Cardiovascular Calcification and its Interrelationships with Skeletal Bone

Friday, January 19, 2018 -
2:00pm to 3:00pm
The FUNG Auditorium
Linda Demer

Professor of Medicine (Cardiology), Physiology and Bioengineering

Executive Director, Specialty Training and Advanced Research (STAR) Program

Executive Vice Chair, Department of Medicine

UC Los Angeles

 

Cardiovascular Calcification and its Interrelationships with Skeletal Bone

Abstract: 
Dr. Demer helped pioneer the field of vascular calcification research by showing that the process is actively regulated and occurs through bone formation by vascular cells that differentiate into bone cells, in a process that recapitulates embryonic osteogenesis.  The process is now known to be induced by a variety of mechanisms, including inflammatory cytokines, oxidized lipoproteins, vitamin D, bone morphogenetic protein, and kidney disease.  The vascular cells that become osteoblasts were isolated and found to have stem cell properties with multilineage potential. In culture, these cells self-organize into intricate, periodic patterns that are predictable by a computational simulation based on a mathematical model of the principle of reaction-diffusion (a system of partial differential equations whose parameters depend on relative rates of diffusion of two molecular morphogens involving positive and negative feedback loops).  The morphogens were identified and also found in human plaque, and model predictions were confirmed experimentally.  Possibly explaining the self-organization, a novel left-right chirality was observed in the vascular stem cells:  they turn right in response to a micro-machined matrix interface and align at a specific orientation, forming macropatterns.  Micromachined surfaces can coax the cells to recapitulate vascular patterns, such as those in spider angiomas and organ tissues. With respect to clinical implications, controversy continues to rage over whether calcification mechanically stabilizes or destabilizes plaque.  Compliance mismatch and finite element modeling suggest destabilizing effects at surfaces facing the direction of stress, but the literature is rich in conflicting results, and some have argued that a microscopic calcium deposit causes greater instability than a large deposit.  The recent demonstration that statins promote coronary calcification has fueled the flames. 
Bio: 

Dr. Linda Demer obtained her BS in mathematics and chemistry at the University of Arizona and completed the MD-PhD program at Johns Hopkins, with her graduate work in biomedical engineering studying the anisotropic biaxial mechanical properties of myocardium under Frank Yin (who, it so happens, did his graduate work at UC San Diego, under the mentorship of Y.C. Fung).  She also studied ventricular mechanics using pressure-volume loops with Suga and Sagawa, before doing her clinical training in internal medicine at Baylor.  While there, she invented a device for monitoring real-time mechanical changes in coronary plaque during balloon angioplasty in patients, using pressure-volume loops.  During cardiology fellowship, she studied in vivo coronary flow reserve and myocardial perfusion reserve, with Lance Gould, using digital angiography in animal models and PET scanning in humans.

As a faculty member at UCLA, in medicine, physiology and bioengineering, she pioneered the field of cardiovascular calcification research by showing that the phenomenon is actively regulated by vascular stem cells.  She served as Chief of Cardiology and now serves as Professor and Vice Chair of Medicine.  She also directs the UCLA STAR Program, which provides PhD training for physicians at the level of subspecialty fellowship.  She serves on the Editorial Boards for Circulation Research, Circulation, and Arteriosclerosis, Thrombosis, and Vascular Biology.  She received the Jeffrey Hoeg Award from the American Heart Association, co-chaired the Gordon Research Conference on Atherosclerosis, and served as President of the North American Vascular Biology Organization and as a charter member of an NIH study section.