M. Corsten (1,2), H. Heymer (1,2), E. Männer (1,2), L. Xianghai (1,3), T. Bozoglu (3), N. Klymiuk (1,2), A. Baehr (1,2), C. Kupatt (1,3)

1. Department of Internal Medicine I, Klinikum rechts der Isar, TU Munich, Germany; 2. Center for Innovative Medical Models; LMU Munich, Germany; 3 TUM Klinikum Deutsches Herzzentrum, TU Munich, Germany

Background/Introduction

Cardiac pressure overload causes left ventricular remodelling with pathological hypertrophy by inducing a chronic burden on the left ventricle (LV). To identify potential therapy targets and better understand the pathophysiology of the disease, a pig model was established in which luminal narrowing resembling aortic stenosis is achieved by stent placement in the descending aorta using a catheter-based technique.

Methods

In a catheter-based intervention a stent is placed in the descending aorta that gradually reduces the aortic lumen to about 40%. Hemodynamic measurements proximal and distal to the stent and LV angiography were performed at baseline and after eight weeks. Sirius red staining on systematically sampled pieces of LV indicate the level of fibrosis. Further, expression of hypertrophy-related genes, particularly genes involved in fibrotic remodelling, such as COL1A2, COL3A1 and extra-cellular-matrix regulators, is determined using a comprehensive panel of qPCRs comprising 13 target genes.

Results and conclusion

A significantly higher amount of collagen was detected in stented pigs compared to controls (stented: 17.16% of LV [n=5] vs. control: 8.87% of LV [n=8], p= 0,0003). Thus, the model effectively mimics progressive pressure overload and its effects on left ventricular remodelling, providing a valuable foundation for studying cardiac hypertrophy. qPCR analysis of hypertrophy-related genes is ongoing and will provide a potential therapeutic target.