Matrix Vesicles as a Therapeutic Target for Vascular Calcification

Abstract

Vascular calcification (VC) is linked to an increased risk of heart disease, stroke, and atherosclerotic plaque rupture. It is a cell-active process regulated by vascular cells rather than pure passive calcium (Ca) deposition. In recent years, extracellular vesicles (EVs) have attracted extensive attention because of their essential role in the process of VC. Matrix vesicles (MVs), one type of EVs, are especially critical in extracellular matrix mineralization and the early stages of the development of VC. Vascular smooth muscle cells (VSMCs) have the potential to undergo phenotypic transformation and to serve as a nucleation site for hydroxyapatite crystals upon extracellular stimulation. However, it is not clear what underlying mechanism that MVs drive the VSMCs phenotype switching and to result in calcification. This article aims to review the detailed role of MVs in the progression of VC and compare the difference with other major drivers of calcification, including aging, uremia, mechanical stress, oxidative stress, and inflammation. We will also bring attention to the novel findings in the isolation and characterization of MVs, and the therapeutic application of MVs in VC.

Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells

“…AnxA6 involves the coordination of various physiological and pathological extracellular matrix (ECM) mineralization processes by regulating membrane and cytoskeleton organization, membrane trafficking, and signal transduction [ 18 ]. Growing evidence indicates that the abnormal expression of AnxA6 in osteoblasts and smooth muscle cells leads to some pathological processes such as the development of osteoporosis [ 19 ] and atherosclerosis [ 20 , 21 ]. The expression and distribution of annexins in cells are highly sensitive to changes in the mechanical microenvironment, especially fluid flow [ 14 ], whereas the role of AnxA6 in FSS-mediated osteogenic mineralization is unclear.…”

Coronary Artery Calcification: Current Concepts and Clinical Implications

“…The use of positron emission tomography fluorine imaging to identify high-risk plaques has shown promising results in terms of spatial resolution and accuracy in the detection of calcium deposits that are below the resolution of CT (200-500 µm). 18 F-NaF positron emission tomography-CT localized recently ruptured plaques and identified high-risk coronary lesions among patients with stable CAD. 70 Similarly, Doris et al 71 investigated the relationship between 18 F-NaF uptake and coronary calcification progression in stable CAD and identified 18 F-NaF as a marker of future progression, able to identify patients and coronary segments with rapid progression.…”

Endoplasmic Reticulum Stress and Pathogenesis of Vascular Calcification

“…That is, high Ca 2+ and Pi concentrations can promote the expression of BMP2, Runx2, MSX2, and osteocalcin in VSMCs, thus promoting osteogenic-like differentiation of VSMCs. In addition, imbalanced Ca 2+ and Pi concentrations can cause accumulation of Ca 2+ in VSMCs, thereby promoting the release and mineralization of matrix vesicles as well as the apoptosis of VSMCs ( 24 , 25 ). However, despite the abundance of research on the various risk factors for VC, including hyperphosphatemia, hypercalcemia, oxidative stress, inflammation, and apoptosis, there is a dearth of information regarding the associated regulatory pathways and molecules.…”