Abstract P307: What A Difference Hypertension Makes: The Adventitia Hands Off To PVAT For Extracellular Matrix Remodeling As Blood Pressure Rises In The High Fat Fed Dahl SS Rat.

Abstract

Tunica media extracellular matrix remodeling is well understood to occur in response to elevation of blood pressure, considered a protective response. Remodeling of other tunicas is not well known. We have a long-term hypothesis that perivascular adipose tissue (PVAT) is responsive to hypertension and likely remodels to assist the blood vessel in protection against higher pressures. Here, we used the tunica adventitia and PVAT of the thoracic aorta in measuring extracellular matrix genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% fat) or high fat (HF; 60%) diet. These times were picked given relative increases mean arterial blood pressure (mm Hg) in the HF vs control (mmHg increase; 8 week: 14±5; 24 week = 35±8; p<0.05). The adventitia and PVAT were dissected apart, RNA isolated, cDNA synthesized and run on RT2 profiler array kits for ECM and Cell Adhesion genes. Differentially expressed genes (HF 2 fold > Con) were determined in Cytoscape, followed by identification of Hub Genes and construction of a Gene Regulatory network. At 8 weeks on HF diet, the adventitia had 29 upregulated genes (vs Con diet) while the PVAT had none. By contrast, at 24 weeks on diet, the HF adventitia had 3 upregulated genes while PVAT had 47. The top two genes elevated at 8 weeks in adventitia where thrombospondin 1 and collagen 8a1. Surprisingly, at 24 weeks, thrombospondin 1 was one of the three top genes upregulated in PVAT. The following transcription factors were identified as regulators of those genes upregulated in the 8 week adventitia: Adarb1, Fos, Gm10323, Smad3 and Mapk1 . By contrast, the key transcription factors for DEGS in the 24 week PVAT were Stat1, Bcl6B, Tsnax, Pax8, and Jun. Adarb1 (Adenosine deaminase RNA specific B1) was also determined to be a key regulator in PVAT remodeling. These data support that the PVAT responds biologically once blood pressure is elevated.