Role of the Brain Renin Angiotensin System in Neuroinflammation

Investigating the role of RAS in neuroinflammation to understand hypertension

Full Project Name:Role of the Brain Renin Angiotensin System in NeuroinflammationPrincipal Investigator:Pablo Nakagawa, PhD, PhysiologyAward Amount:$500,000

Award Date

February2022

Project Duration:48 months

Project Description Narrative:

High blood pressure is often called the “silent killer” because there are not noticeable symptoms, but elevated blood pressure can lead to heart disease, stroke, and other consequences like dementia and arterial disease. Currently, heart disease and strokes remain the no. 1 and no. 5 killers in Wisconsin: affecting 82,735 Wisconsin residents in 2016 alone. It is expected that the hypertension crisis will worsen because elevated blood pressure is one of the key features of human aging.

There are mainly two types of cells in the brain: neuron and glial cells. These cells work in the renin angiotensin system (RAS) of the brain. While RAS is one of the most studied mechanisms of blood control, there is a certain glial cell that has been indicated as a contributor to the development of hypertension and obesity that has not been studied. This specific glial cell, microglial, is the resident immune cell in the brain. Through this award, investigators strive to understand the involvement of RAS and microglia cells that contribute to hypertension. Project partners aim to discover new targets and therapeutic tools that will help combat high blood pressure in patients.

Outcomes & Lessons Learned:

Concluded that the prorenin receptor is involved in multiple cellular processes, including regulation of the brain RAS and neuroinflammation, based on the project studies, which has the opportunity to contribute to the development of therapies for salt-sensitive hypertension, a prevalent condition among the 50% of Wisconsin's population over 50 that has hypertension
Resulted in three publications and three national and international presentations
Continuing to breed mouse models to test hypotheses related to signaling suppression of the inflammatory response in the brain
Leveraged over $230,000 from the American Heart Association

Project Updates:

Acquired key materials to conduct the proposed project experiments, including transgenic animals, and began breeding to expand the colony and achieve conditional control of gene expression
Validating the genetic constructs designed to be studied in cell culture experiments