Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice.
(49/1622)
Expression of human lecithin cholesterol acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high cholesterol diets, expression of CETP in LCAT-Tg mice reduced total cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL cholesterol levels. CETP normalized both the plasma clearance of [(3)H]cholesteryl esters ([(3)H]CE) from HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and controls = 6.4 +/- 0.16) as well as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse cholesterol transport. (+info)
Unique vascular morphology of the fourth aortic arches: possible implications for pathogenesis of type-B aortic arch interruption and anomalous right subclavian artery.
(50/1622)
OBJECTIVE: Neural crest-derived cells were previously shown to participate in vessel wall formation of the great thoracic arteries, and their contribution was proposed to affect morphology and physiology of these vessels in the chick. The present investigation was undertaken to examine vascular differentiation and morphogenesis of the neural crest-derived aortic arches in mammals. METHODS: Using immunohistochemical markers for smooth muscle cell differentiation and a neurofilament marker, we examined morphogenesis of the great arteries in mice, ranging from embryonic day 11.5 to the adult. RESULTS: We observed that in the 4th aortic arch arteries early media formation differed from the other arteries, in that they almost completely lacked (or showed decreased) actin expression in certain areas. This discontinuity in actin expression persisted throughout much of foetal development, in the form of circular segments of cells displaying decreased staining for smooth muscle markers, both at the left and right side of the arterial tree. In adult mice, the 4th arch artery derivatives, segment B of the aortic arch and the proximal right subclavian artery, were observed to differ from adjoining vessels in their smooth muscle and elastic composition. Staining for neurofilaments revealed close association of the developing segments with apparent sensory afferent vascular innervation. CONCLUSION: The unique areas of the 4th arch artery identified here reflect the basic segmental patterning of the early embryonic pharyngeal arches. These segments correlate with sites that are predisposed to interruption or severe hypoplasia, and may thus reveal part of the aetiology of type-B aortic arch interruptions and arteria lusoria. (+info)
Aortic atherosclerotic debris detected by trans-oesophageal echocardiography--a risk factor for cholesterol embolization.
(51/1622)
The clinical syndrome of cholesterol embolization is uncommon but is associated with a poor prognosis. Patients with severe atheromatous disease of the aorta appear to be at particular risk from cholesterol embolization, particularly following vascular instrumentation or surgery. Trans-oesophageal echocardiography is the investigation of choice for imaging atherosclerotic disease of the aorta, and may be useful in assessing the risk of vascular procedures, and diagnostically helpful in patients with suspected cholesterol emboli syndrome. We report five cases of athero-embolism, and illustrate the role of trans-oesophageal echocardiography in making a diagnosis of cholesterol embolization. (+info)
Can knitting structure affect dilation of polyester bifurcated prostheses? A randomized study with the use of helical computed tomography scanning.
(52/1622)
PURPOSE: The aim of this study was to prospectively evaluate the postoperative dilation of two types of knitted polyester arterial prostheses with the use of helical computed tomographic scanning. METHODS: Thirty-four patients who underwent aortoiliac or aortofemoral bifurcation grafting were randomized to receive a collagen-sealed warp-knitted polyester graft (n = 16 patients) or a gelatin-sealed Koper-knitted polyester graft (n = 18 patients). Alterations in size of all parts of the grafts were evaluated by helical computed tomographic scanning at postoperative day 8, at 3 months, and at 6 months. RESULTS: On postoperative day 8, the mean dilation of the Koper-knitted grafts was 18% +/- 8% for the stem and 15% +/- 12% for the limbs. At the same time period, the mean dilation of warp-knitted grafts was 27% +/- 13% for the stem and 33% +/- 18% for the limbs. No increase in graft dilation was observed at 3 and 6 months. Despite the wide range of values among patients with the same graft type, at each time interval, the Koper-knitted grafts dilated significantly less than the warp-knitted grafts (P <. 05). CONCLUSION: In this randomized study, helical computed tomographic scanning was an accurate technique with which to assess graft dilation. For a 6-month follow-up interval, the Koper-knitted polyester structure dilated less than the warp-knitted structure. Longer-term serial scans should allow a better understanding of the clinical significance of graft dilation. (+info)
Aortoduodenal fistula after endovascular stent-graft of an abdominal aortic aneurysm.
(53/1622)
Despite satisfying short- and middle-term effectiveness and feasibility, endovascular stent-grafting for abdominal aortic aneurysm is still under evaluation. We report a case of an aortoduodenal fistula after the use of this technique. Enlargement of the upper aneurysmal neck was followed by caudal migration of the major portion of the stent-graft, which resulted in kinking of the device in the aneurysmal sac. Ulcerations were found on adjacent portions of both the aneurysmal sac and the adjacent duodenum. Only the textile portion of the prosthetic contralateral limb separated the aortic lumen from the corresponding duodenal lumen. Early detection of complications after stent-grafting is essential to allow successful treatment, either surgical or endoluminal. (+info)
Increased aortic stiffness assessed by pulse wave velocity in apolipoprotein E-deficient mice.
(54/1622)
Atherosclerosis develops and progresses spontaneously in apolipoprotein E-knockout (apoE-KO) mice. A direct consequence of atherosclerosis is an increase in vascular stiffness. Pulse wave velocity (PWV) has been used to assess the stiffness of large vessels and was found to be increased in patients with atherosclerosis. In the present study, aortic stiffness was assessed by PWV in 4- and 13-mo-old apoE-KO mice and age-matched controls (C57BL/6J). In 13-mo-old apoE-KO mice with extensive atherosclerotic lesions in the aorta (61 +/- 4%), PWV increased significantly (3.8 +/- 0.2 m/s) compared with controls (2.9 +/- 0.2 m/s). Endothelial nitric oxide (EDNO)-mediated vasorelaxation in response to ACh was markedly diminished in the aortic rings isolated from 13-mo-old apoE-KO mice compared with age-matched controls. In contrast, in 4-mo-old apoE-KO mice with only moderate atherosclerotic lesions in the aorta (23 +/- 5%), there were no significant changes in PWV and EDNO-mediated relaxation compared with controls. Blood pressure was not different among the four groups of mice. There were no significant differences in endothelium-independent vascular responses to sodium nitroprusside among different groups investigated. Histological evaluation revealed focal fragmentation of the elastic laminae in the aortic walls of 13-mo-old apoE-KO mice. These results demonstrate for the first time that aortic stiffness determined by PWV increases in 13-mo-old apoE-KO mice. Endothelial dysfunction and elastic destruction in vascular wall caused by atherosclerosis may have contributed. (+info)
Muscle metaboreflex control of cardiac output and peripheral vasoconstriction exhibit different latencies.
(55/1622)
Experiments were designed to determine 1) the mechanisms mediating metaboreflex-induced increases in systemic arterial pressure (SAP) in response to total vascular occlusion of hindlimb blood flow [e.g., increases in cardiac output (CO) vs. peripheral vasoconstriction] and 2) whether the individual mechanisms display differential latencies for the onset of the responses. Responses were observed in seven dogs performing steady-state treadmill exercise of mild and moderate workloads (3.2 km/h at 0% grade and 6.4 km/h at 10% grade). Differential latencies were exhibited among CO, nonischemic vascular conductance (NIVC; conductance to all nonischemic vascular beds), and renal vascular conductance (RVC), with peripheral vasoconstriction significantly preceding metaboreflex-mediated increases in CO. In addition, the latencies for SAP were not different from those for NIVC or RVC at either workload. During the lower workload there were small increases and then subsequent decreases in CO before the metaboreflex-induced increase in CO, which did contribute somewhat to the initial increases in SAP. However, the increases in CO mediated by the metaboreflex occurred significantly later than the initial increases in SAP. Therefore, we conclude that the substantial metaboreflex-mediated pressor responses that occur during the initial phase of total vascular occlusion during mild and moderate exercise are primarily caused by peripheral vasoconstriction. (+info)
The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques.
(56/1622)
Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. However, their role in modulating platelet function has not been shown. We studied the direct effect of chemokines on human platelets and found that of the 16 tested only stromal cell-derived factor (SDF)-1 induced platelet aggregation, accompanied by a rise in intracellular calcium. Platelets expressed the SDF-1 receptor, CXCR4, and an antibody to CXCR4 and pertussis toxin inhibited SDF-1-induced platelet aggregation, confirming that this effect is mediated through CXCR4, a Galphai-coupled receptor. SDF-1-induced platelet aggregation was also inhibited by wortmannin, LY294002, and genistein, suggesting that phosphatidylinositol 3-kinase and tyrosine kinase are likely involved in SDF-1-induced platelet aggregation. Because chemokines are produced from multiple vascular cells and atherosclerotic vessels are prone to develop platelet-rich thrombi, we examined the expression of SDF-1 in human atheroma. SDF-1 protein was highly expressed in smooth muscle cells, endothelial cells, and macrophages in human atherosclerotic plaques but not in normal vessels. Our studies demonstrate a direct effect of a chemokine in inducing platelet activation and suggest a role for SDF-1 in the pathogenesis of atherosclerosis and thrombo-occlusive diseases. (+info)