Calcification in Atherosclerotic Plaque Vulnerability: Friend or Foe?

Abstract

Calcification is a clinical marker of atherosclerosis. This review focuses on recent findings on the association between calcification and plaque vulnerability. Calcified plaques have traditionally been regarded as stable atheromas, those causing stenosis may be more stable than non-calcified plaques. With the advances in intravascular imaging technology, the detection of the calcification and its surrounding plaque components have evolved. Microcalcifications and spotty calcifications represent an active stage of vascular calcification correlated with inflammation, whereas the degree of plaque calcification is strongly inversely related to macrophage infiltration. Asymptomatic patients have a higher content of plaque calcification than that in symptomatic patients. The effect of calcification might be biphasic. Plaque rupture has been shown to correlate positively with the number of spotty calcifications, and inversely with the number of large calcifications. There may be certain stages of calcium deposition that may be more atherogenic. Moreover, superficial calcifications are independently associated with plaque rupture and intraplaque hemorrhage, which may be due to the concentrated and asymmetrical distribution of biological stress in plaques. Conclusively, calcification of differential amounts, sizes, shapes, and positions may play differential roles in plaque homeostasis. The surrounding environments around the calcification within plaques also have impacts on plaque homeostasis. The interactive effects of these important factors of calcifications and plaques still await further study.

Ultrastructural Pathology of Atherosclerosis, Calcific Aortic Valve Disease, and Bioprosthetic Heart Valve Degeneration: Commonalities and Differences

“…The ultimate outcome of inflammation, mechanical stress, and intraplaque or intraleaflet haemorrhage is calcification [ 56 , 57 , 58 ], which has a variety of patterns considerably affecting the disease course [ 59 , 60 , 61 , 62 , 63 ]. The dystrophic calcification of degraded ECM components and biomineralisation mediated by the osteochondrogenic differentiation of mesenchymal cells are two different modalities of valve and plaque ossification [ 1 , 56 , 57 , 58 ].…”

A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE−/− Mice

“…Overall, our data suggest a divergent effect of E2 based on timing with the acceleration of calcification in actively-growing lesions. A higher prevalence of intraplaque hemorrhage and calcification in stroke patients indicates an association between increased calcification and plaque vulnerability [ 34 ]. Therefore, the acceleration of calcification in the actively-growing lesions by E2 thereby could potentially increase the risk of ischemic events.…”

“…The distribution of calcium within atherosclerotic lesions is also important in determining the susceptibility of the plaque to rupture and ensuing clinical consequences [ 34 ]. In advanced-lesions, calcification distribution was altered from a centralized deposition in the control-treated group to a more expansive even distribution along the length of the BCA in the E2-treated group, although without a change in overall calcified area or volume.…”

Intravascular Molecular Imaging: Near-Infrared Fluorescence as a New Frontier

“…Microcalcifications can be detected by OCT; however, OCT has difficulty in visualizing cellular-level calcifications. Also NIRF has the ability to visualize osteoblastic activity ( 63 ). Only a limited studies are available on the use of OsteoSense in vascular biology and plaque vulnerability ( 59 ).…”