The impact of altered mechanobiology on aortic valve pathophysiology.

Calcific aortic valve disease (CAVD) is the most prevalent valvulopathy worldwide. Until recently, CAVD was viewed as a passive, degenerative process and an inevitable consequence of aging. Recent improvements in disease modeling, imaging, and analysis have greatly enhanced our understanding of CAVD. The aortic valve and its constituent cells are subjected to extreme changes in mechanical forces, so it follows that any changes in the underlying mechanobiology of the valve and its cells would have dire effects on function. Further, the mechanobiology of the aortic valve is intimately intertwined with numerous molecular pathways, with signal transduction between these aspects afforded by the dynamic plasma membrane. Changes to the plasma membrane itself, its regulation of the extracellular matrix, or the relay of signals into or out of the cell would negatively impact cell and tissue function. PURPOSE OF REVIEW: This review seeks to detail past and current published reports related to the mechanobiology of the aortic valve with a special emphasis on the implications of altered mechanobiology in the context of calcific aortic valve disease. RECENT FINDINGS: Investigations characterizing membrane composition and dynamics have provided new insights into the earliest stages of calcific aortic valve disease. Recent studies have suggested that the activation or suppression of key pathways contribute to disease progression but may also offer therapeutic targets. SUMMARY: This review highlights the critical involvement of mechanobiology and membrane dynamics in normal aortic valve physiology as well as valve pathology.

Synthesis of Water-Soluble Far-Red-Emitting Amphiphilic BODIPY Dyes.

We report the synthesis of two water-soluble BODIPY dyes with far-red absorption and near-infrared fluorescence following cell membrane insertion. Introduction of dicationic or dianionic groups imparts water solubility and prevents translocation of the dye through the plasma membrane for highly effective labeling. The dicationic form is particularly well localized to the plasma membrane and resists quenching even after >8 min of continuous light exposure. The dyes are almost completely nonemissive in water and other highly polar solvents, but display high-fluorescence yields in chloroform and upon insertion into the extracellular leaflet.