Identification of early pathological events in calcific aortic valve disease by molecular imaging

Abstract

The aberrant mineralization of soft tissues (i.e., ectopic calcification) recently has been associated with various chronic and degenerative conditions in humans. Cardiovascular tissue, particularly vasculature and valves, are among the peripheral tissues affected by the pathological deposition of calcium phosphate in connective tissue [1]. Although whether ectopic calcification originates from the same causes in different soft tissues is still unclear, the mineralization process seems to be triggered by chronic inflammatory conditions. This relationship has been especially demonstrated in the cardiovascular system, where macrophage infiltration and subsequent release of proteolytic enzymes and cytokines precedes the transformation of vascular smooth muscle cells and valve interstitial cells (VICs) into osteoblast-like cells. Over the last two decades, cardiovascular calcification has gradually gained the attention of more research groups with the acknowledgement that calcification constitutes an independent risk factor for cardiovascular morbidity and mortality [2-7]. Moreover, the prevalence of arterial calcification and calcific aortic valve disease (CAVD) is expected to increase, due to aging worldwide population. An estimated 2.1 million patients in Europe and 3.5 million patients in North America will suffer from severe CAVD by 2025 and 2050, respectively [8]. Therefore, a better understanding of the mechanisms underlying the initiation of CAVD will lead to the development of novel diagnostic and therapeutic methods to improve patients’ quality of life.