Lipids and endothelium-dependent vasodilation--a review.
Studies using both in vitro and in vivo techniques have repeatedly shown that endothelium-dependent vasodilation (EDV) is impaired in different forms of experimental as well as human hypercholesterolemia. Clearly this impaired EDV can be reversed by lowering cholesterol levels by diet or medical therapy. Competitive blocking of L-arginine, changes in nitric oxide synthase activity, increased release of endothelin-1, and inactivation of nitric oxide due to superoxide ions all contribute to the impairment in EDV during dyslipidemia. The oxidation of low density lipoprotein, with its compound lysophosphatidylcholine, plays a critical role in these events. However, data on the role of triglycerides and fat-rich meals regarding EDV are not so consistent as data for cholesterol, although a view that the compositions of individual fatty acids and antioxidants are of major importance is emerging. Thus, this review shows that while impaired EDV is a general feature of hypercholesterolemia, the mechanisms involved and the therapeutic opportunities available still have to be investigated. Furthermore, discrepancies regarding the role of triglycerides and fat content in food may be explained by divergent effects of different fatty acids on the endothelium.
Lind
Lars
L
Department of Medicine, Uppsala University Hospital and AstraZeneca R&D, Möndal, Sweden. lars.lind@medsci.uu.se
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology; D066298:In Vitro Techniques; D008055:Lipids / Q000502:physiology*; D008074:Lipoproteins / Q000494:pharmacology; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000502:physiology; D014280:Triglycerides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000924:Anticholesteremic Agents; D005227:Fatty Acids; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D009569:Nitric Oxide