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Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression
G Nickenig1, O Jung, K Strehlow
1Klinik III für Innere Medizin, Universität zu Köln, Cologne, Germany.
The American Journal of Physiology
|June 1, 1997
Summary
High cholesterol levels increase angiotensin II type 1 (AT1) receptor expression and function in rabbit aortas. This suggests a link between hypercholesterolemia and vascular diseases like hypertension.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Lipid Metabolism
Background:
- Low-density lipoprotein (LDL) is known to increase angiotensin II type 1 (AT1) receptor gene expression in vascular smooth muscle cells.
- Elevated serum cholesterol levels may influence AT1 receptor function and expression in vivo.
Purpose of the Study:
- To investigate whether elevated cholesterol upregulates AT1 receptor expression and its functional response to angiotensin II in vivo.
- To compare the vasoconstrictive effects and AT1 receptor expression in normocholesterolemic and hypercholesterolemic rabbits.
Main Methods:
- Vascular contraction experiments on isolated aortic rings.
- Radioligand binding assays to assess cell surface AT1 receptor density.
- Northern blot analysis to measure AT1-receptor mRNA levels.
Main Results:
- Hypercholesterolemic rabbits exhibited increased angiotensin II-induced vasoconstriction compared to normocholesterolemic rabbits.
- A twofold increase in cell surface AT1 receptor density was observed in hypercholesterolemic rabbits.
- Steady-state levels of AT1-receptor mRNA were elevated by approximately 220% in hypercholesterolemic rabbit aortas.
Conclusions:
- Hypercholesterolemia is associated with the upregulation of both expression and function of vascular AT1 receptors in vivo.
- This suggests a potential mechanism linking hypercholesterolemia to chronic vascular diseases such as hypertension and arteriosclerosis.
- Further confirmation in humans is warranted to validate these findings.