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(Circulation. 1997;95:5-7.)
© 1997 American Heart Association, Inc.

Articles

Atherogenic Lipids, Vascular Dysfunction, and Clinical Signs of Ischemic Heart Disease

Andrew P. Selwyn, MD; Scott Kinlay, MB, BS, PhD; Peter Libby, MD; Peter Ganz, MD

Harvard Medical School, Cardiovascular Division, Brigham and Women's Hospital, Boston, Mass.

Correspondence to Andrew P. Selwyn, MD, Professor of Medicine, Harvard Medical School, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.

Key Words: Editorials • lipids • ischemia

	Introduction

 
The report by Tamai and colleagues¹ in this issue demonstrates that therapeutic lowering of serum cholesterol, LDL, and oxidized LDL results in improvement in endothelium-dependent dilation in the forearm vasculature of patients with hypercholesterolemia. These observations are novel and particularly interesting because they show that atherogenic lipids can interact with and adversely affect blood vessel function even more rapidly than previously suspected. It is important to consider that past research² has focused on the effects of serum lipids on atherogenesis over decades. However, more recent trials in patients have shown that treatment of serum lipids can improve clinical outcomes in 18 months to 3 years,^{3 4} improve endothelial dysfunction in atherosclerotic arteries in 6 to 12 months,^{5 6 7} and affect endothelium-dependent vasomotor function in the forearm in 2 to 12 weeks.⁸ The article by Tamai et al¹ now shows that the relationship between atherogenic lipids and vascular dysfunction is dynamic and subject to change within minutes. This finding has important implications regarding the pathogenesis of ischemic syndromes and the use of potent and rapidly acting lipid-lowering therapies in patients.

	Experimental Effects of LDL on Cell/Vessel Wall Function

 
Native LDL has little direct effect on essential function(s) in cells within the arterial wall. However, when LDL is metabolized by endothelial cells, the normal component antioxidants (eg, -tocopherols and ß-carotene) are exhausted, the polyunsaturated phospholipids are converted to reactive hydroxyfatty acids, lysophosphotidylcholine is formed, and the proteins in the apolipoprotein-B 100 moiety undergo covalent modification and fragmentation so that the ligand can no longer bind to the classic LDL receptor. Eventually, this . . . [Full Text of this Article]

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