Læknablaðið : fylgirit - 01.06.1982, Blaðsíða 11

PLENARY LECTURE
1
Atherosclerosis and the Cell Biology of the Arterial Wall
Gudmundur Thorgeirsson
University Hospitals of Cleveland, Cleveland, Ohio
In recent years atherosclerosis increasingly has been
regarded as a problem of the biology of arterial wall cells and
their interactions with blood cells and other blood components.
In spite of quantitative variations all established atheroscler-
otic lesions contain 3 major components: 1. Cells, mostly
smooth muscle cells (SMC), but also macrophages, especially in
early lesions. 2. Connective tissue proteins, collagen,
elastin and glycosaminoglycans (GAG). 3. Lipids, mostly
cholesteryl esters and free cholesterol.
The accumuiation of SMC in the intima has been assigned a
key role in ail current theories of atherogenesis. These cells
have the ability to synthesize all the connective tissue pro-
teins found in the lesions. In numerous animal models endothe-
lial injury (mechanical, chemical, immune mediated) results in
arterial lesions closely resembling spontaneous atherosclerosis
even in the absence of hyperl ipidemia. The discovery of a
specific protein in platelets that stimulates both proliferation
and directed migration of SMC (chemotaxis) provided foundation
for the current version of the endothelial injury hypothesis:
Endothelial injury-»Adherence of platelets and release of growth
and migratory stimulatory factor-»Mi gration of SMC from the
media to the intima+Proliferation of SMOProduction of connec-
tive tissue proteins. GAG and elastin have high affinity for
low density lipoproteins (LDL), possibly providing a link
between SMC prol iferation during early stages of atherosclerosis
and subsequent accumulation of extracellular lipids.
If release of platelet factors is a critical event in
atherogenesis, regulatory mechanisms that affect the inter-
action of platelets with the vascular wall are of major impor-
tance. The discovery of Thromboxane A2 (TXA2) in platelets
with potent proaggregatory and vasoconstricting effects, and
Prostacyclin (PGI) in endothelial cells with the opposite
actions provides for a powerful regulatory system. Imbalance
in this system such as decreased PGI2 production could promote
cell reactions in early atherosclerotic lesions as well as
thrombotic complications of advanced lesions.
The endothelial injury hypothesis proposes ce]l biolog-