relationship between metabolic syndrome and coronary heart disease in elderly greater than 65 years old. METHODS: Eighty two elderly patients greater than 65 years old who underwent coronary angiography were divided into two groups with metabolic syndrome or without metabolic syndrome, and assessed the association with coronary angiographic finding. The metabolic syndrome factors and cardiovascular risk factors of JNC 7 were investigated to assess the relationship with coronary heart disease in elderly. Coronary heart disease was defined as 50% or greater diameter in stenosis of coronary artery in coronary angiography. RESULTS: In elderly patients with metabolic syndrome, coronary angiographically abnormal findings(p<0.05) and multi vessel disease findings(p<0.05) were presented significantly higher than non metabolic syndrome patients. In elderly patients with 3 and more cardiovascular risk factors of JNC 7, coronary angiographically abnormal findings(p<0.05) and multi vessel disease findings(p=0.059) were presented more than the other patients. Diabetes mellitus was related significantly with coronary heart disease(p value 0.044). CONCLUSION: In elderly patients, metabolic syndrome was significantly related with coronary heart disease and diabetes mellitus had strong relationship with coronary heart disease. Metabolic syndrome and cardiovascular risk factors of JNC 7 should be further evaluated to assess the relationship with coronary heart disease in the future.
Abdominal Fat ; Aged* ; Cardiovascular Diseases ; Constriction, Pathologic ; Coronary Angiography ; Coronary Disease* ; Coronary Vessels ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dyslipidemias ; Glucose ; Heart ; Humans ; Hypertension ; Insulin ; Metabolism ; 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