Cardiovascular risk factors regulate the expression of vascular endothelin receptors

Cardiovascular disease remains as the leading cause of death in the developed world. However, there is limited knowledge about how cardiovascular risk factors actually cause vascular disease. Traditional cardiovascular risk factors include increased circulating levels of low-density lipoproteins, cigarette smoking and hypertension (both strongly related to arterial wall injury), inflammation and atherosclerosis. The vascular endothelin receptors are a protein family that belongs to the larger family of G-protein coupled receptors. They mediate vascular smooth muscle contraction, proliferation and apoptosis, which are important events in the pathogenesis of atherosclerotic vascular disease. Recent investigations into intracellular signaling mechanisms suggest that the above risk factors increase the expression of endothelin receptors in vascular smooth muscle cells by activating intracellular mitogen-activated protein kinase pathways and downstream transcription factors such as nuclear factor-kappaB. Understanding the mechanisms involved in vascular endothelin receptor upregulation during cardiovascular disease may provide novel therapeutic approaches.