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With a focus on learning, we employ a range of strategies to support innovation, collaboration across centers, and university-wide discussion and decision-making

 

Fifteenth Annual Grant Winners 2014-2015

Title

Ang II Effects on MMP-9 and Collagen Levels in Hypertensive Rat Astrocytes

Dean

Lisa Deziel, Ph.D., Pharm.D. (HPD-PHR)
Linda Niessen, DMD, MPH, MPP (HPD-DEN)

Faculty and Students

Vudhya G. Yugandhar,  Ph.D. (HPD-PHR)
Michelle A. Clark, Ph.D. (HPD-PHR)
Umadevi Kandalam, Ph.D. (HPD-DEN)
Vanessa Matamoros (FAR)

Abstract

Hypertension (increased blood pressure) is a major health challenge worldwide because of its high frequency and concomitant increased risk of cardiovascular diseases, stroke and kidney diseases. The mechanisms responsible for the regulation of blood pressure (BP) are complex. One of the major effects observed in hypertension is thickening of vascular walls due to changes in the extracellular matrix (ECM). Collagen is a major component of the ECM and its levels are regulated by matrix metalloproteinases (MMPs). Among the 28 members of this family, MMP-9 and its tissue specific inhibitor 1 (TIMP-1) balance are important in maintaining ECM levels in capillaries. Imbalances in ECM levels due to collagen deposit can lead to tissue remodeling and an increase in BP. Angiotensin II (Ang II) is a biologically active octapeptide that mediates a plethora of effects including the control of BP. One mechanism by which Ang II induces vascular wall thickening in the periphery is by enhanced production of ECM proteins such as collagen. In the brain, astrocytes produce MMPs and collagen but the role of these proteins and their relationship with Ang II in the control of BP is unknown. We hypothesize that Ang II modulates MMP levels in astrocytes leading to an increase in collagen production. In a hypertensive state, there is dysregulation in MMP activities and collagen turnover that finally leads to collagen deposition in blood vessels. Increased collagen deposition in the brain may be a landmark event in hypertension. We will use astrocytes isolated from spontaneously hypertensive rats (SHR) and their normotensive controls to elucidate whether Ang II affects MMPs and collagen protein and gene levels. The Ang receptors involved in this effect will also be determined. Understanding the pathophysiology of Ang II- induced MMPs, and collagen levels will allow us to better prevent and treat hypertension.