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Endothelium and atherosclerosis
L Badimon1, J J Badimon, W Penny
1Division of Cardiology, Mount Sinai Medical Center, New York, New York.
Insights
Damaged endothelium impairs vascular regulation, leading to vasoconstriction and increased risk of arterial thrombosis and atherosclerosis. An intact endothelium is crucial for preventing these conditions.
Area of Science:
- Cardiovascular Science
- Vascular Biology
- Pathophysiology
Background:
- Atherosclerosis is a complex disease influenced by lipids, blood pressure, and thrombogenic factors.
- Endothelial dysfunction is closely linked to atherosclerosis initiation.
- Normal endothelium regulates vascular tone and prevents thrombosis.
Purpose of the Study:
- To review the effect of damaged endothelium on atherosclerotic disease development.
- To investigate the role of endothelial integrity in vascular health.
Main Methods:
- Studied endothelium-dependent coronary vasoreactivity in pigs after balloon angioplasty.
- Administered intracoronary acetylcholine before and after balloon injury.
- Assessed changes in left anterior descending artery diameter.
Main Results:
- Superficial balloon injury significantly altered endothelium-dependent vasoreactivity.
- Acetylcholine caused dose-dependent vasoconstriction after balloon angioplasty.
- Vasoconstriction can increase arterial wall-shear forces and platelet deposition.
Conclusions:
- The intact endothelium provides significant protection against arterial thrombosis.
- A healthy endothelium is vital in preventing atherosclerosis and vasoconstriction.
Purpose:
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.
Methods And 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.
Conclusion:
The intact endothelium is one of the greatest sources of protection from arterial thrombosis, atherosclerosis and vasoconstriction.