My current research studies focus on biology and in vivo detection of matrix remodeling and calcification in cardiac valves and atherosclerotic plaques. Calcification is a characteristic feature of atherosclerosis and is predictive of cardiovascular events. Cardiovascular calcification has been viewed conventionally as a passive degenerative process. On the contrary, recent evidence suggests that calcification is a tightly regulated process of mineralization akin to bone formation. We reported previously that myofibroblast-like cells, due to their plasticity, respond to various stimuli by undergoing activation and sequential phenotypic differentiation. Moreover, accumulating data suggest that vascular and valvular myofibroblasts may acquire an osteoblastic phenotype and that pro-atherogenic stimuli may further promote expression of bone-regulating proteins, transcription factors, and eventually, calcification. However, the precise cellular and molecular mechanisms leading to ectopic calcification remain incompletely understood.

The inability to spatially and temporally resolve and quantify the dynamic pro-osteogenic molecular mechanisms in vivo also accounts for the limited knowledge in the field. By applying molecular imaging to calcifying vasculopathy and valvulopathy of apolipoproteinE-deficient (apoE-/-) mice, our resent imaging studies provide evidence that atherosclerotic inflammation precedes osteogenic activity and promotes calcification, explaining the epidemiological link between inflammation, hypercholesterolemia and calcification ( Circulation 2007;116: 2841-2850, Circulation 2007;116: 2782-2785, Circulation 2007;115: 377-386, Circulation 2007;115: 297-299) ). Development of therapies targeting aortic stenosis requires better understanding of molecular mechanisms of calcification that cause aortic and valvular dysfunction. Aortic valve stenosis is a common heart valve disease, but no therapy is currently available other then surgical valve replacement. Since atherosclerosis and aortic valve stenosis share similar mechanisms and epidemiological risk factors, our findings also apply to calcific aortic valve disease proposing that cellular-resolution molecular imaging can identify microcalcifications and subclinical valvular lesions, and potentially predict risk for devastating clinical complications in patients. Our results provide new insights regarding the biology of inflammation-triggered osteoblastic activity in early stages of atherosclerosis, and aid the exploration of novel, more refined therapeutic strategies to combat calcific cardiovascular disease.