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

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

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

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

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8+/-3.9 vs. 11.1 +/-1.9%, p<0.001) and increased IMT (0.51+/-0.10 vs. 0.42+/-0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1+/-2.5 vs. 9.9+/-3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.
Adult ; Diabetes Mellitus, Type 1/*complications ; Diabetic Angiopathies/*etiology ; Endothelium, Vascular/*physiology ; Female ; Humans ; Male ; *Microcirculation ; Tunica Intima/pathology ; Tunica Media/pathology ; Vasodilation

Increased intima-media thickness (IMT) and pulse wave velocity (PWV) are noninvasive markers of early arterial wall alteration and are more widely used in adult clinical research. We investigated whether IMT and PWV are useful predictors of cardiovascular risk in hypertensive adolescents. Fifteen hypertensive adolescents (13-18 yr old, systolic BP > or = 140 mmHg, diastolic BP > or = 90 mmHg) and seventeen normotensive subjects were included. Height, weight, obesity index, body mass index (BMI), and fat distribution were obtained from each group. Serum lipid, insulin, vitamine B12, folate, renin, aldosterone, angiotensin-converting enzyme (ACE), and homocysteine levels were compared. The carotid IMT and PWV were measured. Arterial wall compliance and distensibility were calculated with the equation. High systolic blood pressure significantly correlated with height, weight, BMI, obesity index, arm circumference, fat mass, and fat distribution. Hypertensive adolescents had significantly greater cIMT (carotid intima-media thickness) and lower elastic properties such as cross-sectional compliance and distensibility of the carotid artery. The carotid IMT significantly correlated with brachial-ankle PWV. In conclusion, the measurement of carotid IMT and brachial-ankle PWV might be useful to predict the development of atherosclerosis in hypertensive adolescents.
Adolescent ; Arteries/*pathology/physiopathology ; Body Mass Index ; Elasticity ; Female ; Humans ; Hypertension/*pathology/physiopathology ; Male ; Tunica Intima/*pathology/physiopathology ; Tunica Media/*pathology/physiopathology