Vascular Calcification… It’s Complicated

The Vascular Discovery meeting in San Francisco last week was whirlwind of learning and networking. My favorite moment was at the Friday 7 am Early Career Training session where, by coincidence, I ended up at the same table with @Ritu_Ganguly1, @MoradiShayan and @JeffHsuMD. We had all signed up to provide social media coverage of the conference via the Twitter account of the Journal of the American Heart Association (JAHA), so it was great to meet them in person. Later in the day, Ritu and I worked (read: laughed and cried) through the Genome Editing Bootcamp together, a challenging case-based workshop led by the excellent Dr. Kiran Musunuru.

As discussed in my pre-conference blog, vascular research is extremely pertinent to chronic kidney disease. Children on dialysis can manifest the same arterial calcification as a 70 year old. An established mechanism in vascular calcification is the phenotype switch where vascular smooth muscle cells start behaving like bone cells, secreting matrix vesicles filled with calcium-phosphate mineral into the extracellular matrix. At the Vascular Discovery meeting Dr. Elena Aikawa discussed advances made in the understanding of matrix vesicles, which are critical precursors of microcalcifications. In a JCI paper, her group reported co-localization of the protein sortilin with caveolin-1 and tissue nonspecific alkaline phosphatase, and defined sortilin’s role in loading mineral into vesicles. Dr. Aikawa raised a follow up question: Would future therapies that block activation of sortilin prevent microcalcifications, and thus prevent vascular calcification?

Dr. Catherine Shanahan, who described the role of programmed cell death or apoptosis in dialysis-associated vascular calcification, discussed the interaction of aging and vascular cell phenotype change at her Vascular Discovery talk. Her lab has been examining the nuclear lamina, or network of filament proteins which are a part of the cell nucleus. It turns out that the aging vascular smooth muscle cell accumulates prelamin A (see Circulation Research paper), which leads to DNA damage and triggers the osteogenic phenotype switch. This raises the intriguing question: Can we reverse cell aging to block vascular calcification?

The nature of scientific research is that more questions are raised as progress is made. Scientific meetings such as Vascular Discovery have an important role in updating investigators and clinicians, fostering new collaborations and training early career professionals.

Wei Ling Lau Headshot

Wei Ling Lau, MD is Assistant Professor in Nephrology at University of California-Irvine. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology. Follow her on Twitter @Kidneys1st

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