Angiotensin 1-7, but not the thrombin-cleaved osteopontin C-terminal fragment, attenuates osteopontin-mediated macrophage-induced endothelial-cell inflammation.

OBJECTIVE AND DESIGN: Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1-7. MATERIAL AND SUBJECTS: Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages. TREATMENT: Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1-7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1-7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation. METHODS: Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay. RESULTS: Conditioned media of macrophages treated with OPN-C induced hcECs' NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1-7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines. CONCLUSIONS: OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1-7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.

Low Osteopontin N-Terminal Fragment and Carotid Plaque Stability Associated with Statin or Antiplatelet Therapy.

INTRODUCTION: Full-length osteopontin (OPN-FL), whose levels are elevated in association with atherosclerosis, is cleaved by thrombin, resulting in the formation of a putatively biologically-active N-terminal cleavage product (OPNN). This study addresses the hypothesis that statin and antiplatelet therapy in hypertensive patients specifically reduces OPN-N, rather than OPN-FL, in carotid plaques. METHODS: Seventy-four carotid plaques were collected from patients who underwent carotid endarterectomy (CEA). Plaque tissue was used to measure OPN proteins and for histological and immunohistochemical characterization. RESULTS: There were 22 statin-negative and 52 statin-treated patients. In the carotid plaque, immunohistochemical staining for macrophages was higher in statin-negative vs. statin-treated patients (high CD68 immunostaining was in 61.9 vs. 28.6%, p=.03, respectively). OPN-FL staining had a similar trend, but without statistical significance (78.7 vs. 47.8%, p=.08, respectively). Western blot analysis of plaque OPN-FL showed that statin treatment was not associated with significant alteration of its abundance, but with a significantly lower plaque content of OPN-N [median 0.08 (IQR 0.05-1.01) vs. 0.81 (IQR 0.27-2.86), respectively, p=.015]. Comparable pattern of association between OPN proteins and antiplatelet therapy was found: the abundance of OPN-FL was not different in plaques from untreated or treated patients, while the abundance of OPN-N was significantly reduced in antiplatelet treated vs. non-treated patients [0.08, (IQR 0.05-0.66) vs. 0.89, (IQR 0.13-1.94), p=0.004]. CONCLUSION: The effect of anti-atherosclerotic treatment on carotid plaques of hypertensive patients more readily associates with OPN-N than with OPN-FL expression, suggesting that anti-atherosclerotic treatment including statins and antiplatelet drugs modulates the "OPN system".

N-terminal rather than full-length osteopontin or its C-terminal fragment is associated with carotid-plaque inflammation in hypertensive patients.

BACKGROUND: Hypertensive patients develop carotid atherosclerotic plaques with enhanced inflammation. Full-length osteopontin (OPN-FL), a multifunctional protein whose levels are elevated in association with atherosclerosis, is cleaved by thrombin and matrix metalloproteinases to form a C-terminal and a putatively biologically active N-terminal fragment (OPN-C, OPN-N, respectively). We conducted a study to examine whether plaque inflammation in hypertensive patients corresponds to the expression of OPN or of its cleaved forms or both. METHODS: We collected 42 carotid plaques from 41 consecutive hypertensive patients during carotid endarterectomy. Plaque tissue was used to measure matrix metalloproteinase-12 (MMP-12) and OPN proteins, and for the classification of plaques as showing low- or high-degree inflammation through histological and immunohistochemical evaluation. RESULTS: Fifteen highly inflamed plaques and 27 plaques with characteristics of low-grade inflammation were collected. Moderate to heavy staining for OPN characterized 87% of the plaques with high-degree inflammation but only 44% of those with low-degree inflammation, corresponding to the percentages of plaques that were heavily stained for the macrophage marker CD68 (93% versus 26%, respectively, P < 0.01). Western blot analysis showed that the abundance of OPN-FL and OPN-C was comparable in the two groups. However, the abundance of OPN-N was significantly greater in the highly inflamed plaques (median, 3.8 (range, 0.8-7.3) vs. median, 0.9 (range, 0.2-1.5); P = 0.017, respectively). The abundance of MMP-12 was significantly greater in the high- than in the low-degree plaque inflammation group (4.8 (range 1.9-8.8) vs. 1.1 (range 0.3-1.4), respectively; P = 0.03). CONCLUSIONS: The N-terminal fragment of osteopontin, rather than OPN-FL or OPN-C, is associated with carotid plaque inflammation in hypertensive patients. Future studies should assess whether targeting OPN cleavage could present a new approach to preventing high-risk carotid plaques.

Does percutaneous transluminal renal artery angioplasty improve blood pressure control and renal function in patients with atherosclerotic renal artery stenosis?

BACKGROUND: Percutaneous angioplasty (PTA) and stenting is an established procedure for the treatment of hypertension caused by atherosclerotic renal artery stenosis. However recently, the decision whether or notto perform this procedure has raised considerable debate. OBJECTIVES: To examine the association between the basic clinical and radiological characteristics of candidates for renal artery PTA and the clinical outcome of the procedure in terms of improvement of blood pressure control and renal function. METHODS: We conducted a retrospective cohort study of all patients who underwent percutaneous transluminal renal artery angioplasty (PTRA) and stent implantation in a tertiary medical center during the period 2000-2007. The clinical and radiological data were extracted from the medical file of each patient. Blood pressure measurements and creatinine level were recorded before the procedure and 1 month, 6 months, 12 months and 18 months after PTRA. RESULTS: Thirty-two patients were included in the final statistical analysis. The mean age of the study population was 66.6 +/- 8.8 years old and 75% were men. There was a significant reduction in both systolic and diastolic blood pressure 1 month after the procedure: 160.5 +/- 24.7 vs. 141.8 +/- 23.6 mmHg and 83.8 +/- 12.9 vs. 68.8 +/- 11.8 mmHg respectively (P < 0.001). The reduction in blood pressure was constant throughout the follow-up period and was evident 18 months after the procedure: 160.5 +/- 24.7 vs. 135.0 +/- 35.1 mmHg and 83.8 +/- 12.9 vs. 71.3 +/- 16.5 mmHg respectively (P < 0.001). However, no improvement in renal function was observed at any time during the follow-up period. We could not demonstrate an association between clinical or radiological features and the clinical outcome after PTRA. CONCLUSIONS: Our findings show that PTRA can be considered an effective procedure for improving blood pressure control in patients with atherosclerotic renal artery stenosis (ARAS) and resistant hypertension. This research, together with previous studies, strengthens the knowledge that the decline in glomerular filtration rate seen in many patients with ARAS is non-reversible and is not improved by PTRA.

Nailing before vascular repair in tibial fracture with associated arterial injury.

The incidence of arterial injuries in extremity fractures is approximately 1% to 2%. In patients with combined vascular and orthopedic injury but without a mangled extremity, the decision whether to give priority to the fracture fixation or to the vascular repair is still somewhat controversial. We successfully used the unreamed tibial nail before the arterial repair when treating an open tibial shaft fracture associated with a torn anterior tibial artery and present it as an illustrative case for the method. Fracture alignment was achieved manually and an unreamed tibial nail was introduced. The nail was secured only proximally by two interlocking screws inserted through jig. The procedure provided good alignment and length for end-to-end reconstruction of the anterior tibial artery. The distal interlocking screws were inserted at the end of vascular reconstruction.

Primary aortoduodenal fistula: Pitfalls and success in the endoscopic diagnosis.

Primary aortoenteric fistula is a rare but catastrophic cause of gastrointestinal bleeding. The diagnosis of primary aortoenteric fistula is difficult to make and is usually accompanied by a very high level of clinical suspicion. It should be considered in any elderly patient presenting with upper gastrointestinal bleeding in the context of a known abdominal aortic aneurysm. Prompt surgical intervention is necessary. We present the case of a 78-year-old man with a history of atherosclerotic abdominal aortic aneurysm which is presented with massive upper gastrointestinal bleeding due to a primary aortoduodenal fistula. Initial misdiagnosis led to a delay in treatment and the patient succumbed to the illness.

[Endovascular stent-graft repair of aorto-esophageal fistula causing upper gastrointestinal bleeding].

An 83 year old woman with massive upper GIT bleeding was diagnosed as having an aorto-esophageal fistula in the mid descending thoracic aorta which was mildly aneurysmatic and showed atheromatous changes. Past medical history reported Giant Cell Arteritis. Following endoscopy and evaluation using CT angiography, the patient underwent an endovascular stent graft repair of the thoracic aorta using a Talent stent graft. Recovery was uneventful and the patient recuperated. This case study discusses a possible common baseline pathology of the thoracic aortic aneurysm, the aorto-esophageal fistula and the Giant Cell Arteritis.

Duplex study of the carotid and femoral arteries of patients with rheumatoid arthritis: a controlled study.

BACKGROUND: "Ultrasonic biopsy" (U-B) is a noninvasive screening technique to detect early atherosclerotic plaques and arterial wall changes. AIM: To identify atherosclerosis (AS) in the common carotid artery (CCA) and common femoral artery (CFA) of patients with rheumatoid arthritis (RA) and their matched controls. METHODS: Fifty-seven consecutive RA patients were enrolled in the study. Controls were matched by age, sex, ethnicity, and AS risk factors. All patients and controls underwent U-B study of the CCA and CFA. The U-B features were classified and scored as follows: Class A, normal (score 0); Class B, interface disruption (score 2); class C, intima-media (I-M) granulation (score 4); Class D, plaque without hemodynamic disturbance (score 6); Class E, stenotic plaque (score 8); and Class F, plaque with symptoms (score 10). Total score per patient was calculated. Classes A-B indicate an intact media or minimal interphase changes; classes D-F point to a significant medial involvement. Class C signifies a borderline lesion, with a potential for regression to normal, being unchanged, or progression to a plaque. RESULTS: Mean ages were 52.1 years for RA and 51.4 years for controls (P = 0.81). Eighty-six percent of the patients and 85% of controls were women. The mean disease duration of RA was 12.8 years. Frequencies of risk factors among the RA patients compared with controls were hypertension (28% versus 32%), smoking (37% versus 29%), dyslipidemia (23% versus 25%), diabetes mellitus (DM) (14% versus 14%), and family history of cardiovascular disease (CVD) (4% versus 7%). Forty-five percent of the RA patients had at least a single Classes D-F lesion (plaque) in 1 of the 4 vessels tested, compared with 40% in the control group (P = 0.19). The mean total U-B scores of the RA patients and controls were not significantly different (8.87 versus 9.49, P = 0.7). Univariate analyses have shown that the development of plaques in RA patients was associated with age >50 years, disease duration, hypertension, dyslipidemia, and smoking. Multivariate analysis found plaques to be strongly associated with age above 50 years and dyslipidemia. CONCLUSION: In unselected RA patients, besides classic AS risk factors, older age and longstanding disease may help predict the development of a severe morphological expression of AS.

Duplex study of the carotid and femoral arteries of patients with systemic lupus erythematosus: a controlled study.

OBJECTIVE: To identify atherosclerosis in the common carotid (CCA) and common femoral arteries (CFA) of patients with systemic lupus erythematosus (SLE) and matched controls. METHODS: Fifty-one consecutive patients with SLE were enrolled in the study. Controls were matched by age, sex, ethnicity, and atherosclerosis risk factors. All patients and controls underwent ultrasonic biopsy (U-B) of the CFA and CCA, a noninvasive screening technique that detects early atherosclerotic plaques and changes. The U-B features were classified and scored as follows: class A: normal (score 0); class B: interface disruption (score 2); class C: intima-media granulation (score 4); class D: plaque without hemodynamic disturbance (score 6); class E: stenotic plaque (score 8); and class F: plaque with symptoms (score 10). Total score was calculated. Classes A and B indicate an intact media; classes D to F point to a significant medial involvement; class C signifies a borderline lesion with a potential for regression to normal or progression to a plaque. RESULTS: Mean ages were 40.5 years for SLE patients and 41 years for controls (p = 0.6). Ninety-six percent of the patients and controls were women. The mean disease duration of SLE was 8.65 years. Frequencies of risk factors among the SLE patients compared to controls were hypertension (30% vs 24%), smoking (23% vs 24%), and dyslipidemia (17.7% vs 17%). No patient had diabetes mellitus or family history of cardiovascular disease. A 3.17-fold increased rate of atherosclerotic plaques was detected in the SLE patients compared with controls (95% CI 1.08-10.9). Twenty-eight percent of SLE patients had at least a single class D-F lesion in one of the 4 vessels tested, compared with 10% in the control group (p = 0.02). In addition, the mean total U-B score of the SLE patients was significantly higher than that of the controls (5.65 vs 3.14; p = 0.02). Univariate analyses showed that the development of plaques in SLE was associated with a history of ischemic heart disease, hypertension, cardiovascular accident, and anemia. Multivariate analysis found plaques to be strongly associated with age, particularly in those older than 50 (OR 2.66, p = 0.000). CONCLUSION: Patients with SLE have a high rate of atherosclerotic changes compared to controls. The development of atherosclerosis is strongly associated with age.

The dilemma of immediate preoperative hypertension: to treat and operate, or to postpone surgery?

STUDY OBJECTIVE: To evaluate the efficacy and complications of immediate preoperative reduction of arterial blood pressure (BP) in patients with well-controlled hypertension but with diastolic blood pressure (DBP) between 110 and 130 mmHg on arrival at the operating room (OR). DESIGN: Prospective, randomized, large-sample study. SETTING: University-affiliated, 550-bed community hospital. PATIENTS: 989 patients with well-controlled hypertension, who were scheduled for surgery, and who had no previous myocardial infarction, unstable or severe angina pectoris, renal failure, pregnancy induced hypertension, left ventricular hypertrophy, previous coronary revascularization, aortic stenosis, preoperative dysrhythmias, conduction defects, or stroke. INTERVENTIONS: Patients with DBP between 110 and 130 mmHg were randomly allocated to two groups: 400 patients in the control group and 589 patients serving as the study group. The control group had their surgery postponed and they remained in hospital for BP control, and the study patients received 10 mg of nifedipine intranasally delivered. The patients were observed for cardiovascular and neurological complications during the intraoperative period and over the first three postoperative days. MEASUREMENTS AND MAIN RESULTS: The two groups were similar in age, gender, type of surgery, duration of anesthesia, and intraoperative fluid administration. There were no statistically significant differences in postoperative complications. The hospitalization time was considerable shorter in the study group than in the control group. CONCLUSIONS: Immediate preoperative reduction of DBP with intranasal nifedipine is safe in patients with well-controlled arterial hypertension but they presented with severe to very severe hypertension for patients in the OR. We were able to avoid unnecessary surgery postponement and attendant costs.

Malignant hypertension as a presenting symptom of Takayasu arteritis.

We present an unusual case of malignant hypertension in a 20-year-old white woman. One week before hospitalization, she experienced occasional abdominal pain and claudication of both legs; otherwise, she had no remarkable medical history, including no history of high blood pressure. The origin of the patient's hypertension was renovascular, and the vascular injury was due to vasculitis of the large arteries. The combination of a difference in blood pressure between the patient's arms, angiographic findings, elevated erythrocyte sedimentation rate, and lack of markers for specific vasculitis led to the diagnosis of Takayasu arteritis. Surgical intervention was successful.