Intimal accumulation of smooth muscle cells contributes to the development and progression of atherosclerotic lesions and restenosis following endovascular procedures. Arterial smooth muscle cells display heterogeneous phenotypes in both physiological and pathological conditions. In response to injury, dedifferentiated or synthetic smooth muscle cells proliferate and migrate from the tunica media into the intima. As a consequence, smooth muscle cells in vascular lesions show a prevalent dedifferentiated phenotype compared to the contractile appearance of normal media smooth muscle cells. The discovery of abundant stem antigen-expressing cells in vascular lesions also rarely detected in the tunica media of normal adult vessels stimulated a great scientific debate concerning the possibility that proliferating vascular wall-resident stem cells accumulate into the neointima and contribute to the progression of lesions. Although several experimental studies support this hypothesis, others researchers suggest a positive effect of stem cells on plaque stabilization. So, the real contribute of vascular wall-resident stem cells to pathological vascular remodelling needs further investigation. This review will examine the evidence and the contribution of vascular wall-resident stem cells to arterial pathobiology, in order to address future investigations as potential therapeutic target to prevent the progression of vascular diseases.
Adult ; Endovascular Procedures ; Humans ; Myocytes, Smooth Muscle ; Neointima ; Pathology* ; Phenotype ; Stem Cells* ; Tunica Media ; Vascular Diseases

Endothelial cells play a key role in pathological processes such as cancer cell metastasis, atherosclerosis, and diabetic retinopathy. Vascular smooth muscle cells directly involve in the formation of atheroma in atherosclerosis. Some kinds of the endothelial cells are simply harvested from the umbilical veins, the tunica intima of aortic walls, the retina using various enzymes solutions. Those purely isolated cells provide a powerful tool in vitro studies of the endothelial cell related diseases. In this context, the cultured smooth muscle cells after the isolation from the tunica media of aortic walls are also used for elucidating the pathogenesis of atherosclerosis. Here, I briefly introduce articles that include the isolation of human umbilical vein endothelial cells (HUVEC), aortic endothelial and smooth muscle cells, retinal microvascular endothelial cells (RMEC), as well as the diseases' applications of these cells.
Atherosclerosis ; Diabetic Retinopathy ; Endothelial Cells ; Human Umbilical Vein Endothelial Cells ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Neoplasm Metastasis ; Pathologic Processes ; Plaque, Atherosclerotic ; Retina ; Retinaldehyde ; Tunica Intima ; Tunica Media ; Umbilical Veins ; Vascular Diseases

BACKGROUNDVascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis, postangioplasty restenosis and transplant arteriopathy. Recently, pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis. But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not yet fully understood.

METHODSDouble-transgenic mice knockout of LDL receptor gene (LDL -/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL -/- mice with the GFP-expressing transgenic mice. LDL -/- mice (22 - 24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice. Four weeks later, a nonconstrictive cuff was placed around the right femoral artery. After another 2 weeks, both right and left femoral arteries were harvested and subjected to histochemical analysis. Apoptosis was analyzed in situ using TUNEL assay.

RESULTSTwo weeks after cuff placement, atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells. The tissue stained with anti-alpha smooth muscle actin (SMA) antibody, showed a number of SMA-positive cells in the intimal lesion area. They were also positive for GFP, indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions. Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP. The intima and media showed a large number of TUNEL-positive signals after 2 weeks cuff injury, indicating the presence of apoptosis in vascular remodeling.

CONCLUSIONSAtherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular injury under the hypercholesterolemic conditions. Our data also clearly indicate that bone marrow-derived cells differentiated to smooth muscles and endothelial cells in the formation of these lesions in the presence of hypercholesterolemia.

Animals ; Apoptosis ; Atherosclerosis ; pathology ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Movement ; Endothelial Cells ; pathology ; Female ; Hematopoietic Stem Cells ; pathology ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular ; pathology ; Receptors, LDL ; physiology ; Tunica Intima ; pathology ; Tunica Media ; pathology

Experimental subarachnoid hemorrhage(SAH) was produced in adult cats by injection of autologous blood(6ml) into prepontine cistern by tranclival approach and cisterna magna. The animals were sacrificed 1, 3, 5, 7 or 14 days later and basilar artery segments were prepared for electron microscopy. The following observations were made: 1) 1 to 7 days after SAH, electron micrograph showed round-shaped endothelial cells in tunica intima and disappearance of zonular occludens. Endothelial detachment from internal elastic membrane and intracytoplasmic vacuolation of endothelial cells as well as destruction of mitochondrial cirstae in tunica media. 2) 14 days after SAH, electron micrograph showed the normal findings in tunica intima and tunica media of the vessel walls. On the basis of the above findings, I found that the ultrastructural changes in the basilar arterial wall, which had presumably developed as a consequence of experimental SAH were reversible.
Adult ; Animals ; Basilar Artery* ; Cats ; Cisterna Magna ; Endothelial Cells ; Humans ; Membranes ; Microscopy, Electron ; Subarachnoid Hemorrhage* ; Tunica Intima ; Tunica Media

Experimental subarachnoid hemorrhage(SAH) was produced in adult cats by injection of autologous blood(6ml) into prepontine cistern by tranclival approach and cisterna magna. The animals were sacrificed 1, 3, 5, 7 or 14 days later and basilar artery segments were prepared for electron microscopy. The following observations were made: 1) 1 to 7 days after SAH, electron micrograph showed round-shaped endothelial cells in tunica intima and disappearance of zonular occludens. Endothelial detachment from internal elastic membrane and intracytoplasmic vacuolation of endothelial cells as well as destruction of mitochondrial cirstae in tunica media. 2) 14 days after SAH, electron micrograph showed the normal findings in tunica intima and tunica media of the vessel walls. On the basis of the above findings, I found that the ultrastructural changes in the basilar arterial wall, which had presumably developed as a consequence of experimental SAH were reversible.
Adult ; Animals ; Basilar Artery* ; Cats ; Cisterna Magna ; Endothelial Cells ; Humans ; Membranes ; Microscopy, Electron ; Subarachnoid Hemorrhage* ; Tunica Intima ; Tunica Media

This study is performed to reveal the changes of the arterial wall, especially, tunica intima and tunica media, after endothelial denudation and the effects of dexamethasone sodium on intimal hyperplasia morphologically in the rat. After arterial denudation by modified air drying technique, dexamethasone 1, 200 mg/kg/day was administered intramuscularly daily from the day of operation for 14 days. At 5 DAT (days after treatment) and 14 DAT, tunica intima was greatly thickened in control groups compared with normal group, but not in the dexamethasone-treated groups. Light microscopically, greatly increased cells and intercellular matrix in the tunica intima are observed in control group, but not in the dexamethasone-treated group. In the TEM observation, the cells considered as myofibroblasts and extracellular matrix were greatly increased in both tunica intima and tunica media just below the internal elastic lamina in the control group. Myofibroblasts and extracellular matrix migrated through the apertures of internal elastic lamina into the endothelial layer. Characteristic false internal elastic lamina also found. In dexamethasone-treated group, myofibroblasts and extracellular matrix decreased significantly, and apoptotic electron-dense cells, fragmented nucleus and autophagic vacuoles are observed. Through the apertures of internal elastic lamina, comma-shaped fragmented nuclei migrated into the tunica intima. These results suggest that dexamethasone inhibits the myofibroblast-transformation and proliferation of smooth muscle cells, migration of myofibroblasts and matrix synthetic activity, and induces the apoptosis of smooth muscle cells under the internal elastic lamina.
Animals ; Apoptosis ; Dexamethasone* ; Extracellular Matrix ; Hyperplasia* ; Myocytes, Smooth Muscle ; Myofibroblasts ; Rats ; Sodium ; Tunica Intima ; Tunica Media ; Vacuoles

We have examined 24 human aortas aged 46 ~ 90 years obtained from autopsies. Most exhibited gross lesions of some degree on the lumenal surface. Using hot alkaline treatment (0.1 N NaOH) at 70 ~ 75degreeC for 5 hours, we extracted and quantitated elastin portions from the aortic wall in 3 different segments (UTA = upper thoracic aorta, LTA = lower thoracic aorta, AA = abdominal aorta). We have found UTA had 70.6% +/- 1.39 (SE), LTA 61.6% +/- 1.94 (SE), AA 49.2% +/- 1.84 (SE) elastin respectively based on wet weight. The differences between segments are statistically significant (p < 0.05, 0.025). However, there is no significant correlation between the age of the patients and the relative amounts of elastin in each segment. We have also observed the structure of elastin in the internal elastic lamina (IEL) and tunica media (TM) with SEM (scanning electron microscopy), and discovered that the IEL shows various forms of elastolysis-broken sheets, discontinuity, various sizes of lumps, vesicles, and possible newly formed elastin in the aortic lesions (Song and Roach submitted to YMJ). From these studies we conclude that elastin in the aortic wall remains well balanced quantitatively with age in spite of evidence suggesting vigorous degeneration and regeneration in the atherosclerotic lesions.
Aging* ; Aorta* ; Aorta, Thoracic ; Atherosclerosis* ; Autopsy ; Elastin* ; Humans* ; Plaque, Atherosclerotic ; Regeneration ; Tunica Media

BACKGROUNDS/AIMS: It has been suggested that there is a differential response of the vasculature to systemic risk factors for atherosclerosis. We sought to evaluate the impact of hypertension on the carotid arterial wall using new methods that can measure each arterial wall layer. METHODS: The study subjects consisted of 163 patients who underwent carotid arterial scanning using high-resolution ultrasound that could measure the left carotid intima-media, intima, and media separately. The individual carotid arterial wall thickness was measured off-line by a new method using the Canny edge-detection algorithm. RESULTS: Hypertensive patients (n=79, mean age 61.8 years) had a higher prevalence of diabetes (31.6% vs 11.9%, p=0.004) and a lower level of HDL-cholesterol than did normotensive patients (41.8+/-11.0 mg/dL vs 45.7+/-10.0 mg/dL, p=0.019). Hypertensive patients had higher carotid intima-media thickness (CIMT, 0.81+/-0.21 mm vs 0.74+/-0.18 mm, p=0.003) and carotid medial thickness (CMT, 0.46+/-0.12 mm vs 0.42+/-0.09 mm, p=0.007) than did normotensive patients, whereas carotid intimal thickness (CIT) was not significantly different (0.34+/-0.04 mm vs 0.34+/-0.04 mm, p=0.196). Multivariate analysis revealed that the independent factors of CIMT were CMT (beta=0.915, p<0.001), hypertension (beta=0.076, p=0.008), age (beta=0.074, p=0.010), and sex (beta=-0.079, p=0.005). Pearson correlation coefficient between CIMT and CMT was higher (r=0.932, p<0.001 vs r=0.445, p<0.001) than that between CIMT and CIT. The correlation between CIMT and CMT was higher (r=0.940, p<0.001 vs r=0.910, p<0.001) in hypertensive patients than in normotensive patients, whereas that between CIMT and CIT was lower (r=0.344, p=0.002 vs r=0.583, p<0.001) in hypertensive patients. CONCLUSIONS: The increased CIMT is caused by increased CMT in hypertensive patients, and this finding is compatible with the medial hypertrophy seen in hypertension. The carotid medial layer should be the focus of attention in future studies looking at hypertensive patients.
Atherosclerosis ; Blood Proteins ; Carotid Arteries ; Carotid Intima-Media Thickness ; Humans ; Hypertension ; Hypertrophy ; Multivariate Analysis ; Prevalence ; Risk Factors ; Tunica Media

OBJECTIVETo understand whether hyperhomocysteinemia and early arterial atherosclerosis exist in simply obese children.

METHODSTotally 68 simply obese children (age 6-14 years, mean 10.8 +/- 2.3 years) were enrolled in this study, 50 were male and 18 were female. Body mass index (BMI) of the obese children was equal to or more than 22. The height of the children was (145 +/- 22) cm. Meanwhile, 26 normal children (age 6 - 14 years, mean 10.9 +/- 2.0 years) were selected as control group, 17 of these children were male and 9 were female. Their height was (148.5 +/- 5.8) cm. There were no significant differences in height and age between the obese and the control children. The carotid intimal-medial thickness (IMT), brachial artery flow-mediated vasodilation were examined by Doppler Flow/Dimension System and the liver was examined by B-mode ultrasound imager. Plasma homocysteine was determined by the automated chemiluminescent enzyme immunoassays. Serum lipid concentration was determined by biochemical analytic method. Blood pressure of the right upper limbs was measured. A detailed medical and family history was systematically recorded.

RESULTSBMI was (27.8 +/- 4.5) in the obese children and (16.2 +/- 2.5) in the controls. There was significant difference between two groups (P < 0.01). The obese children had significantly increased values than the controls for the carotid intimal-medial thickness (P < 0.01). Right carotid IMT, right inner-carotid IMT, left carotid IMT and left inner-carotid IMT were respectively (0.54 +/- 0.13) mm, (0.69 +/- 0.14) mm, (0.52 +/- 0.12) mm and (0.67 +/- 0.14) mm in obese children and were respectively (0.45 +/- 0.04) mm, (0.46 +/- 0.04) mm, (0.45 +/- 0.05) mm and (0.46 +/- 0.03) mm in control groups. Conversely, the flow-mediated brachial artery dilation of the obese children was significantly lower than that of the controls [(11.0 +/- 4.3)% vs. (17.5 +/- 4.9)%, P < 0.01]. The obese children had higher level of plasma homocysteine than the controls [(7.9 +/- 2.7) micromol/L vs. (5.6 +/- 2.1) micromol/L, P < 0.01]. Total cholesterol (TC) in the obese children dramatically increased, so did triglyceride concentration (TG), LDL-cholesterol (LDL-ch) and apolipoprotein-B (apo-B). Of the obese children, had fatty liver or the tendency to fatty liver. Six cases of the 68 obese children (8%) had hypertension. Of the 68 obese children, 57 (84%) had the history of consuming excessive food or taking less exercise. Forty-four percent of the obese children (30/68) came from the obese families in which at least one of the parents or grandparents was obese. Twenty-nine percent (20/68) and 22% (15/68) of the obese children respectively came from the families in which at least one of the parents or grandparents suffered from hypertension or coronary heart disease.

CONCLUSIONEarly arterial atherosclerotic changes existed in simply obese children. Hyperhomocysteinemia may be an important factor of the obesity-induced early arterial atherosclerosis during childhood.

Adolescent ; Atherosclerosis ; blood ; etiology ; Carotid Artery Diseases ; etiology ; Child ; Female ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; complications ; Lipids ; blood ; Male ; Obesity ; blood ; complications ; Tunica Intima ; pathology ; Tunica Media ; pathology

BACKGROUNDThis study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects.

METHODSMultiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling.

RESULTSIntima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD > ID > II, P < 0.05). Carotid internal diameter, distensibility and stiffness were similar among the DD, ID and II genotypes of ACE (P > 0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%, and 79.5% vs 40.5%, respectively, P < 0.001). In multiple stepwise regression analysis, independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes (P < 0.001), age (P < 0.001) and carotid internal diameter (P = 0.032). Moreover, triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype (P < 0.05).

CONCLUSIONSThe I/D polymorphism of the ACE gene was related to IMT, but not to internal diameter, distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.

Asian Continental Ancestry Group ; genetics ; Carotid Arteries ; pathology ; China ; Humans ; Hypertension ; pathology ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Tunica Intima ; pathology ; Tunica Media ; pathology