Molecular Pathways in the Hypothalamus Lead to Hypertension and Cardiovascular Disease

A recent paper linked overexpression of mTORC1 (mammalian target of rapamycin complex 1) activity in the hypothalamus to the development of cardiovascular diseases.

MTORC1 is a serine/threonine protein kinase of the phosphatidylinositol 3-kinase (PI3K) protein family that regulates cell growth, proliferation, motility, survival, protein synthesis, and transcription. In cancer cells, the mTOR pathway is deregulated and signals tumor cells to grow, divide, and metastasize.

Investigators at the University of Iowa (Iowa City, USA) showed in the April 2, 2013, issue of the journal Cell Metabolism that mTOR signaling in the hypothalamus was tied to the activity of the sympathetic nervous system and to cardiovascular function.

Modulation of mTORC1 signaling caused dramatic changes in sympathetic traffic, blood flow, and arterial pressure. The data also demonstrated the importance of hypothalamic mTORC1 signaling in transducing the sympathetic and cardiovascular actions of leptin, a hormone produced by fat cells that has been implicated in obesity-related hypertension. Leptin activated mTORC1 in a specific part of the hypothalamus causing increased nerve activity and a rise in blood pressure. These effects were blocked by inhibiting activation of mTORC1.

"Our study shows that when this protein [mTORC1] is either activated or inhibited in a very specific manner, it can cause dramatic changes in blood pressure,” said senior author Dr. Kamal Rahmouni, associate professor of pharmacology and internal medicine at the University of Iowa. "Given the importance of this protein for the control of blood pressure, any abnormality in its activity might explain the hypertension associated with certain conditions like obesity and cardiovascular disease."

"Cardiovascular diseases are the leading cause of death worldwide, and hypertension is a major cardiovascular risk factor," said Dr. Rahmouni. "Our study identifies the protein called mTORC1 in the hypothalamus as a key player in the control of blood pressure. Targeting mTORC1 pathways may, therefore, be a promising strategy for the management of cardiovascular risk factors."

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