Læknablaðið : fylgirit - 01.06.1982, Page 12

ical mechanisms to explain the association between known risk
factors and atherosclerosis: Hypertension, hypercholesterol-
emia and smoking directly affect endothel.ial integrity; diabetes
and smoking affect PGI2 production; insulin and LDL promote
SMC-proliferation; diabetes and aging affect the compliance of
vascular wall collagen and elastin and predispose the vessel
wall to endothelial injury.
Direct observations of endothelial denudation are limited.
More subtle functional and biochemical alterations may be
caused by the initiating atherogenic factors and still result
in increased endothelial permeability. Hemodynamic shearing,
hypercholesterolemia and experimental diabetes, in addition to
increasing endothelial permeabi1ity, all have been shown to
enhance histamine forming capacity in arterial walls. Recent
work in our laboratory has demonstrated that isolated endothe-
lial cells have the capacity to synthesize histamine. Histamine
production may serve a coupling role between endothelial injury
and altered endothelial permeability.
The endothelial injury hypothesis does not explain the
accumulation of lipids inside intimal SMC. Lysosomes contain
cholesteryl esterase. Since free cholesterol is cleared from
cells ten times faster than cholesterolesters lysosomes may
have an important function in the dynamic balance between
inflow and production on one hand and utilization and outflow
on the other. Even subtle changes in this balance over many
years may result in grave consequences. The first intracellu-
lar lipid accumulation that takes place during experimental
atherosclerosis occurs within lysosomes. Lysosomal activity is
decreased in diabetes and increased in hypertension and hyper-
cholesteroiemia, but perhaps not sufficiently to meet the
burden of markedly increased lipid inflow.
Summary: Atherosclerosis is a complex celiular reaction
that involves endothelium, SMC, circulating platelets and
monocytes, lysosomes, connective tissue proteins, lipoproteins
and lipoprotein receptors.