title: Pulse-pressure-driven neutral lipid accumulation and correlative proinflammatory markers of accelerated atherogenesis.
abstract: In athero-prone areas of the human aorta, an accumulation of neutral lipids in the arterial intima precedes the arrival of monocytes and the initiation of the fatty streak. This study continues the investigation of a similar preinflammatory process in the coronary arteries of the sodium-sensitive hypertensive Dahl S rat, focusing on the hemodynamic forces associated with the neutral lipid influx and on concurrent changes in serum levels of certain proinflammatory markers. Animals were conditioned from weaning on a high-saturated fat, high-cholesterol diet until early adolescence (age 12 weeks), at which point dietary sodium was increased, and changes in blood pressure, serum analytes and histologic markers were tracked. The first half of the 12-day induction period was characterized by an immediate rise in pulse pressure that persisted above baseline. Serum levels of free monomeric C-reactive protein (mCRP) (as monomer/dimer ratio by Western blot densitometry) rose concurrently with pulse pressure and preceded the influx of neutral lipid into the arterial intima. Levels of oxidized LDL-cholesterol (oxLDL) closely tracked that of neutral lipid accumulation. In this model, elevated pulse pressure appears to drive the activation of circulating CRP and the influx of neutral lipids into the arterial intima, which leads to increased oxLDL levels.
authors.affiliation: Department of Hospital Laboratories, UMass Memorial Medical Center, One Biotech Park, Suite 200, 365 Plantation Street, Worcester, MA 01605-2376, USA. kieferc@ummhc.org
authors.forename: Charles R
authors.initials: CR
authors.lastname: Kiefer
authors.forename: James B
authors.initials: JB
authors.lastname: McKenney
authors.forename: Jane F
authors.initials: JF
authors.lastname: Trainor
authors.forename: L Michael
authors.initials: LM
authors.lastname: Snyder
mesh_terms: D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002097:C-Reactive Protein / Q000032:analysis*; D002791:Cholesterol, Dietary / Q000633:toxicity; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004036:Diet, Atherogenic; D004039:Diet, Sodium-Restricted; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000633:toxicity; D012995:Solubility; D017539:Tunica Intima / Q000378:metabolism*; D014657:Vasculitis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D012982:Sodium, Dietary; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein