Molecular Imaging Insights Into Early Inflammatory Stages of Arterial and Aortic Valve Calcification

Abstract

Traditional imaging modalities such as computed tomography, although perfectly adept at identifying and quantifying advanced calcification, cannot detect the early stages of this disorder and offer limited insight into the mechanisms of mineral dysregulation. This review presents optical molecular imaging as a promising tool that simultaneously detects pathobiological processes associated with inflammation and early stages of calcification in vivo at the (sub)cellular levels. Research into treatment of cardiovascular calcification is lacking, as shown by clinical trials that have failed to demonstrate the reduction of calcific aortic stenosis. Hence the need to elucidate the pathways that contribute to cardiovascular calcification and to develop new therapeutic strategies to prevent or reverse calcification has driven investigations into the use of molecular imaging. This review discusses studies that have used molecular imaging methods to advance knowledge of cardiovascular calcification, focusing in particular on the inflammation-dependent mechanisms of arterial and aortic valve calcification.

Ideal Cardiovascular Health and the Prevalence and Severity of Aortic Stenosis in Elderly Patients

“…Beyond risk of cardiovascular disease, worse CVHS has been associated with higher circulating levels of biomarkers of inflammation, endothelial dysfunction, and neurohormonal activation,18, 36, 37, 38, 39 pathways that have also been implicated in the development and progression of AV sclerosis and calcification 8, 40, 41. Lipoproteins and inflammatory cells, such as macrophages and T cells,42 have been identified in early AV lesions,43 and inflammatory activity, visualized by positron emission tomography imaging, has been documented in patients with even mild stenosis 44.…”

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

“…Importantly, it is well recognized that coagulation factors play a significant role in the process of inflammation and atherosclerosis 25. The attenuation of protein C has been reported to reduce anti‐apoptotic activity of the endothelial barrier and to promote local inflammation within the arterial wall,25 which is accompanied, at least to a certain degree, by calcification 26. In addition, infiltration of vascular tissue is characterized by increased oxidative stress and subsequently by endothelial dysfunction leading to increased vascular stiffness 27.…”

Progression of coronary artery calcification at the crossroads: sign of progression or stabilization of coronary atherosclerosis?

“…Both ex vivo and intravascular ultrasound (IVUS) studies have shown that CAC is closely related to atherosclerotic plaque burden, although the molecular basis of this process remains uncertain (15)(16)(17). Recent molecular imaging studies support the current notion that vascular calcification is not a passive degenerative process, but actually an active process that leads to ectopic mineralization promoted by the expression of multiple pro-osteogenic cytokines, transcription factors, and mineralization-regulating proteins by macrophages and other inflammatory cells (18). In this regard, fluorescence molecular multimodality imaging has shown potential to provide insightful data concerning arterial osteogenesis at much earlier stages of atherosclerosis (19,20).…”

“…Regarding future alternative therapeutic approaches, the combined application of molecular imaging agents with anticalcification drugs such as bisphosphonate might potentially enable targeting at different stages of the disease (18).…”