Thoracic Abdominal Aorta Research Articles

A case of Takayasu's arteritis and thoracic-abdominal pseudoaneurysm with vertebral destruction.

A 27-year-old woman presented to our institution with diagnosis of Takayasu’s arteritis and thoracic-abdominal pseudoaneurysm with vertebral destruction. Computed tomography revealed a giant 8 × 8 × 14 cm pseudoaneurysm with erosions of thoracic vertebrae 10, 11, and 12 (Figure 1 Panel A to C show CT image reconstruction; yellow arrow shows the pseudoaneurysm; arrow in Panel B shows the vertebral erosions in Figure 1 Panel C shows the ventral compensatory circulation caused by severe stenosis of the aorta). After a 4-week corticosteroid therapy, the descending thoracic-abdominal aorta grafting was performed. Intraoperatively serious vertebral body erosion was observed. More interestingly, the erosions on intervertebral disc were relatively mild which was rarely mentioned before (Figure 1 Panel D shows the direct vision of vertebral destruction; arrow shows the residual intervertebral disc). It suggested that compared with well-vascularized vertebral body, the avascular intervertebral disc with intact fibrous ring showed better erosion resistance. Considering this patient’s general condition, vertebral reconstruction was performed 3 weeks later, and patient discharged uneventfully in 2 weeks.

Hypoplasia of pulmonary artery's left branch and thoracic-abdominal aorta in a young athlete with Perthes disease

Hypoplasia of pulmonary artery's left branch and thoracic-abdominal aorta in a young athlete with Perthes disease

The effects of DeBakey type acute aortic dissection and preoperative peripheral and cardiac malperfusion on the outcomes after surgical repair.

IntroductionEmergent surgical repair of DeBakey type I and II acute aortic dissection represents the standard of care to prevent lethal complications.AimEvaluation of the effect of extension of aortic dissection (AAD) according to DeBakey classification, type I and II AAD, and the relationship with preoperative peripheral and myocardial malperfusion on early outcome and the mid-term follow-up period.Material and methodsA total of 135 patients who underwent AAD surgery between January 2015 and October 2019 were analysed.ResultsIn total 103 patients were affected by DeBakey type I AAD and 32 by DeBakey type II; 56 patients preoperatively showed peripheral, cardiac malperfusion, or both. Intra-operative mortality was 11%. Postoperative peripheral, cardiac malperfusion, and intraoperative and postoperative mortality were lower for type II AAD. The protective factor for intra- and postoperative 60-day mortality was type II AAD (RR = 0.03, p = 0.001); independent predictors were hypertension, and preoperative cardiac and renal-visceral malperfusion. At 5 years the overall survival was 74 ±6.9%. Independent predictors of reduced survival were major extension of type I AAD (RR = 5.37, p < 0.05) and preoperative cardiac malperfusion (RR = 5.78, p < 0.05). Five-year freedom from cardiac death, redo surgical operation, and new vascular procedures on the thoracic and abdominal aorta was 92 ±5.7%, 99 ±1.2%, and 81 ±7.2%, respectively. Extension of DeBakey type I AAD into the thoracic-abdominal aorta segment was also a predictor of the need for new vascular procedures (RR = 1.66, p = 0.05).ConclusionsA more favourable anatomy of DeBakey type II AAD is associated with better early and late outcomes after aortic repair. This is due to a lower incidence of peripheral and cardiac malperfusion.

Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function.

Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency. Cx47 is dispensable for long-chain fatty acid absorption from the gut but rather promotes serum lipid handling as prolonged elevated triglyceride levels were observed in Cx47-deficient mice after oral lipid tolerance tests. When crossed with Apolipoprotein E-deficient (Apoe-/-) mice, LDL-cholesterol was decreased in young Cx47-/-Apoe-/- adults as compared to Apoe-/- mice, which was inverted later in life. Finally, advanced atherosclerotic plaques in thoracic-abdominal aortas of 15 months-old mice tended to be larger in Cx47-/-Apoe-/- mice. These plaques contained fewer macrophages but similar amounts of T lymphocytes, collagen and lipids than plaques of Apoe-/- mice. In conclusion, Cx47 is expressed in lymphatic endothelium and seems modestly implicated in multiple aspects of lymphatic pathophysiology.

Registro de actividades de la Sociedad Española de Angiología y Cirugía Vascular, año2014

ObjectiveTo describe the health-care activities carried out by Angiology and Vascular Surgery Departments/Units in Spain in 2014. Patients and methodsCross-sectional study using a questionnaire sent to 107 centres on surgical procedures and vascular examinations performed in 2014. A descriptive analysis of results and comparison of the activity ratio/100,000 population with 2013 is also presented. ResultsResponses were received from 72 department (35 of them teaching), corresponding to 78 centres. In 2014 there were 44,295 admissions, of which 32.2% were emergency and 67.8% were elective, with a mean hospital stay of 7.3 days. The waiting list on December, 31st 2014 showed a predominance of venous rather than arterial disease (13,446 vs. 1,890). Arterial surgery in 2014 was similar to 2013, with some differences in the ratios/100,000 population: 9.4 vs. 10.3 in the supra-aortic trunk, 1.2 vs. 1.5 in the thoracic aorta, 0.38 vs. 0.31 in the thoracic-abdominal aorta, 1.3 vs. 1.4 in visceral arteries, 9.9 vs. 9.4 in the abdominal aorta, 11.2 vs. 11.4 in the aortic-iliac segment, 22.0 vs. 21.4 in the femoral-popliteal segment, and 9.0 vs. 9.4 in the distal segment. The ratio of conventional surgical procedures was lower for all of these, whereas that of endovascular surgery increased in some cases. Compared to 2013, there was similar number of haemodialysis access procedures performed in 2014 (20.6 vs. 19.9). Procedures involving major and minor amputations were similar (7.4 vs. 7.6, 10.8 vs. 11.3, respectively). The overall venous surgery activity in 2014 was similar to 2013 (65.4 vs. 67.4), although there were more procedures using endovascular surgery. The ratio/100,000 population of vascular examinations was similar to 2013 (760.5 vs. 764.1). ConclusionThe activity was stable in 2014 compared to 2013, in almost the whole area of arterial surgery, although endovascular procedures increased in some vascular areas. Venous surgery on the whole has remained, with similar number of procedures, despite that the varicose treatments significantly increased in endovascular procedures. Vascular examinations maintained a similar activity to 2013.

Abstract 19240: Operative Indication for Chronic Dissecting Aneurysm in Descending Thoracic and Thoracoabdominal Aorta

Background: Because of a lack of information about the rupture size of chronic dissecting descending thoracic and thoracoabdominal aneurysms, we evaluated the natural history of those aneurysms. Patiens and Methods: Data on 422 patients (mean age, 63.3 ± 11.3; 272 male) with chronic dissection in descending thoracic and thoracoabdominal aorta treated at our institution from 2007 to 2014, were analyzed. Patients with connective tissue disorder, impending rupture of aneurysms, infected aneurysms, and an acute dissection without aneurysms were excluded. Chronic dissection was defined as a dissection more than 2 weeks from symptom onset. The aneurysm diameter at the time of the rupture was measured on CT scan in ruptured aneurysms group (n=21), and initial aneurysmal diameter on CT scan in non-ruptured aneurysms group (n=401). The measurements were performed at maximum short axis diameter of the aneurysm on three-dimensional CT. Results: Midian size of all aneurysms was 4.5 cm (range 3.5 to 9.0 cm) and that of in ruptured aneurysms was 5.9 cm (range 4.5-8.0 cm). The location of aneurysms was descending aorta in 303 patients, thoracoabdominal aorta in 119. Aortic surgery was performed in 150 patients (urgent in 20, elective in 130). Hospital mortality rate were 20% (5/20) in patients with ruptured aneurysms and 2.3% (3/130) in patients with non-ruptured aneurysms. Figure shows the incidences of rupture according to the aneurysm size. The incidence of a rupture increases with larger aortic size. At 3.5 to 3.9 cm, 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm and more than 6.0 cm, the incidence of rupture was 0%, 0%, 1.2%, 10.2%, 14.3% 20.8%, respectively. The aneurysms more than 5.0 cm were ruptured in 15.1% of patients. Conclusions: Because an elective operation is associated with low mortality, operative indication of chronic dissecting aneurysm in descending and thoracic-abdominal aorta should be considered when its size is 5.0 cm or larger in good-risk patients.

Abstract 18661: Regulation of Lymphatic Physiology by Connexin47

Introduction: Mutations in GJC2, which encodes connexin47 (Cx47), are associated with lymphedema. Moreover, Cx47 mRNA was recently found in human lymphatic endothelial cells (LECs). Hypothesis: Lymphatic endothelial Cx47 has a role in lymphatic physiology and pathology. Methods: Confocal microscopy and qPCRs were used to assess expression of Cx47. Lymphatic drainage was studied by subcutaneous Evans Blue injections in the footpad of 12 week-old ApoE -/- or Cx47 eGFP/eGFP ApoE -/- mice. Atherosclerosis was studied in 15 months-old ApoE -/- or Cx47 eGFP/eGFP ApoE -/- mice. Results: Cx47 was expressed in lymphangions of mesenteric collecting vessels in Cx47 eGFP/eGFP Prox1-mOrange2 mice as assessed by microscopy and its expression was confirmed by qPCR on mesentery, gut and skin mRNA of ApoE -/- but not Cx47 eGFP/eGFP ApoE -/- mice. Interestingly, lymphatic drainage was enhanced in Cx47-deficient mice (n=10/11, p&lt;0.05). To address whether Cx47 affects chronic immuno-inflammatory pathology atherosclerotic plaque formation was studied in 15-month old male ApoE -/- and Cx47 eGFP/eGFP ApoE -/- mice on regular chow. These studies showed that Cx47-deficiency does not affect the size or composition (e.g. lipid, collagen or macrophage content) of aortic plaques in the aortic root. However, plaque development in the thoracic-abdominal aorta of 15 months-old mice tended to be larger in Cx47 eGFP/eGFP ApoE -/- mice (21±5 vs 30±4 % lipid area, n=10, p=0.08). Unexpectedly, total cholesterol (TC) and LDL, but not HDL, triglycerides or free fatty acids, were increased in serum of Cx47 eGFP/eGFP ApoE -/- mice as compared to ApoE -/- serum (TC: 472±24 vs 647±18 mg/dL, n=10, p&lt;0.01; and LDL: 272±20 vs 443±17 mg/dL, n=10, p&lt;0.001, respectively). Increased lymphatic drainage from plaques in Cx47 eGFP/eGFP ApoE -/- mice may, partially, compensate for increased serum TC and LDL thereby preventing exuberant atherosclerotic plaque formation despite increased serum lipid levels. Conclusions: In conclusion, Cx47 is expressed in LECs of the lymphangion and seems implicated in multiple aspects of lymphatic (patho)physiology.

Registro de actividades de la Sociedad Española de Angiología y Cirugía Vascular, año 2013

ObjectiveTo describe the health-care activities carried out by the Services/Units of Angiology and Vascular Surgery in Spain in 2013. Patients and methodsCross-sectional study with a survey of 92 centres on surgical procedures and vascular examinations performed in 2013. Descriptive analysis was performed on the results and a comparison was made on the ratio of activity/100,000 population with 2012. ResultsResponses were received from 69 services (34 teaching services), corresponding to 75 centres. In 2013 there were 49,206 admissions, of which 36.8% were emergencies and 63.2% were elective, with a mean stay of 7.2 days. As of 31 December 2013, the waiting list showed a predominance of venous over arterial pathology (12,410 vs. 2,199). Arterial surgery in 2013 was lower than in 2012, with the following ratios/100,000 population: 10.3 vs. 12.1 in the supra-aortic trunk, 1.5 vs. 1.4 in the thoracic aorta, 0.31 vs. 0.33 in the thoracic-abdominal aorta, 1.4 vs. 1.9 in visceral arteries, 9.4 vs. 9.7 in the abdominal aorta, 11.4 vs. 23.1 in the aorto-iliac segment, 21.4 vs. 20.9 in the femoro-popliteal segment, and 9.4 vs. 13.7 in the distal segment. For all of these, the ratio of conventional surgical procedures was lower, whereas that of endovascular surgery increased in some cases. In 2013 fewer haemodialysis access procedures were performed (19.9 vs. 24.0). Procedures involving major and minor amputations and diabetic foot debridement were similar (7.6 vs. 7.3, 11.3 vs. 11.4 and 5.6 vs. 5.6, respectively). Varicose vein procedures in 2013 were the same as in 2012 (both with a ratio of 66.1/100,000 population), although there were more procedures using conventional surgery and fewer with endovascular surgery. The ratio/100,000 population of vascular examinations was higher in 2013 (764.1 vs. 697.8). ConclusionAs compared to 2012, arterial surgery has decreased overall, and endovascular procedures have increased in some areas. Overall, venous surgery has remained the same, with a reduction in endovascular procedures. Vascular examinations have increased.

60: Atherosclerosis severity is independent of endogenous IL-33 signaling

Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work demonstrated that the systemic administration of IL-33 reduces the development of atherosclerosis in the apolipoprotein E-deficient (ApoE −/− ) mouse model of the disease by induction of a Th1-to-Th2 shift. However, the role of endogenous IL-33 in the atherogenesis remains elusive. Atherosclerosis was induced in 10 week-old ApoE −/− , IL-33 −/− ApoE −/− and ST2 −/− ApoE −/− mice by feeding a high-cholesterol diet (1.25%, no cholate) for 10 weeks. Additionally, a group of ApoE −/− mice were injected with a neutralizing anti-ST2 antibody or an isotype control during the period of the diet. The atherosclerotic lesion development was measured with Oil Red O in the thoracic-abdominal aorta and in the aortic sinus. The mRNA levels of several cytokines, including IL-6, IFN γ , IL-17, IL-5 and IL-10 were assessed in the aorta and in in vitro -stimulated lymph node cells. We observed no differences in lipid-staining area in the aortas of IL-33 −/− ApoE −/− mice (8.84 ± 0.97; mean ± SEM; n = 9–25), ST2 −/− ApoE −/− mice (6.95 ± 0.78), ApoE −/− mice untreated (7.05 ± 0.78), ApoE −/− mice injected with either the neutralizing anti-ST2 antibody (6.08 ± 0.79) or the isotype control (6.16 ± 0.86) after high-cholesterol diet feeding. Similar results were obtained in the aortic sinus compared to ApoE −/− controls. Total serum cholesterol and triglyceride levels were not different compared to ApoE −/− controls. IL-33 expression in aortic tissue was comparable in ApoE −/− and ST2 −/− ApoE −/− mice and absent in IL-33 −/− ApoE −/− mice. There was no difference in the transcript levels of inflammatory cytokines in the aorta and in in vitro -stimulated lymph node cells. These data indicate that in contrast to the anti-atherosclerotic effect of systemically administered recombinant IL-33, the endogenously produced cytokine and its receptor do not significantly influence the severity of atherosclerosis in ApoE-deficient mice fed with a high-cholesterol diet.

Pharmaceutical stabilization of mast cells attenuates experimental atherogenesis in low-density lipoprotein receptor-deficient mice

Mast cells (MCs) contribute to atherogenesis by releasing pro-inflammatory mediators to activate vascular cells and other inflammatory cells. This study examined whether MC activation or stabilization affects diet-induced atherosclerosis in low-density lipoprotein receptor-deficient (Ldlr–/–) mice. When Ldlr–/– mice consumed an atherogenic diet for 3 or 6 months, MC activation with compound 48/80 (C48/80) increased aortic arch intima and total lesion areas, and plasma total cholesterol, LDL, and triglyceride levels, whereas MC stabilization with cromolyn reduced these parameters. There were significant differences in arch intima and total lesion areas, and plasma total cholesterol, LDL, and triglyceride levels between C48/80-treated and cromolyn-treated mice. To examine a therapeutic application of cromolyn in atherosclerosis, we fed Ldlr–/– mice an atherogenic diet for 3 months followed by giving mice cromolyn for additional 3 months. Cromolyn did not affect aortic arch intima area, but significantly reduced lipid deposition in the thoracic-abdominal aortas. In aortic arches, however, cromolyn treatment significantly reduced lesion contents of Mac-3+ macrophages, CD4+ T cells, activated MCs, and lesion cell proliferation. While plasma total cholesterol and LDL levels increased and high-density lipoprotein (HDL) levels decreased from 3 months to 6 months of an atherogenic diet, cromolyn treatment decreased significantly plasma total cholesterol, LDL, and triglyceride levels and increased HDL levels above those of 3-month time point. These observations demonstrate that MC stabilization reduces lesion inflammation, ameliorates plasma lipid profiles, and may serve as a potential therapy for this cardiovascular disease.

Super, red palm and palm oleins improve the blood pressure, heart size, aortic media thickness and lipid profile in spontaneously hypertensive rats.

BackgroundOleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension.Methodology/Principal FindingsFour-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (p<0.001), 178.9±2.7 mmHg (p<0.001) and 167.7±2.1 mmHg (p<0.001), respectively, compared with SHR controls (220.9±1.5 mmHg). Bradycardia was observed with SO and PO. In contrast, the SBP and heart rate of treated WKY rats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR.ConclusionThe SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR.

Rusults of Classical Crawford and Hybrid Operations in Thoracic-Abdominal Aorta Aneursysms Treatment - Comperative Assesment

Thoracic-abdominal aortic aneurysms (TAAA) are still serious medical problem. Classical procedure requires two cavities approach and implantation of vascular prosthetic in the place of aneurysm--Crawford's procedure. Significant progress was made during last years by using endovascular procedures (stentgrafts). Alternative is hybrid procedure--prosthetic appliance of visceral and kidney arteries and then stentgraft implantation in whole thoracic-abdominal aorta. THE AIM OF THE STUDY was comparative analysis of classical and hybrid procedures in thoracic-abdominal aneurysms treatment. Between 1989-2011 in Department of Vascular, General and Transplantological Surgery Medical University in Wrocław and Surgical Department of 4th Military Clinical Hospital in Wrocław 53 patients were operated due to thoracic-abdominal aortic aneurysms. Classical Crawford's procedure was performed in 41 patients (group I) and hybrid procedure was performed in 12 patients (group II). Additionally 7 patients required aortic arc branches reconstruction due to achieve optimal conditions to stentgraft amplantation. Procedures were performed at one or two stages. Mortality in patients treated classically (group I) depended on type of aneurysm in Crawford's classification. In type I-II mortality rate was 54% ((7 deaths/12 patients), in type III do V 17% (5 deaths/ 29 patients). In the group after hybrid procedure (group II) mortality rate was 28% (2 deaths/ 7 patients) in type I-II and 20% (1 death/5 patients) in type III to V. Observed serious perioperative complications. 1. Endovascular procedures development enabled introducing of new methods in thoracic-abdominal aortic aneurysms treatment (hybrid procedures) and allowed to get better results. 2. Clear advantage of hybrid procedures above classical Crawford's procedure is observed in type I and II of TAAA. 3. Mortality and morbidity rates recommend hybrid procedure in type I and II of TAAA. 4. Surgical results of classical and hybrid procedures in type III-V TAAA treatment are comparative, with indication on classical approach.

The arterial load in pulmonary hypertension.

The anatomical differences between the pulmonary and systemic arterial system are the main cause of the difference in distribution of compliance. In the pulmonary arterial system compliance is distributed over the entire arterial system, and stands at the basis of the constancy of the RC-time. This distribution depends on the number of peripheral vessels, which is ∼8-10 times more in the pulmonary system than the systemic tree. In the systemic arterial tree the compliance is mainly located in the aorta (80% of total compliance in thoracic-abdominal aorta). The constant RC-time in the pulmonary bed results in proportionality of systolic and diastolic pressure with mean pressure and, in turn, in the constant ratio of oscillatory and mean power.

Abstract 5064: Endothelial-Specific Deletion of Cx40 Promotes Atherosclerosis by Increasing CD73-Dependent Leukocyte Adhesion

Endothelial dysfunction is the initiating event of atherosclerosis. The expression of connexin40 (Cx40), an endothelial gap junction protein, is decreased during atherogenesis. Here, we sought to determine whether Cx40 contributes to the development of the disease. Mice with ubiquitous deletion of Cx40 are hypertensive, a risk factor for atherosclerosis. Consequently, we generated atherosclerosis-susceptible mice with endothelial-specific deletion of Cx40 (Tie2CRE+ Cx40fl/fl ApoE−/− mice; EC-Cx40del mice). EC-Cx40del mice were indeed not hypertensive. The progression of atherosclerosis was increased in EC-Cx40del mice after 10 weeks high-cholesterol diet; lipid deposition in the thoracic-abdominal aortas was 21.4±3.5% (N=10, p&lt;0.01) in EC-Cx40del mice as compared to 12.6±1.3% for Tie2CRE+ Cx40wt/wt ApoE−/− and 7.1±1.3% for Tie2CRE- Cx40fl/fl ApoE−/− controls. Moreover, spontaneous lesions were observed in the aortic sinuses of young EC-Cx40del mice without diet. These lesions showed monocyte infiltration into the intima, increased expression of VCAM-1 and decreased expression of the ecto-enzyme CD73 in the endothelium. The pro-inflammatory phenotype of EC-Cx40del mice was confirmed in another model of induced leukocyte recruitment from the lung microcirculation. The number of leukocytes that migrated to the alveolar space in response to intratracheal instillation of LPS was markedly enhanced (p&lt;0.001) in EC-Cx40del mice compared to controls, both 3 and 6 hours after the treatment. Endothelial CD73 is known to induce anti-adhesion signaling via the production of adenosine. We found that reducing Cx40 expression in vitro with siRNA or anti-sense decreased CD73 expression and activity, and increased leukocyte adhesion to mouse endothelial cells (p&lt;0.01). These effects were reversed by an adenosine receptor agonist. A control siRNA or Cx40 sense had no effect on leukocyte adhesion. We suggest that Cx40-mediated gap junctional communication contributes to a quiescent non-activated endothelium by propagating adenosine-evoked anti-inflammatory signals between endothelial cells. Alteration in this mechanism by targeting Cx40 promotes leukocyte adhesion to the endothelium, thus accelerating atherosclerosis.

Abstract 3716: Endothelial-specific Deletion Of The Gap Junction Protein Connexin43 Reduces Atherosclerosis In Mice

Decreasing the expression of the gap junction protein connexin43 (Cx43) in mice provides beneficial effects on both the progression and composition of the atherosclerotic lesions. During atherosclerotic lesion development, Cx43 expression is temporarily up-regulated in intimal smooth muscle cells, induced in macrophages close to the lipid core and triggered in a subset of endothelial cells covering the shoulder of atherosclerotic lesions. The purpose of this study was to examine the role of endothelial Cx43 in the development of atherosclerosis in vivo. For this purpose, we have used the Cre-loxP system to create an atherosclerosis-susceptible mouse line in which Cx43 is deleted from the endothelium only. The natural progression of atherosclerosis and the composition of the atherosclerotic lesions were studied in 18 month-old male TIE2Cre+ Cx43fl/fl ApoE−/− mice and TIE2Cre- Cx43fl/fl ApoE−/− littermate controls. Body weights were not different between both groups. Interestingly, the progression of atherosclerosis (measured as % of surface stained with Sudan IV) was significantly reduced in the thoracic-abdominal aorta of TIE2Cre+ Cx43fl/fl ApoE−/− mice (21.53±7.14%; N=4) compared with TIE2Cre- Cx43/fl/fl ApoE−/− controls (46.84±11.60%, N=6, P&lt;0.05). In addition, advanced atheroma in TIE2Cre+ Cx43fl/fl ApoE−/− mice contained less lipids and showed decreased calcium deposition compared with lesions in TIE2Cre- Cx43fl/fl ApoE−/− controls. Thus, endothelial-specific deletion of Cx43 in mice provides beneficial effects on both the natural progression and composition of the atherosclerotic lesions. Future studies are aimed at obtaining insight into the participation of Cx43 in macrophages and smooth muscle cells in atherosclerosis.

Studies on angiotensin I converting enzyme (ACE): inhibitory effect of imidapril, a novel ACE inhibitor (II). Inhibition of various tissue ACEs ex vivo

The antihypertensive mechanism of imidapril was investigated in relation to its inhibition of ACE activities in the serum, thoracic-abdominal aorta, lung, kidney, heart and brain from adult spontaneously hypertensive rats (SHRs). In comparison with normotensive rats (NTRs), the ACE activities in the aorta, heart, brain and lung were higher, while those in the serum and kidney were considerably lower. Imidapril (2 mg/kg) showed remarkable inhibitions within 6 hr in all tissues, except for the brain, after a single oral administration. Consecutive administration of imidapril (2 mg/kg/day) for 30 days produced inhibitions in all tissues. The inhibitions in the serum, aorta and lung were greater, and the duration of inhibition in the aorta, brain and lung were longer. Blood pressure declined gradually until 6 hr, and the reductions were significant at 24 hr after the single and chronic administrations. Imidapril (0.5 mg/kg, ineffective on normal blood pressure) inhibited ACE activities in NTRs similarly. Enalapril at the same dose exhibited less ACE inhibition and antihypertension. These results suggest that the ACE inhibition in the serum, lung and aorta by imidapril correlate with the antihypertension in SHRs; especially, the lung and vascular ACE inhibitions play an important role in the duration of antihypertension in SHRs.

Noninvasive assessment of lipid disposition in treated and untreated atherosclerotic rabbits.

In an effort to visualize whole body cholesteryl ester (CE) deposition using the nuclear medicine imaging technique of gamma camera scintigraphy, 125I-cholesteryl iopanoate (125I-CI), a nonhydrolyzable CE analogue, was used as a marker for CE deposition in atherosclerotic New Zealand white rabbits. Groups of animals were fed either a cholesterol-enriched diet (2%, w/w) or the same diet supplemented with the hypolipidemic drugs colestipol (1%, w/w) and/or clofibrate (0.3%, w/w). Injections of 125I-CI were administered biweekly. At the end of 15 weeks, animals were scintigraphically scanned and sacrificed for tissue analysis. The results demonstrated that while drug treatment had no significant effect on plasma lipid levels, it substantially lessened atherosclerotic involvement in the thoracic-abdominal aorta. These differences in aortic lipid accumulation were reflected in the whole-body scans which showed a reduction in tissue accumulation of 125I-CI in the drug-treated groups. Gamma camera scintigraphy thus represents a rapid means of visualizing tissue CE accumulation which could facilitate the evaluation of lipid-lowering drug efficacy and possible antiatherosclerotic effect.