Biomolecules Orchestrating Cardiovascular Calcification

Abstract

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies.

Flexible 3-D Electrochemical Impedance Spectroscopy Sensors Incorporating Phase Delay for Comprehensive Characterization of Atherosclerosis

“…We also observed a strong negative correlation between 18 F-NaF and SMC infiltration into the intima, likely due to their known transdifferentiation into an osteochondrogenic-like cell type that contributes to vascular calcification. [26][27][28][29][30] Indeed, there is a strong correlation between 18 F-NaF signal, cardiovascular risk factors, and culprit lesions leading to myocardial infarction. 7 PET imaging, despite its versatility and clinical applicability, suffers from certain drawbacks, primarily its limited spatial resolution and reliance on radiotracers.…”

Periostin Augments Vascular Smooth Muscle Cell Calcification via β-Catenin Signaling

“…The uremic environment with hyperphosphatemia induces a pro-inflammatory state, which is considered to be a key mechanism for accelerated calcification in CKD [ 2 ]. Multiple inflammatory mediators have been linked to the pro-calcific environment in CKD [ 2 , 4 , 36 ]. Periostin has been connected with vascular and renal inflammatory processes [ 15 , 21 , 22 , 24 ] and, therefore, may be an important aspect in the complex signaling pathways of vascular calcification.…”

“…The development of pro-calcific VSMCs is orchestrated by complex signaling pathways [ 3 ]. A variety of pro-inflammatory signaling molecules have been shown to modulate pro-calcific pathways in VSMCs and augment their calcification [ 4 ]. Interference with pro-inflammatory mediators may prevent the development of vascular calcification [ 5 ].…”

Scaffold-free human vascular calcification model using a bio-three-dimensional printer

“…In biological calcified arteriosclerosis, expression of osteogenic genes is upregulated, and the SMC phenotype changes to osteoblast-like cells [26]. Aging, inflammation, oxidative stress, hyperphosphatemia, and oxidized low-density lipoprotein (LDL)-stimulated arteries can induce runt-related transcription factor 2 (RUNX2) and Msh homeobox 2 (MSX2) osteogenic transition of vascular SMC [27,28]. These transcription factors induce the expression of the bone morphogenic protein (BMP) and that of other transcription factors, resulting in vascular calcification.…”