Vascular Calcification—New Insights into Its Mechanism

Abstract

Vascular calcification (VC), which is categorized by intimal and medial calcification, depending on the site(s) involved within the vessel, is closely related to cardiovascular disease. Specifically, medial calcification is prevalent in certain medical situations, including chronic kidney disease and diabetes. The past few decades have seen extensive research into VC, revealing that the mechanism of VC is not merely a consequence of a high-phosphorous and -calcium milieu, but also occurs via delicate and well-organized biologic processes, including an imbalance between osteochondrogenic signaling and anticalcific events. In addition to traditionally established osteogenic signaling, dysfunctional calcium homeostasis is prerequisite in the development of VC. Moreover, loss of defensive mechanisms, by microorganelle dysfunction, including hyper-fragmented mitochondria, mitochondrial oxidative stress, defective autophagy or mitophagy, and endoplasmic reticulum (ER) stress, may all contribute to VC. To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, we provide this review of a detailed updated molecular mechanism of VC. This encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.

Effects of Eicosapentaenoic Acid on Arterial Calcification

“…Additionally, complex mechanisms are common in both intimal calcification and medial calcification. The mechanism included failed anti-calcification processes due to loss of calcification inhibitors including osteoprotegerin, osteopontin, matrix Gla protein (MGP), fetuin-A and pyrophosphate [48,[70][71][72][73], induction of osteo/chondroblast-like cells producing extracellular vesicles [74], cell death resulting in release of apoptotic bodies or necrotic debris that cause nucleation of apatite [75], calcium/phosphate dysregulation causing deposits calcium phosphate hydroxyapatite [76], nucleation complexes formed during bone remodeling, and matrix degradation/modification [77].…”

Caloric Intake in Renal Patients: Repercussions on Mineral Metabolism

“…VC refers to mineral deposition in the vascular system, in the form of Ca-P complexes [ 116 ]. Although VC is part of the normal aging process, some diseases such as diabetes, hypertension, and CKD can accelerate this process [ 116 , 117 , 118 ]. Vascular and other soft-tissue calcifications are a major problem in end-stage CKD.…”

“…In CKD patients, medial artery calcification is the most prevalent form of VC and is associated with increased stiffness of the artery wall [ 119 ]. VC is one of the major contributors to cardiovascular mortality in these patients [ 116 , 118 ].…”

The Preventive Effects of Xanthohumol on Vascular Calcification Induced by Vitamin D3 Plus Nicotine

“…Accumulating studies have demonstrated that VC is highly regulated by biological processes involving the transformation from the VSMC’s phenotype into osteoblast-like cells. VC is characterized by decreased expression of contractile proteins including smooth muscle 22 alpha (SM22α) and alpha-smooth muscle actin (α-SMA) [ 2 ], and increased expression of bone-related proteins such as runt-related transcription factor 2 (Runx2) [ 3 ] and bone morphogenetic protein 2 (BMP-2) [ 4 ].…”