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

Vascular calcification is an active, invertible and highly regulated pathophysiological process, characterized by the deposition of hydroxyapatite crystal in vascular wall. Vascular calcification is classified into two types based on the sites of calcification: intimal atherosclerotic calcification and Mönckeberg's medial calcification. Medial vascular calcification is a pathological phenomenon commonly existed in diabetes, chronic kidney failure and aging. The current review summarizes the mechanisms of medial vascular calcification.
Calcinosis ; Humans ; Tunica Intima ; Vascular Calcification

AIM AND METHODSTo determine the relationship between the nuclear envelope nucleoside triphosphatase (EC 3. 6. 1. 15, NTPase) activity and the phenotypic modulation of vascular smooth muscle cell (VSMC), the NTPase activity was detected during restenosis after de-endothelialization in vascular wall. The activities of three enzymes involved in carbohydrate and nucleic acid metabolism were also investigated by spectrophotometry.

RESULTSThe activity of NTPase increased continuously and associated with the process of intimal thickening. Western blotting showed that expression of SMalpha-actin, as the marker of contractile phenotype of VSMC, decreased continuously. Osteopontin (OPN), the marker of synthetic phenotype of VSMC, was up-regulated during the process. These suggested that intimal injury induced phenotypic modulation of VSMC. The activities of 5'-nucleotidase, adenosine deaminase and succinate dehydrogenase increased and reached their peaks on 7 days after de-endothelialization. The changes of three enzymes were associated with proliferation in VSMC.

CONCLUSIONThe efflux of mRNA and the changes of enzyme activity involved in carbohydrate or nucleic acid metabolism may be the biochemical basis in the development and progression of restenosis.

Animals ; Constriction, Pathologic ; Endothelium, Vascular ; pathology ; Female ; Hyperplasia ; enzymology ; pathology ; Male ; Muscle, Smooth, Vascular ; pathology ; Nucleoside-Triphosphatase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tunica Intima ; enzymology ; pathology

AIMTo investigate the relationship between androgen level and the indexes indicating endothelial function in male patients with coronary heart disease (CHD).

METHODSWe registered the following data for 106 50-70-year-old men: age, weight, blood lipid, including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride, whether a smoker, sugar levels, blood pressure, free testosterone (FT), vascular cell adhesion molecule-1 (VCAM-1) and the intima-media thickness (IMT) of common carotid artery, common carotid diameter, maximum velocity in systolic phase, minimum velocity in diastolic phase and resistant index. Among the 106 men, 51 were patients with CHD. The relationships between FT level, VCAM-1 concentration and IMT were examined, respectively, using a stepwise linear regression technique among all the 106 men.

RESULTSThere was no statistical difference in terms of age, blood pressure, whether a smoker, sugar levels, HDL-C, minimum velocity in diastolic phase, resistant index between male CHD patients and controls; whereas results for weight, total cholesterol, low density lipoprotein cholesterol, triglyceride, VCAM-1 and IMT of male CHD patients were higher than those of controls; FT level and maximum velocity in systolic phase were lower. It was found that among all the objects, FT level was inversely correlated with IMT and VCAM-1 concentration.

CONCLUSIONFT level was inversely correlated with VCAM-1 concentration and IMT which are indicators of endothelial function.

Aged ; Carotid Artery, Common ; diagnostic imaging ; Coronary Disease ; blood ; physiopathology ; Endothelium, Vascular ; physiopathology ; Humans ; Male ; Middle Aged ; Testosterone ; blood ; Tunica Intima ; diagnostic imaging ; Tunica Media ; diagnostic imaging ; Ultrasonography ; Vascular Cell Adhesion Molecule-1 ; blood

Retinoic acids may inhibit vascular smooth muscle cell proliferation, but may promote endothelial cell proliferation in cell culture. However, little data are available about the effects of all-trans-retinoic acid (ATRA) on endothelial regeneration and functional recovery in an experimental model of vascular injury. Accordingly, we investigated whether ATRA may attenuate neointima formation and accelerate endothelial regeneration with functional recovery in balloon-injured rat aorta. Twelve-week-old male Sprague-Dawley rats underwent endothelial denudation of the thoracic aorta by balloon injury. Fourteen rats were fed a standard rat pellet diet. Another 14 rats were fed ATRA (1.5 mg/day) for 2 weeks. The animals were killed on day 14 for organ chamber study and morphometric analysis. Rats in the ATRA group had a significantly improved acetylcholine-induced relaxation response than those in control group. However, endothelial independent response was not significantly different between the two groups. The extent of reendothelialization was markedly superior in the ATRA group compared with control group (p>0.05). Furthermore, neointima area and the ratio of neointima to medial area were significantly less in ATRA group than in control group (p>0.05). In conclusion, ATRA may accelerate endothelial regeneration with functional recovery, and attenuate neointima formation in balloon-injured rat aorta.
Acetylcholine/pharmacology ; Animal ; Aorta, Thoracic/physiology ; Aorta, Thoracic/injuries ; Aorta, Thoracic/drug effects* ; Balloon Dilatation/adverse effects ; Endothelium, Vascular/physiology ; Endothelium, Vascular/drug effects ; Male ; Muscle Relaxation/physiology ; Muscle Relaxation/drug effects ; Muscle, Smooth, Vascular/physiology ; Muscle, Smooth, Vascular/drug effects ; Rats ; Rats, Sprague-Dawley ; Regeneration/physiology ; Regeneration/drug effects ; Tretinoin/pharmacology* ; Tunica Intima/physiology ; Tunica Intima/pathology* ; Tunica Intima/drug effects* ; Vasodilator Agents/pharmacology

BACKGROUNDThe dysfunction of vascular endothelial cells plays a key role in starting and facilitating restenosis. The acceleration of intima repair and the recovery of endothelial function would reduce the restenosis rate. This study was undertaken to assess the effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on the repair of damaged iliac arteries.

METHODSTwenty-four male New Zealand white rabbits undergoing primary iliac artery deendothelization were randomly divided into two groups (GM-CSF group and control group). The GM-CSF group received a subcutaneous injection of GM-CSF [10 microg x kg(-1) x d(-1)], and the control group was given a subcutaneous injection of equivalent saline. The iliac arteries of all animals were damaged by balloon after 7 days. The levels of nitric oxide (NO) were detected before, 1 week, 2 weeks and 4 weeks after angioplasty. The repair and hyperplasia of the intima were observed microscopically and the indices of stenosis were evaluated by computerized planimetry after 4 weeks of angioplasty.

RESULTSThe NO levels of the GM-CSF group were higher than those of the control group 2 weeks and 4 weeks after angioplasty [(91.92 +/- 11.57) micromol/L vs. (81.67 +/- 12.18) micromol/L; (97.67 +/- 10.13) micromol/L vs. (83.16 +/- 12.64) micromol/L]. Four weeks after balloon damage, histological examination showed that neointima formation, vascular smooth muscle cells and fibrous tissue of the GM-CSF group were less than those of the control group. The endothelium of the GM-CSF group was more integrated, and stenosis of lumen was slighter than that of the control group. Morphometry showed the lumen area of the GM-CSF group was larger than that of the control group [(1.27 +/- 0.31) mm(2) vs. (0.92 +/- 0.24) mm(2)], the neointimal area and percent of intima hyperplasia were significantly smaller than those of the control group [(0.85 +/- 0.34) mm(2) vs. (1.18 +/- 0.38) mm(2); (40 +/- 7)% vs. (55 +/- 6)%].

CONCLUSIONGM-CSF could facilitate the repair of the intima, reduce neointima formation, better the function of the endothelium, and decrease the rate of restenosis.

Angioplasty, Balloon ; adverse effects ; Animals ; Endothelium, Vascular ; pathology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Hyperplasia ; Iliac Artery ; Male ; Nitric Oxide ; blood ; Rabbits ; Tunica Intima ; drug effects ; pathology

BACKGROUND/AIMS: Behcet's disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis. We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography. METHODS: We studied 40 patients (24 males, mean age: 39.1+/-8.5 years) who were diagnosed by the international diagnostic criteria of Behcet's disease and 20 healthy controls (13 males, mean age: 40.2+/-5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed. RESULTS: The carotid IMT in the BD group was significantly higher than that in the control group (0.71+/-0.22 mm vs. 0.59+/-0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85+/-0.21 mm vs. 0.64+/-0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement. CONCLUSIONS: Despite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.
Adult ; Behcet Syndrome/complications/diagnosis/*pathology ; Carotid Arteries/*pathology/ultrasonography ; Case-Control Studies ; Endothelium, Vascular/pathology ; Female ; Humans ; Male ; Prognosis ; Prospective Studies ; Risk Factors ; Tunica Intima/*pathology/ultrasonography ; Tunica Media/*pathology/ultrasonography ; Ultrasonography, Doppler ; Vasculitis/pathology

OBJECTIVETo observe the effects of Tongguan Capsule on the mobilization and differentiation of bone marrow mononuclear cells (BMMNCs) to the injured carotid arteries.

METHODSThe rat model of injured carotid arteries was established. Mononuclear cells were separated from the bone marrow of donor rats, which were labeled by PKH 26 and then injected through the tail vein to the recipient rats with injured carotid arteries. The rats were randomly divided into two groups. Tongguan Capsule suspension was administered by gastrogavage to rats in the experiment group, while equal volume of normal saline was given to rats in the control group. Four weeks later the injured carotid arteries were harvested and frozen sections were made to observe the differences of intima area/media area ratio (Ai/Am). The difference of BMMNCs migrating to the injured carotid arteries between the two groups was observed under fluorescence microscope. The difference of the vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1) levels in serum were detected by ELISA.

RESULTSThe PKH 26 labeled cells appeared in the experiment group, while only little scattered fluorescent light points was presented in the control group. The intima area and the ratio of Ai/Am of the experiment group decreased more obviously than that of the control group (P<0.01). Two and 4 weeks later the VEGF and SDF-1 levels in serum of the experiment group were more obviously enhanced than those of the control group (P<0.01).

CONCLUSIONTongguan Capsule could promote the BMMNCs transplanting towards the intima of injured carotid arteries, and take part in the repair of the intima of injured carotid arteries.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Chemokine CXCL12 ; blood ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; Monocytes ; cytology ; drug effects ; Rats ; Rats, Wistar ; Tunica Intima ; cytology ; drug effects ; pathology ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo observe the effects of co-transfection of platelet derived growth factor antisense oligodeoxynucleotides (PDGF-AODN) and tissue-type plasminogen activator (tPA) gene on inhibition of intimal proliferation of auto-transplantion artery.

METHODSOne hundred male New Zealand rabbits were randomly divided into four groups (25 in each): Group A (control group), Group B (PDGF-AODN transfection group), Group C (tPA gene transfection group) and Group D (PDGF-AODN and tPA co-transfection group). The left and right external iliac arteries were transplanted reciprocally. The transplanted arteries were respectively soaked in PDGF-AODN, pBudCE4.1/tPA and PDGF-AODN plus pBudCE4.1/tPA solution about 15 minute before transplantation. The rabbits were sacrificed at 3d, 1w, 2w, 4w and 8w after operation. The specimens were harvested for pathologic examination, electron microscopy, chromogenic substrate test, 3H-TdR incorporation test and immunohistochemical staining.

RESULTThe scan electron microscopy showed that there were a few thrombocytes on vas-wall of Group C and D without thrombus, whereas there were abundant thrombocytes and thrombus forming on vas-wall of Group A and B. The intimal area, stenosis ratio of transplanted artery, 3H-TdR incorporation,the number of PDGF positive cell in Group D were significantly less than those in Group A (P<0.01),Group B and Group C (both P<0.05). The activity of tPA gene products in transplanted vas-wall of Group D was significantly higher than that of Group A (P<0.01).

CONCLUSIONLocal co-transfection of PDGF-AODN and tPA gene can effectively inhibit the proliferation of vascular smooth muscle cells, hyperplasia of intima and restenosis of transplanted artery.

Animals ; Endothelium, Vascular ; pathology ; Graft Occlusion, Vascular ; prevention & control ; Hyperplasia ; prevention & control ; Iliac Artery ; transplantation ; Male ; Oligodeoxyribonucleotides, Antisense ; biosynthesis ; genetics ; Platelet-Derived Growth Factor ; biosynthesis ; genetics ; Rabbits ; Random Allocation ; Tissue Plasminogen Activator ; biosynthesis ; genetics ; Transfection ; Tunica Intima ; 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