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Sphingolipids in essential hypertension and endothelial dysfunction
Spijkers, L.J.A.
Publication date
2013
Link to publication
Citation for published version (APA):
Spijkers, L. J. A. (2013). Sphingolipids in essential hypertension and endothelial dysfunction.
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Aim of the study
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Aim
From the previous two chapters it becomes clear that sphingolipids play an important role in the regulation of endothelial function, but also that many questions regarding sphingolipids and vascular function are still unanswered. One of the main questions that we will address in the next chapters is how sphingolipids are involved in regulation of endothelial function under the pathological circumstances of hypertension.
In the next chapters we will investigate how hypertension, as described in the first chapter as a disease state associated with endothelial dysfunction, affects vascular sphingolipid metabolism and biology. An important related question is whether this has functional consequences. In other words; do possible alterations of sphingolipid metabolism in hypertension contribute to increased vasomotor tone or elevated blood pressure (BP) (chapters 3, 4 and 6)? If so, this may have two important consequences. Firstly, this implicates that modulation of sphingolipid metabolism is a potential pharmacological target to decrease BP and/or improve vascular function (chapter 6). Secondly, this may represent a possible mechanism by which drugs that affect sphingolipid metabolism, for instance an immune system modulatory drug (chapter 5), impair vascular function and increase BP.
We have previously shown that the potent vasoconstrictor angiotensin II is a modulator of endothelial sphingolipid metabolism. Here we will address the question whether this is similar for the endothelium-derived contracting factor endothelin-1 and whether this phenomenon is altered in hypertension (chapter 7). In addition, since sphingolipids are involved in the regulation of endothelial function, we examined whether sphingolipids are involved in the release of endothelium-borne Weibel-Palade bodies, which store endothelin-1, but predominantly store von Willebrand Factor (chapter 8).
Overall, the outlined research in this thesis will shed a light on the role of sphingolipids in the regulation of vascular function in hypertension.
