Abstract 3442: Phosphorylated Heat Shock Protein 27 is Downregulated in Ascending Aortic Aneurysm associated with Bicuspid Aortic Valve
Background: Bicuspid aortic valves (BAV) are often associated with acquired lesions of the ascending aorta. Recent studies have demonstrated increased smooth muscle cell (SMC) apoptosis and decreased levels of matrix metalloproteinase (MMP)-9 and increased MMP-2 expression in BAV aortas compared to tricuspid aortic valve (TAV). We underwent proteomic analyses to reveal alterations at the protein level leading to aortic aneurysm in BAV.
Methods: Aortic wall segments were excized from 10 male patients undergoing ascending aortic aneurysm surgery. 5 patients had a BAV, 5 patients had a TAV. Median age was 58 (range 41– 68) years in BAV patients and 66 (52–73) in TAV (p=0.3). Histological examination excluded patients with arteriosclerosis and connective tissue disorder. Aortic samples were dissected, solubilized and 2-D gelelectrophoresis and mass-spectrometry performed.
Results: 2-D gel pattern analysis and mass-spectrometry revealed protein alterations in heat shock protein 27 (HSP 27) isoforms between BAV and TAV aortic samples. Among those HSP 27 isoform I was statistically significant downregulated in BAV compared to TAV specimen. Quantity of HSP 27 isoform I was median 2214 U (range 192– 6166) in BAV and 33081 U (6091–33247) in TAV aortas (p<0.01). Characterization of HSP 27 isoform I demonstrated that it differs from other HSP 27 isoforms by phosphorylation (see graphic).
Conclusions: Phosphorylated HSP27 is downregulated in BAV compared to TAV aortic aneurysm samples. This corresponds to a decreased stress resistance of BAV aortas, increased SMC apoptosis and differences in MMP-9 and MMP-2 expression compared to TAV samples.