Ubiquitin-proteasome overactivity is associated with enhanced inflammatory reaction in symptomatic plaques. The inhibition of ubiquitin-proteasome activity in lesions of symptomatic patients by rosiglitazone is associated with plaque stabilization, possibly by down-regulating NFkB-mediated inflammatory pathways.

Abstract-Whether morning blood pressure surge influences the molecular mechanisms of plaque progression toward instability is not known. Recently, we have demonstrated enhanced activity of the ubiquitin-proteasome system in human plaques and evidenced that it is associated with inflammatory-induced plaque rupture. We evaluated the inflammatory infiltration and ubiquitin-proteasome activity in asymptomatic carotid plaques of hypertensive patients with different patterns of morning blood pressure surge. Plaques were obtained from 32 hypertensive patients without morning blood pressure surge and 28 with morning blood pressure surge enlisted to undergo carotid endarterectomy for extracranial high-grade (Ͼ70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T-lymphocytes, human leukocyte antigen-DRϩcells, ubiquitin-proteasome activity, nuclear factor-B, inhibitor kB-␤, tumor necrosis factor-␣, nitrotyrosine, matrix metalloproteinase-9, and collagen content (immunohistochemistry and ELISA). Compared with plaques obtained from hypertensive patients without morning blood pressure surge, plaques from with morning blood pressure surge had more macrophages, T-lymphocytes, human leukocyte antigen-DRϩcells (PϽ0.001), ubiquitin-proteasome activity, tumor necrosis factor-␣, nuclear factor-kB (PϽ0.001), nitrotyrosine, and matrix metalloproteinase-9 (PϽ0.01), along with a lesser collagen content and IkB-␤ levels (PϽ0.001). Enhanced ubiquitin-proteasome activity in atherosclerotic lesions of patients with morning blood pressure surge is associated with inflammatory-dependent unstable plaque phenotype. These data suggest a potential interplay between morning blood pressure surge and ubiquitin-proteasome activity in atherosclerosis pathophysiology. (Hypertension. 2007;49:784-791.)Key Words: morning blood pressure Ⅲ atherosclerotic plaque Ⅲ inflammation Ⅲ ubiquitin-proteasome activity M any studies in the past decade have demonstrated diurnal variation in the onset of acute cardiovascular disorders in hypertensive patients, such as acute coronary syndrome, and ischemic and hemorrhagic stroke occurring in the morning (6:00 AM to noon), after a nadir in these events during the night. 1 Blood pressure (BP) falls during the night because of the reduction of sympathetic activity that is brought about by sleep and then increases steeply when in the morning the subject awakes and resumes his/her daily activities. 2 This increase occurs together with a peak incidence of cerebral and cardiac events in the morning hours. 3 Moreover, a recent prospective study suggests that higher morning BP surge (MBPS) might be an independent risk factor of atherosclerotic events beyond ambulatory BP and nocturnal BP falls. 4 The molecular mechanisms associating MBPS peak and vulnerable atherosclerotic plaque are not clear, although inflammation, which plays a central role in the cascade of events that result in plaque erosion and fissuring, also were related to MBPS. 5 There is emerging evidence that the ubiquitin-proteasome syste...

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown ( n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32–0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

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Two cases of infected false aneurysms of the subclavian artery in drug addicts are described. The clinical findings related to the location of these rare lesions are presented, together with an attempt to explain their pathophysiology. The signs and symptoms include a tender supraclavicular mass in an obviously septic patient associated with brachial plexus palsy, a swollen edematous arm, Horner's syndrome, and hemoptysis. Because of the complexity of symptoms, delay in diagnosis is common. It is emphasized that the recognition of this constellation of symptoms should prompt the physician to perform emergency angiography followed by immediate surgery.