Linda L. Demer, MD, PhD and Yin Tintut, PhD
LDemer@mednet.ucla.edu / 310-206-267
YTintut@mednet.ucla.edu / 310-206-9964
Demer-Tintut Cardiovascular Biomineralization Laboratory
Our laboratory is addressing the problems of coronary calcification and aortic stenosis, with a focus on the mechanism by which calcium mineral forms inside cardiovascular tissues and atherosclerotic plaque. This field began with our discovery that the process is regulated at the molecular level and that multipotent vascular stem cells produce calcium mineral by the same processes driving embryonic skeletal osteogenesis. We are characterizing these cells with respect to multilineage capacity, transdifferentiation to osteoblastic cells, and hydroxyapatite nanocrystal formation. One particularly interesting finding is that, in culture, these cells self-organize into intricate patterns that we can predict and control using computational analysis and reaction-diffusion principles. Another, relevant to tissue engineering, is left-right chirality, a preference for rightward orientation and alignment when they migrate across micromachined matrix interfaces. Our robust in vitro and mouse models of vascular calcification are assayed by several quantitative techniques including live, fused PET-CT imaging, computer-controlled biomechanical testing, and atomic force and second-harmonic generation microscopy. We are also testing effects of hyperlipidemia, exercise, and lipid-lowering agents on vascular and valvular calcification. These findings have major clinical implications given the widespread recommendations for use of vitamin D, calcium, exercise, bone-anabolic agents, and cholesterol-lowering drugs.
