Establishment of a rat model with diet-induced coronary atherosclerosis

Coronary atherosclerotic disease is a serious disease in humans,but no suitable animal model is available currently for further studies.We used apolipoprotein E gene knockout（ApoE KO） rats to induce hypercholesterolemia through a special high cholesterol/bile salt diet（Paigen diet）,then analyzed aortic and coronaiy atherosclerosis lesions and the myocardial injury in order to establish a novel small animal model of coronary atherosclerosis.Plasma cholesterol of ApoE KO rats increased 7.6-fold compared with wild-type rats after 8 weeks on the Paigen diet.After 10 to 12 weeks of subsisting on the Paigen diet,ApoE KO rats developed mild aortic atherosclerosis with severe coronary atherosclerosis.Hematoxilyn and eosin staining showed that 11 out of 12 ApoE KO male rats had right coronary artery atherosclerosis,7 of them were〉70%occluded.Oil Red O（Lipid Stain）,Mac2 immuno-staining and Masson＇s tnchrome staining demonstrated substantial amounts of lipid,macrophages and collagen fibers in coronary atherosclerosis plaques.In addition,ApoE KO male rats had severe myocardial focal lesions with cholesterol ester as the main component in the lesions.In conclusion,ApoE KO rats developed severe hypercholesterolemia,coronary atherosclerosis and myocardial cholesterol ester deposition after subsisting on the Paigen diet and can be used as a novel animal model for studies on cholesterol metabolism and coronary atherosclerotic disease.

Insights Into Evaluating the Total Coronary Atherosclerosis Burden

The coronary plaque burden represents an essential tool for evaluating coronary blood flow and cardiovascular outcomes.However,the concept of“coronary plaque burden”does not accurately reflect the complex pathological progression of coronary artery disease.In this review,various aspects of the total coronary atherosclerosis burden are present,including its mechanics,geometrical characteristics,plaque morphology,coronary artery calcium deposition,and coronary inflammation,to provide a complete view.Different tools used to evaluate the coronary atherosclerosis burden are also assessed according to the most recent studies.Compelling evidence is provided by our findings to advocate for a comprehensive use of the term“coronary atherosclerosis burden”.

Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6

Background The relationship between inflammatory markers and the characteristics of coronary atherosclerosis plaques is uncertain. The aim of the present study was to evaluate the relationship between the characteristics of coronary atherosclerosis plaques and inflammatory markers such as high sensitivity C-reactive proteins （Hs-CRP） and interleukin-6 （IL-6）. Methods All patients suspected of having coronary heart disease （CHD） underwent Siemens 64-slice CT angiography （64-SCTA） to distinguish the quality of plaque of coronary artery lesions. Blood samples were taken to measure levels of serum Hs-CRP and IL-6 in different plaque groups and the control group and compared with the value of 64-SCTA for detection of coronary artery plaque. Results The sensitivity of detecting coronary artery plaque by 64-SCTA was 87.4%, the specificity was 87.1%, the positive predictive value was 82.2%, and the negative predictive value was 91.0%. Comparing the levels of serum Hs-CRP and IL-6 among plaque groups, the mean levels of serum Hs-CRP and IL-6 in three plaque groups were significantly higher than those in the control group （P 〈0.01）. The mean levels of serum Hs-CRP and IL-6 in the soft plaque group and mixed plaque group were significantly higher than those in hard plaque group （P〈0.01）. Plaque burden in the soft plaque group and mixed plaque group was significantly higher than in the hard plaque group （P 〈0.01）, but there was no statistical difference between the soft plaque group and mixed plaque group （P=-0.246）. There was a negative correlation between the CT scale and Hs-CRP and IL-6 levels in the soft plaque group （r= -0.621, P〈0.01, and r= -0.593, P 〈0.01 respectively）. There was a positive correlation between the plaque burden and Hs-CRP and IL-6 levels in the soft plaque group （r=0.579, P〈0.05 and r=0.429, P〈0.05 respectively）. Conclusions 64-SCTA is an effective way to distinguish the different quality of coronary atherosclerosis plaque. Serum Hs-CRP and IL-6 levels can be considered as the indexes to judge the degree of CHD and may reflect the activity of plaque in CHD patients. Thus it is important for clinical diagnosis and risk evaluation of acute coronary syndrome （ACS） patients.

Correlation among obstructive sleep apnea syndrome,coronary atherosclerosis and coronary heart disease

Epidemiologic investigations have shown that the morbidity of obstructive sleep apnea syndrome （OSAS） among adults is 2%-4%, among the population aged 30 years and over is 4.63%, and among patients with hypertension or coronary atherosclerostic disease （CAD） is as high as 30%-50%.1 Many studies have indicated that OSAS may be closely associated with the development of CAD since increased incidence and mortality of CAD were found in OSAS patients. However, although it has been confirmed that OSAS is an independent risk factor for hypertension, its exact correlation with CAD has not been entirely elucidated. The aim of the present study was to explore the correlation between the degrees of OSAS and CAD with the application of coronary artery angiography （CAA）, Gensini scoring evaluation system, and other risk factors which may contribute to CAD.

Relationship between high-sensitivity C-reactive protein level and angiographical characteristics of coronary atherosclerosis

A role for inflammation has become well established over the past decade or more in theories describing the atherosclerotic disease process. From a pathological viewpoint, all stages, ie, initiation, growth, and complication of the atherosclerotic plaque, might be considered to be an inflammatory response to injury. Several prospective studies recently showed that plasma high sensitivity C-reactive protein （hsCRP） levels, which are one of the markers of systemic inflammation, are a powerful predictor of future myocardial infarction and cardiac death among apparently healthy individuals. However, the association between the plasma hsCRP levels and the extent of coronary stenosis in subjects remains controversial. Some studies previously demonstrated such associations, whereas other could not found. Gensini＇s score assigns a severity score for a stenosed vessel depending on the degree of luminal narrowing and the importance of its location.

Relation of combined non-high density lipoprotein cholesterol and apolipoprotein B with Gensini Score of coronary atherosclerosis in non-diabetic acute coronary syndrome

Background Non-high-density lipoprotein cholesterol （non-HDL-C） and Apolipoprotein B （apoB） increase car- diovascular disease （CVD） risk, but few studies have explored the correlations of non-HDL-C and apoB with cor- onary atherosclerosis in non-diabetes acute coronary syndrome （ACS）. Methods The study enrolled 443 sub- jects with non-diabetic ACS, and all subject check coronary angiography, and coronary atherosclerosis were eval- uated using Gensini Score （GS） scale including small （GS 1-15）, middle （GS16-43）, and severe （GS≥44）. All sub- jects were classified into 4 groups： High apoB （≥90 mg/dL） and High non-HDL-C （≥130 mg/dL）, High non-HDL -C alone, High apoB alone, and normal apoB and non-HDL-C. Results After adjusted for risk factors, non-HDL -C and apoB were positively correlated with GS （ r = 0.075, P = 0.002 and r = 0.092, P 〈 0.001）. In the GS 0-15, high non-HDL-C ＋ high apoB group 29.3% and high apoB alone group 28.2% were significantly lower than nor- mal non-HDL-C＋ normal apoB group 48% （p = 0.010）. In the GS 16-43, high non-HDL-C alone group 50.4% and high apoB alone group 47.6% were significantly more than high non-HDL-C＋ high apoB group 34.1% （P = 0.036）. In the GS ≥44, high non-HDL-C＋ high apoB group 36.6% was significantly higher than high non-HDL- C alone group 16% and normal non-HDL-C＋ normal apoB 14.2%（P 〈 0.001）. Conclusions The high non-HDL- C and apoB are the risk factors for coronary artery atherosclerosis in non-diabetic ACS.

Advances in research of Apo C-Ⅲ and Coronary Atherosclerosis Heart Disease

Coronary atherosclerotic heart disease had been regarded as the leading killer of human being.The atherosclerotic lesion would cause blood flow blockage or lumen stenosis of coronary arteries,thus resulting in myocardial ischemic or sudden cardiac death.Though exact causes of coronary atherosclerosis heart disease is not known,the promising Apo C-Ⅲthat played a crucial role in metabolism of triglyceride-rich lipoproteins had been supposed to be one of the key factor of pathogenesis.In this review,we discuss roles of Apo C-Ⅲin the development of CAD and its insights being a new therapeutic target.

Research progress of magnetic resonance imaging on the correlation between coronary plaque properties and pericoronal fat

Because of the small size of coronary plaque and its continuous beating with the heart,the assessment of the nature of coronary atherosclerotic plaques by magnetic resonance imaging remains a challenge in current research.Recent studies have shown that changes in the pericoronary fat environment are closely related to the nature of coronary atherosclerotic plaques.At present,the new multi-modal magnetic resonance technology can quantitatively assess the changes of pericorral fat environment,which is expected to effectively evaluate the properties of coronary artery plaque.Therefore,it is of greater clinical importance to study pericoronary fat.Advances in the biological significance of pericoronary fat,comparative imaging for pericoronary fat assessment and clinical applications of its imaging will be reviewed.

Correlation between Serum Level of Adiponectin and Severity of Coronary Artery Atherosclerosis

Objectives To investigate the correlation between serum level of adiponectin and severity of coronary artery atherosclerosis. Methods Coronary angiographies were performed and serum levels of adiponectin were measured in 88 patients with suspected coronary heart disease （CHD）. Patients were divided into groups according to the coronary angiographies and Gensini＇s scores of coronary artery atherosclerosis. The serum levels of adiponectin were compared in different groups, and multiple regressions were used to analyze the correlation factors of adiponectin. Results （1）Serum adiponectin concentration in CHD group [ 7. 1 mg/L （2.4 - 21.1 mg/L） ] was decreased as compared with that in control group [ 11.6 mg/L （4.4 - 28.2 mg/L ）, P 〈 0. 01 ] ; （2）The serum levels of adiponectin fell while the Gensini＇ s scores of coronary artery atherosclerosis increased （P 〈 0. 05, P 〈 0. 01 ） ; （3）Serum level of adiponectin was positively correlated with the high-density lipoprotein cholesterol, while negatively correlated with the Gensini＇ s score of coronary artery atherosclerosis and triglyceride （P 〈 0. 01 ）. Conclusions Serum adiponectin concentration was decreased in patients with CHD. Low serum levels of adiponectin reflected the severity of coronary artery atherosclerosis. Adiponectin was a protective factor of cardiovascular system.

Expression characteristics of neutrophil and mononuclear-phagocyte related genes mRNA in the stable angina pectoris and acute myocardial infarction stages of coronary artery disease

Objective To investigate expression differences of neutrophil and mononuclear phagocyte related gene mRNAs among acute myocardial infarction （AMI）, stable angina （SA） and control groups, and then discuss their expression characteristics in the stable angina pectoris （SAP） and AMI stages of coronary artery disease （CAD）. Methods Whole Human Genome Oligo Microarrays were applied to assess the differential expression characteristics of neutrophil and mononuclear phagocyte related mRNAs in patients with AMI （n = 20）, SA （n = 20） and controls （n = 20）. Results （1） Almost all colony-stimulating factors （CSF） and their receptors related mRNAs was up-regulated in AMI and SA groups compared with the control group, and the expression of granulocyte-macrophage colony stimulating factor receptor （GM-CSFR） and granulocyte colony stimulating factor receptor （G-CSFR） mRNAs in the AMI group was significantly up-regulated compared with the other two groups （P 〈 0.01）. （2） The expression of mRNAs related to monocyte chemoattractant protein-1 （MCP-1）, CCR2 （MCP-1 receptor） and CXCR2 （IL-8 receptor） was significantly up-regulated （P 〈 0.01） in AMI group compared with SA and control groups IL-8 mRNA expression in the AMI group was clearly higher than the controls （P 〈 0.05）. （3） All mRNAs expression related to opsonic re- ceptors （IgG FoR and C3bR/C4bR） was significantly up-regulated in AMI group compared with SA and control group （P 〈 0.01）, and the SA group showed an upward trend compared with controls. （4） Most pattern recognition receptor （PRR）-related mRNAs expression was up-regulated in AMI group compared with SA and control groups. Most toll-like receptor （TLR） mRNAs expression was significantly up-regulated （P 〈 0.01） than the SA and control groups, macrophage scavenger receptor （MSR） mRNA was significantly up-regulated in AMI group compared with the control group （P 〈 0.01）, and the SA group showed an upward trend compared with the controls. Conclusions The expression of most neutrophil and mononuclear-macrophage function related genes mRNAs was significantly up-regulated by stages during the progression of CAD, suggesting that the adhesive, chemotactic and phagocytic functions of neutrophil and mononudear-macrophage were strengthened in the occurrence and development of coronary atherosclerosis and AMI. This also showed a stepped up- ward trend as the disease progressed.

Animal models of coronary heart disease

Cardiovascular disease,predominantly coronary heart disease and stroke,leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions.The dominant pathologic foundation for cardiovascular disease is atherosclerosis and,as to coronary heart disease,coronary atherosclerosis and resulting lumen stenosis,even total occlusions.In translational research,several animals,such as mice,rabbits and pigs,have been used as disease models of human atherosclerosis and related cardiovascular disorders.However,coronary lesions are either naturally rare or hard to be fast induced in these models,hence,coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions,thus unrepresentative of human coronary heart disease progression and pathology.In this review,we describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.

Congenital absence of the right coronary artery:A case report

BACKGROUND As a rare anomaly,congenital absence of the right coronary artery(RCA)occurs during the development of coronary artery.Patients with congenital absence of the RCA often show no clinical symptoms,and this disease is considered benign.The left coronary artery gives blood supply to the whole myocardium.The prevalence of congenital absence of the RCA is approximately 0.024%-0.066%.There are few cases reported as for this disease.In this work,a patient,with congenital absence of the RCA diagnosed by coronary angiography(CAG),was described.CASE SUMMARY A 41-year-old man arrived at our hospital for treatment,due to the repeated palpitations for a duration of one year.Considering the possibility of coronary heart disease,the patient underwent CAG that indicated the congenital absence of the RCA.Unfortunately,the patient refused to accept computed tomography coronary angiography(CTCA),to further confirm the congenital absence of the RCA.CONCLUSION Single coronary artery is a rare type of coronary artery abnormality,which usually has no obvious clinical manifestations and is considered as a benign disease.CAG is the main means by which congenital absence of the RCA can be diagnosed,and the disease can also be further confirmed by CTCA.

Cardiac evaluation of liver transplant candidates

Physicians previously thought that heart disease was rare in patients with end stage liver disease. However, recent evidence shows that the prevalence of ischemic heart disease and cardiomyopathy is increased in transplant candidates compared to most other surgical candidates. Investigators estimate that up to 26% of all liver transplant candidates have at least one critical coronary artery stenosis and that at least half of these patients will die perioperatively of cardiac complications. Cardiomyopathy also occurs in greater frequency. While all patients with advanced cardiac disease have defects in cardiac performance, a larger than expected number of patients have classical findings of dilated, restrictive and hypertropic cardiomyopathy. This may explain why up to 56% of patients suffer from hypoxemia due to pulmonary edema following transplant surgery. There is considerable controversy on how to screen transplant candidates for the presence of heart disease. Questions focus upon, which patients should be screened and what tests should be used. This review examines screening strategies for transplant candidates and details the prognostic value of common tests used to identify ischemic heart disease. We also review the physiological consequences of cardiomyopathy in transplant candidates and explore the specific syndrome of "cirrhotic cardiomyopathy".

Pathology of diabetic myocardiac microangiopathy

Objective To investigate the cause of high cardiovascular lethality in patients with diabetics mellitus. Methods Sections from autopsied coronary arteries and myocardium of dead patients with non-insulin-dependent diabetics mellitus and 12 dead control subjects were used for histomorphometric studies. Results The coronary atherosclerotic lesion in diabetics patients was not different in severity fi＇om those in controls. Nor was there difference in number ofmyofibers or diameters of myoeardic fibers and capillaries.But the capillary density and the ratio of capillary number to myocardic fiber number in diabetics group were significeantly reduced compared with control group（P〈0.0 l）,and the capillary basement membrane in the former was significantly thicker than in the latter（P〈0.01）.Conclision The decrease in number of capillaries and the thickening of basement membrane enhance myocardiac vulnerability to further ischemia and hypoxia,which may undelie high lethality of myocardiopathy in diabetic patients.

INTRAVASCULAR ULTRASOUND IMAGING OF ANGIOGRAPHICALLY "SILENT" LEFT MAIN CORONARY ARTERY ATHEROSCLEROSIS

Patients with left main coronary artery (LMCA) atherosclerosis have a poor prognosis compared with lesions in the other coronaries. Because of the methodological problems. LMCA atherosclerotic lesions are not frequently detected by coronary angiography. The purpose of the study was to reveal the existence of LMCA disease in patients with normal coronary arteries by using intravascular ultrasound imaging. Ninety-seven patients with angiographically normal coronary arteries were examined with a 3.5 F or 4.8 F. 20 MHz intravascular ultrasound catheter. The vessel, lumen and plaque areas were determined and percent area and diameter stenosis were calculated. Plaque formation with or without calcific deposits identified by ultrasound accoustic shadowing were regarded as signs of atherosclerosis.

Oxidized phospholipids and lipoprotein-associated phospholipase A_2 as important determinants of Lp(a) functionality and pathophysiological role

Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.

Pathology of atherosclerotic coronary artery disease in the young Indian population

Atherosclerotic coronary artery disease (CAD) is of great concern in young adults because of its potential to cause great incapacitation.This arena of cardiology has gained importance in South Asian countries,particularly India due to increased prevalence that is related to traditional risk factors,altered life styles and inherent risk factors.In this study,we sought to evaluate,at autopsy,the pathology of atherosclerotic CAD in young patients with ischemic heart disease (IHD).A 10-year retrospective autopsy-based study was carried out in a large tertiary-care centre and patients aged ≤45 years with IHD were selected.Out of 545 autopsied cases of IHD,95 patients (17.4%) were young.Among these 95 patients,84 (88.4%) had IHD related to atherosclerotic CAD;the youngest patient was 18years old.Predictably there was sole involvement of left anterior descending artery and the presence of fibrous plaques.Irrespective of the plaque morphology,the commonest complication was thrombosis produced by plaque erosion seen in 36.9% of patients.Acute coronary insufficiency was noted in 52 patients (61.9%),while healed infarctions were surprisingly noted in 28 patients (33.3%).Screening for IHD in the young population may help to improve prognosis by detecting subclinical disease,although more studies are necessary to establish reference limits for this young population.Additional research must also focus on treatment concerns that are specific to young patients.

Diagnosis of coronary artery disease using targeted post-mortem computed tomography coronary angiography:a case report

Targeted post-mortem computed tomography(PMCT)combined with coronary angiography has the potential to play a significant role in the investigation of sudden cardiac death.The authors utilized a targeted PMCT coronary angiography in a case involving a 53-year-old man who died from acute myocardial ischemia and cardiac decompensation which may result from coronary artery disease(CAD).The victim collapsed suddenly at work and died soon after arrival to hospital.The body was examined using PMCT and targeted PMCT coronary angiography.The left anterior descending coronary artery exhibited 75%-100%stenosis in the middle segment;however,the distal segment could not be clearly visualized.In addition,the left circumflex and right coronary artery exhibited calcification,atherosclerosis and an area of 50% stenosis.Signs of cardiogenic pulmonary oedema were also identified.The imaging results suggested that this individual had coronary atherosclerosis and probably died from CAD.The autopsy and histological examination revealed acute myocardial ischemia and myocardial scarring,confirming the cause of death while excluding other probabilities.In summary,targeted post-mortem computed tomography angiography(PMCTA)can visualize the arteries and estimate the degree of principal pathological changes.This method is a simple,reliable and sensitive technique for identifying the presence of coronary atherosclerosis.It is a valuable post-mortem forensic imaging method and should be recommended in the investigation of suspicious cardiac deaths.

Changes of junctions of endothelial cells in coronary sclerosis:A review

Atherosclerosis, the major cause of cardiovascular diseases, has been a leading contributor to morbidity and mortality in the United States and it has been on the rise globally. Endothelial cellecell junctions are critical for vascular integrity and maintenance of vascular function. Endothelial cell junctions dysfunction is the onset step of future coronary events and coronary artery dis-ease.

Clinical implications of increased expression of CD40L in patients with acute coronary syndromes

To investigate clinical implications of expression of CD40L in monocytes and changes in serum soluble CD40L in patients with acute coronary syndromes (ACS) Methods Sixteen control and 56 patients, including 24 with stable angina (SA), 20 with unstable angina (UA) and 12 with acute myocardial infarction (AMI) enrolled in this study Expression of CD40L in monocytes was analyzed by flow cytometry and sCD40L levels were measured by ELISA Results Expression of CD40L in monocytes and serum levels of sCD40L in UA and AMI patients were higher than in SA patients and controls In patients with AMI, sCD40L levels showed no significant increase when compared to patients with UA, while AMI patients had a peak level of sCD40L at 24 hours after AMI PTCA induced a marked rise in sCD40L levels in all patients, while CD40L expression in monocytes showed no difference between patients with PTCA, before and after Conclusion Enhanced level of serum sCD40L may be a reliable prognostic indicator for ACS and may represent a marker of coronary disease activity