WnT SIGNALING IN ATHEROSCLEROSIS: THE OSTEOCARDIOLOGY GO/ NO GO THEORY



Nalini M. Rajamannan, M.D., Mayo Clinic, Rochester, MN, USA

Recent epidemiological studies have revealed the risk factors associated for vascular atherosclerosis, including male gender, smoking, hypertension and elevated serum cholesterol, are similar to the risk factors associated with development of calcific aortic valve disease (CAVD), calcific aortic disease (CAD) and coronary artery calcification (CAC). The results of the experimental and clinical studies demonstrate that traditional risk factors initiate early atherosclerosis which over time differentiates to form bone in the heart causing, clinical CAVD, CAD, and CAC. It is critical to understand the cellular mechanisms of cardiovascular calcification, the end stage process of the atherosclerosis, to define the critical time point to modify this cellular process before it is too late. Experimental models suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of disease. To date, randomized clinical trials in this field have not demonstrated medical therapy can slow progression. Therefore, ongoing studies are necessary to translate cellular biology to turn basic science into future clinical success. This review will summarize the role of Wnt Signaling in osteocardiology to unravel the dilemma of the proper timing of therapy- the Go/ No Go timepoint to slow progression of cardiovascular calcification.