title: Macromolecular transport in the arterial intima: comparison of chronic and acute injuries.
abstract: Hypertension is a known risk factor for the development of atherosclerosis, which is characterized by the abnormal accumulation of low-density lipoprotein and other plasma-borne macromolecules. The goal of this study was to measure accumulation of a plasma-borne macromolecular marker, horseradish peroxidase (HRP; 44 kDa), in the aortic intima and media of chronically hypertensive rats. HRP transport in 2-yr-old spontaneously hypertensive rats (SHR) was compared with that in age-matched Wistar-Kyoto rats (WKY) under conditions in which blood pressures were not significantly different during the 15-min HRP circulation. Intimal accumulation and medial HRP concentration profiles were obtained from methacrylate-embedded sections after reaction with 3,3'-diaminobenzidine and H2O2. Data were analyzed using a mathematical model of macromolecular transport to quantify the permeabilities of endothelium and internal elastic lamina (IEL). Chronic hypertension increased endothelial permeability without a change in IEL permeability. An apparent convective flux of HRP into the intima of SHR raised intimal HRP to a concentration higher than that of HRP in the plasma. Our results suggest that the intimal accumulation of plasma-borne macromolecules from pressure-driven convection is normally minimized by an intact endothelium. Similar changes resulted from acute injury by lipopolysaccharide, suggesting endothelial injury could account for transport changes associated with hypertension. After either chronic or acute endothelial damage, transport of macromolecules into the intima increases, but the IEL continues to retard transport of macromolecules beyond the intima, resulting in increased intimal accumulation.
authors.affiliation: Department of Cell Biology, Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Penn
authors.forename: S
authors.initials: S
authors.lastname: Rangaswamy
authors.forename: G M
authors.initials: GM
authors.lastname: Saidel
authors.forename: G M
authors.initials: GM
authors.lastname: Chisolm
mesh_terms: D000818:Animals; D001011:Aorta / Q000293:injuries / Q000502:physiology / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000453:epidemiology / Q000503:physiopathology*; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D006973:Hypertension / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012485:Salmonella typhi; D017539:Tunica Intima / Q000293:injuries* / Q000502:physiology / Q000503:physiopathology*; D017540:Tunica Media / Q000502:physiology / Q000503:physiopathology*
chemical_list: D008070:Lipopolysaccharides; D006735:Horseradish Peroxidase