Endothelium and atherosclerosis.
OBJECTIVE
To review the effect of damaged endothelium on the development of atherosclerotic disease.


BACKGROUND
Atherosclerotic cardiovascular disease is a complex problem involving lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance and thrombogenic factors. The loss of functional, if not structural, integrity of the vascular endothelium is closely related to the initiation of atherosclerosis. The endothelium contributes to local vascular regulation. Normal endothelial cells are thrombo-resistant; they prevent leukocyte adhesion and control vascular tone by converting angiotensin I into angiotensin II, inactivating bradykinin, norepinephrine, serotonin and ADP, and by secreting vasodilator substances, such as prostacyclin and endothelium-derived relaxing factor (EDRF), and contracting factors such as endothelin. Endothelin is a potent vasoconstrictor peptide that increases intracellular calcium, causing a rapid and transient increase in c-fos and c-myc messenger (m)RNA levels and DNA synthesis in rat vascular smooth muscle cells. In isolated vessel segments, altered endothelial vasoreactivity is usually demonstrated following mechanical trauma to the endothelium.


RESULTS
We investigated the function of normal and damaged endothelium in pigs, following superficial balloon injury, which produces a significant alteration in endothelium-dependent coronary vasoreactivity. The anesthetized pigs were given an intracoronary (left anterior descending artery) infusion of acetylcholine. The balloon injury caused a local transient spasm while the distal uninjured vessel did not change. When acetylcholine was given before the balloon injury, the diameter of the left anterior descending artery did not change, even after preconstriction in vivo with prostaglandin (PG) F2 alpha, but acetylcholine given after the balloon angioplasty caused dose-dependent vasoconstriction. It is known that vasoconstriction in arteries can reduce blood flow and increase arterial wall-shear forces, which increase platelet deposition in injured arteries and may precipitate rupture of atherosclerotic plaques.


CONCLUSIONS
The intact endothelium is one of the greatest sources of protection from arterial thrombosis, atherosclerosis and vasoconstriction.
Badimon
L
L
Division of Cardiology, Mount Sinai Medical Center, New York, New York.
Badimon
J J
JJ
Penny
W
W
Webster
M W
MW
Chesebro
J H
JH
Fuster
V
V
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000109:Acetylcholine; D001920:Bradykinin