Morning blood pressure surge as a destabilizing factor of atherosclerotic plaque: role of ubiquitin-proteasome activity.
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 (>70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T-lymphocytes, human leukocyte antigen-DR+cells, ubiquitin-proteasome activity, nuclear factor-kappaB, inhibitor kB-beta, tumor necrosis factor-alpha, 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-DR+cells (P<0.001), ubiquitin-proteasome activity, tumor necrosis factor-alpha, nuclear factor-kB (P<0.001), nitrotyrosine, and matrix metalloproteinase-9 (P<0.01), along with a lesser collagen content and IkB-beta levels (P<0.001). 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.
Marfella
Raffaele
R
Department of Geriatric and Metabolic Diseases, Second University of Naples, Naples, Italy. raffaele.marfella@unina2.it
Siniscalchi
Mario
M
Portoghese
Michele
M
Di Filippo
Clara
C
Ferraraccio
Franca
F
Schiattarella
Concetta
C
Crescenzi
Basilio
B
Sangiuolo
Paolo
P
Ferraro
Giuseppe
G
Siciliano
Silvio
S
Cinone
Francesca
F
Mazzarella
Gennaro
G
Martis
Simone
S
Verza
Mario
M
Coppola
Ludovico
L
Rossi
Francesco
F
D'Amico
Michele
M
Paolisso
Giuseppe
G
D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002340:Carotid Artery Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002940:Circadian Rhythm; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D002537:Intracranial Arteriosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D015854:Up-Regulation
D016328:NF-kappa B; D025801:Ubiquitin; C002744:3-nitrotyrosine; D014443:Tyrosine; D046988:Proteasome Endopeptidase Complex