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People with high blood pressure have secondary hypertension, meaning that the root cause of the disease is known. In such cases, when the root cause is treated, blood pressure usually returns to normal or is significantly lowered. Hyperaldosteronism, a condition in which the adrenal glands produce too much aldosterone, is the most common cause of secondary hypertension.
Research, based on a genetic model identifies an unexpected layer in the regulation of adrenal gland development and in hyperaldosteronism.
The body’s adrenal glands produce a number of essential hormones, including aldosterone, which balances sodium and potassium in the blood. In hyperaldosteronism, the adrenal glands produce too much aldosterone, leading to low levels of potassium and increased sodium. Excess sodium leads to water retention, increasing the blood volume and blood pressure. The structure of the adrenal glands in mice lacking the Siah1 ubiquitin ligase gene was markedly different and they had increased levels of aldosterone.
Elevated levels of PIAS1, a Siah1 controlled protein is a key regulator of cholesterol biosynthesis,
Siah1 is a ubiquitin ligase that plays an important role in a number of cellular pathways, implicated in neurodegeneration and cancer. Patients that suffer from hyperaldosteronism exhibit mutations or epigenetic deregulation of the key pathway components, pointing to the relevance of our findings to humans and the justification for further exploration of this pathway for therapeutic purposes.
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