Abstract 5869: Aortic Valve Stenosis Progression Parallels Changes in Extracellular Matrix Gene Expression and Angiogenesis
Aortic valve disease is the most frequent native valve disease in Europe, and the third most frequent cause of cardiovascular death. The biological mechanisms underlying aortic valve degeneration, ultimately resulting in calcific aortic stenosis show similarities to atherosclerosis. We investigated extracellular matrix (ECM) molecules and angiogenesis as important components of atherosclerosis in aortic stenosis. Aortic leaflets from valve replacement surgeries and heart transplants were collected in the operating room after a careful echocardiographic validation of mean valve gradients (mvg) within 7 days of surgery. RNA expression profiles of healthy (control), as well as sclerotic (mvg=6±2mmHg, mean±SD), mildly (mvg=22±12mmHg), moderately (mvg=49±16mmHg) and severely stenotic (mvg=63±15mmHg) aortic valve leaflets (n=5 per group) were analyzed using an Affymetrix Human Gene 1.0 ST Array. Genes with an absolute fold change of ±2.0 in at least 4 samples per group were selected for further analysis. Collagen types I, III, V, XIV, XV and XXI as well as cathepsin S, B, D and K and perlecan showed a valve gradient-dependent increase of expression. Expressions of collagens type Ia1, Ia2, IIIa1 and Va1 and cathepsins S and D showed a significant correlation with stenosis progression (14,5 (9–17) m/sec/year, median-(range), p<0,05). The antiangiogenic ECM molecule chondromodulin was at a low level across the spectrum of mvgs, while VEGF decreased in parallel to increasing mvg. The data demonstrate an increase in ECM and suppression of angiogenesis in direct correlation with mvg and aortic stenosis progression.