Title:The Role of the Endothelium in the Pathogenesis of Atherosclerosis and its Therapeutic Implications
Volume: 12
Issue: 4
Author(s): Marc J. George, Rajesh Kharbanda and Raymond J. MacAllister
Affiliation:
Keywords:
Atherosclerosis, endothelin, endothelium, endothelial dysfunction, inflammation, myocardial ischaemia, myocardial
infarction, nitric oxide, novel therapies, progenitor cells, prostacyclin, thromboxane.
Abstract: Atherosclerosis is the major cause of morbidity and mortality worldwide. Endothelial dysfunction is central to
the pathogenesis of atherosclerosis, initiating a triad of lipid accumulation in the vessel wall, a co-existent inflammatory
response and proliferation of smooth muscle cells. It has also been implicated in the precipitation of acute ischaemia, and
the determination of the extent of injury following such complications.
Healthy endothelium regulates numerous blood vessel functions, including vascular tone, cell adhesiveness, and coagulation
through the production of mediators. The best characterised of these are the vasodilators, nitric oxide (NO), prostacyclin,
and endothelium derived hyperpolarising factor, and the vasoconstrictors thromboxane and endothelin. The endothelium
itself may also be maintained by bone-marrow derived endothelial progenitor cells (EPC) which are mobilised in response
to vascular injury and have angiogenic and proliferative properties.
Understanding of the biology of the endothelium in atherosclerosis has led to new treatments and more may follow. Work
is ongoing into NO bioavailability, prostacyclin agonists, endothelin and thromboxane antagonists, novel antiinflammatory
and anti-oxidative agents as well as means of harnessing the properties of EPCs. It is hoped that this research
will yield clinically useful approaches that will retard the progression of atherosclerosis and reduce the incidence or
consequences of acute complications.
