The extracellular matrix of degenerated tricuspid aortic valves exhibited a 6.5-fold enrichment of Annexin A3 compared to bicuspid aortic valves, suggesting distinct aetiologies.
Observational (n=88)
No
Proteomic analysis of the extracellular matrix in degenerated aortic valves reveals distinct molecular profiles between bicuspid and tricuspid valves, suggesting different underlying etiologies.
Effect estimate: FC 6.5
p-value: p=1.1 x 10^-16
Abstract Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1. 1 × 10 –16 and the fold change 6. 5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (humanₐvdₑcm. surgsci. uu. se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.
Beusch et al. (Sat,) conducted a observational in Aortic valve degeneration (n=88). Tricuspid aortic valve (TAV) vs. Bicuspid aortic valve (BAV) was evaluated on Annexin A3 abundance in extracellular matrix (FC 6.5, p=1.1 x 10^-16). The extracellular matrix of degenerated tricuspid aortic valves exhibited a 6.5-fold enrichment of Annexin A3 compared to bicuspid aortic valves, suggesting distinct aetiologies.