Objectives: Circulating HDL lipoprotein fraction is known to play an atheroprotective role by favouring macrophage cholesterol (C) efflux and by inhibiting LDL oxidation. We evaluated end-diet HDL plasma concentration and coronary atherogenesis outcome in high-cholesterol diet (HCD) treated pigs. Methods: Eighteen farm pigs were fed standard diet (CTRL) and HCD for 8 (HF) and for 16 weeks (HHF). Plasma total C and its fractions were measured on pre- and end-diet blood samples and ELISA for oxidized LDL (oxLDL) performed. Coronary arteries were segmented and serially cross-sectioned for intimal thickness (IT), intima to media thickness ratio (IMT) and lesion area (LA) morphometry (H&E and Weigert stains). Alpha-SM actin and CD107a antibodies were used for lesional VSMCs and macrophage-foam cells (MF-FCs) immunostaining respectively (% positive area). Number, grade and lesion morphometry together with VSMCs and macrophage-foam cells (MF-FC) concentration were assessed. Results: HF and HHF cases had comparable end-diet elevation of total C, LDL and oxLDL plasma values 10-fold respect to CTRL and HDL levels ranging from 20 to 80 mg/dl , inversely associated to lesion number and grade (0% to 50% type I to III and 33% to 75% type II to type IV lesions in HF and HHF segments respectively). HDL and C/HDL ratio values of HCD cases were directly and inversely related to corresponding mean IT, IMT and LA values (P<0.05). (Immuno)histology coronary profiling evidenced milder and more proximal lesions and intraplaque lower VSMCs/MF-FCs ratio at higher end-diet HDL level. Conclusion: These findings confirm the atheroprotective role of HDL in a HCD swine model of early coronary artery disease, leading to a reduced lesion grade and number and restricting atherogenesis to the proximal tract of arteries. The lower VSMCs/MF-FCs ratio at elevated HDL concentration suggests inhibition of VSMC activation as an additional mechanism of HDL-mediated protection.
HDL-MEDIATED ATHEROPROTECTION IN A HIGH CHOLESTEROL DIET SWINE MODEL BY QUANTITATIVE (IMMUNO)HISTOLOGY CORONARY PROFILING
Pelosi G;Puntoni M;Trivella M G;Parodi O
2014
Abstract
Objectives: Circulating HDL lipoprotein fraction is known to play an atheroprotective role by favouring macrophage cholesterol (C) efflux and by inhibiting LDL oxidation. We evaluated end-diet HDL plasma concentration and coronary atherogenesis outcome in high-cholesterol diet (HCD) treated pigs. Methods: Eighteen farm pigs were fed standard diet (CTRL) and HCD for 8 (HF) and for 16 weeks (HHF). Plasma total C and its fractions were measured on pre- and end-diet blood samples and ELISA for oxidized LDL (oxLDL) performed. Coronary arteries were segmented and serially cross-sectioned for intimal thickness (IT), intima to media thickness ratio (IMT) and lesion area (LA) morphometry (H&E and Weigert stains). Alpha-SM actin and CD107a antibodies were used for lesional VSMCs and macrophage-foam cells (MF-FCs) immunostaining respectively (% positive area). Number, grade and lesion morphometry together with VSMCs and macrophage-foam cells (MF-FC) concentration were assessed. Results: HF and HHF cases had comparable end-diet elevation of total C, LDL and oxLDL plasma values 10-fold respect to CTRL and HDL levels ranging from 20 to 80 mg/dl , inversely associated to lesion number and grade (0% to 50% type I to III and 33% to 75% type II to type IV lesions in HF and HHF segments respectively). HDL and C/HDL ratio values of HCD cases were directly and inversely related to corresponding mean IT, IMT and LA values (P<0.05). (Immuno)histology coronary profiling evidenced milder and more proximal lesions and intraplaque lower VSMCs/MF-FCs ratio at higher end-diet HDL level. Conclusion: These findings confirm the atheroprotective role of HDL in a HCD swine model of early coronary artery disease, leading to a reduced lesion grade and number and restricting atherogenesis to the proximal tract of arteries. The lower VSMCs/MF-FCs ratio at elevated HDL concentration suggests inhibition of VSMC activation as an additional mechanism of HDL-mediated protection.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
