Abstract
Objectives
Recent studies have shown that shear stress can alter the integrity and gene expression of the aortic wall. We aim to analyze the link between jet dynamic, histological alterations, and gene expression patterns of the proximal aorta in patients with aortic valve disease.
Methods
We prospectively identified a total of 139 consecutive patients who were referred for aortic valve replacement (AVR) from January 2012 through December 2015. All patients underwent pre-operative MRI assessment to determine the maximal shear stress area of the proximal aorta. Depending of the aorta diameter we subdivided our study population in three subgroup (i.e., patients with a diameter ≤40mm, 41–49mm and ≥50mm). Based on the MRI results, two aortic wall tissue samples were collected during surgery. One sample were acquired from an area of low wall shear stress (WSS) and the second from the area of maximal WSS. The samples were graded in seven histopathologic features.
For RNA isolation the tissue was disrupted using a Tissue Lyser II (Qiagen). For the gene expression analysis of h18S, hCCL2, hCOL1A1, hVCAM1, and hELN reverse transcription of RNA was carried out using the High-capacity cDNA kit (life-technologies,USA). Therefore, 125 ng total RNA from tissue samples were reversely transcribed into cDNA.
Results
Regardless of the aortic valve functional lesion (i.e., stenosis or regurgitation), the maximal area of WSS was in the major curvature of the proximal aorta (73%, n=102). We observed that in both tissue samples just the orientation of vascular smooth muscle cell was strongly related to the diameter of the ascending aorta (p=0.004 vs. p=0.0032). In the whole study population any significant correlation was found between maximal cross-sectional aortic diameter and genes expression. However, in the subgroup analysis we identified that the tissue samples who were exposed to higher wall shear stress and presented a diameter ≥50mm, showed a statically significant gene over-expresion of COL1A1 (p=0.041) and ELN (p=0.01). In the tissue samples with a low WSS we also identified a significant over-expression of CCL2 (p=0.005) and COL1A1 (p=0.01).
Conclusions
Tissue samples from the slow WSS area with a proximal aortic diameter ≥50mm presented elevated levels of inflammatory response genes (i.e, CCL2). On the other hand, samples that were exposed to higher WSS demonstrated more relation to changes in the architecture of the connective fibres (i.e., elastin and collagen).
Acknowledgement/Funding
None
Linkage Analysis of Transvalvular Flow Patterns, Histopathology, and Target Gene Expression in Aortic Valve Disease