Morning Blood Pressure Surge as a Destabilizing Factor of Atherosclerotic Plaque

Abstract

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...

Ethnic Differences in the Degree of Morning Blood Pressure Surge and in Its Determinants Between Japanese and European Hypertensive Subjects

“…On the background of our previous report that excessive sleep-trough MS was an independent predictor of stroke in elderly Japanese hypertensive patients, 10 the present data are relevant to the interpretation of recent studies, which assessed the association between MS and target organ damage or cardiovascular events through the analysis of international databases, including subjects with different ethnic background, 11,[25][26][27] sometimes reaching discrepant conclusions. For example, recently, in The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, sleep-trough MS was not found to be a significant risk factor for cardiovascular events.…”

Proteasome Activity as a Target of Hormone Replacement Therapy–Dependent Plaque Stabilization in Postmenopausal Women

“…We reported previously that oxidative stress-dependent UPS overactivity contributes to the clinical instability of atherosclerotic plaques in hypertensive, 15 diabetic, 16 and symptomatic patients 17 by promoting plaque rupture induced by NF-B-dependent inflammation. Now, in the present report, we provide evidence for the critical involvement of UPS in the process of plaque stabilization realized by HRT in postmenopausal women.…”

Prognostic Value of the Morning Blood Pressure Surge in 5645 Subjects From 8 Populations

“…Indeed, an exaggerated pressure load leads to fracture of the elastin fibers, to disorganization and hypertrophy of the muscular layers of the arterial wall, 28 and to plaque rupture. 29 These mechanisms might be particularly active in atherosclerotic arteries, 28 in the presence of oxidative stress, 29,30 or in older subjects with impaired baroreflexes. 31 …”