Remnant lipoproteins and atherogenesis.
Recent clinical studies have revealed that increased serum triglyceride (TG) levels are closely related to atherosclerosis, independently of serum levels of high-density lipoproteins (HDL) and low-density lipoproteins (LDL). Among triglyceride-rich lipoproteins (TRLs), remnant lipoproteins (RLPs) are considered to be atherogenic and an independent coronary risk factor. We previously reported that monocytes cultured in the presence of RLPs increased their adhesion to vascular endothelial cells. The underlying mechanism involved activation of RhoA, a member of small GTP binding proteins, resulting in activation of focal adhesion kinase (FAK) and s1-integrin. It is also known that RLPs enter vessel walls. In another study, we reported that RLPs induced smooth muscle cell (SMC) proliferation, independently of oxidative stress. Recently, we identified the molecular mechanisms, in which RLPs from hypertriglyceridemic patients stimulated SMC proliferation via epidermal growth factor (EGF) receptor transactivation and heparin-binding EGF-like growth factor (HB-EGF) shedding. More recently, we reported that apoB48 receptor was involved in RLP-induced foam cell formation in macrophages. The current review focused on the molecular mechanisms for the atherogenicity of RLPs.
Kawakami
Akio
A
Department of Geriatrics and Vascular Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima D809, Bunkyo-ku, Tokyo, Japan.
Yoshida
Masayuki
M
D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D015415:Biomarkers; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol