Small dense LDL and VLDL predict common carotid artery IMT and elicit an inflammatory response in peripheral blood mononuclear and endothelial cells.
OBJECTIVE
The presence of small dense LDL has been associated with increased cardiovascular risk and with the progression of coronary and carotid atherosclerosis in case-control and prospective studies. The aim of this study was to investigate the relation between different lipoprotein subfractions with intima-media thickness of the common carotid artery in a free-living, healthy population, and to evaluate whether in patients with comparable LDL-C, the different lipoprotein subclasses differently affected the expression of chemokines, cytokines and adhesion molecules in peripheral blood mononuclear and endothelial cells.


RESULTS
The lipoprotein cholesterol profile and the LDL buoyancy (LDL-RF) were evaluated in a cohort of 156 healthy subjects randomly selected from the PLIC (Progressione Lesione Intimale Carotidea) study. The LDL-RF was directly and significantly correlated to weight, body mass index, waist, hip, waist/hip ratio, triglycerides, fasting glycemia and intima media thickness (IMT) of the common carotid artery and inversely related to HDL-C. After multivariate statistical analysis, IMT was independently associated with age, LDL-RF and HDL-C and among the lipoprotein subclasses, only those corresponding to triglyceride-rich lipoproteins (TGRL) and small dense LDL (sdLDL) independently predicted IMT variance. Peripheral blood mononuclear cells (PBMC) isolated from patients with the predominance of sdLDL (pattern B) had an increased mRNA expression of pro-inflammatory molecules compared to PBMC from patients with the predominance of large LDL (pattern A); in endothelial cells TGRL from pattern B subjects and much less those from pattern A induced the expression of pro-inflammatory genes while sdLDL from either pattern A or B subjects were less effective and showed comparable effects.


CONCLUSIONS
LDL-relative flotation rate significantly correlates with several cardiometabolic parameters. Furthermore cholesterol levels lipoprotein subfractions within the TGRL and sdLDL density range are independent predictors of IMT variance and are associated with a pro-inflammatory activation of PBMC and endothelial cells.
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. Danilo.Norata@unimi.it
Giuseppe Danilo
GD
Norata
Sara
S
Raselli
Liliana
L
Grigore
Katia
K
Garlaschelli
Daniela
D
Vianello
Sandra
S
Bertocco
Alberto
A
Zambon
Alberico Luigi
AL
Catapano
D015992:Body Mass Index; D017536:Carotid Artery, Common / Q000648:ultrastructure*; D002784:Cholesterol; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood*; D015331:Cohort Studies; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000648:ultrastructure*; D017540:Tunica Media / Q000648:ultrastructure*; D020298:U937 Cells
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D018836:Inflammation Mediators; D008074:Lipoproteins; D014280:Triglycerides; C030104:lipoprotein cholesterol; C030087:lipoprotein triglyceride; D002784:Cholesterol