From organic and inorganic phosphates to valvular and vascular calcifications

Abstract

Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, aging, diabetes, and chronic kidney disease. This review aims to better understand how extracellular phosphates and their ability to be retained as calcium phosphates on the extracellular matrix initiate the mineralization process of arteries and valves. In this context, the physiological process of bone mineralization remains a human model for pathological soft tissue mineralization. Soluble (ionized) calcium precipitation occurs on extracellular phosphates; either with inorganic or on exposed organic phosphates. Organic phosphates are classified as either structural (phospholipids, nucleic acids) or energetic (corresponding to phosphoryl transfer activities). Extracellular phosphates promote a phenotypic shift in vascular smooth muscle and valvular interstitial cells towards an osteoblast gene expression pattern, which provokes the active phase of mineralization. A line of defense systems protects arterial and valvular tissue calcifications. Given the major roles of phosphate in soft tissue calcification, phosphate mimetics and/or prevention of phosphate dissipation represent novel potential therapeutic approaches for arterial and valvular calcification.

Associations of Social Vulnerability Index With Pathologic Myocardial Findings at Autopsy

“…For instance, Fibroblast Growth Factor 23 (FGF23), a key mediator of salt homeostasis shown to be elevated in high SVI communities and among individuals with high inorganic phosphate intake, has been established as a driver of myocardial fibrosis ( 18 , 19 ). These phosphates may further disturb salt homeostasis, directly trigger pro-fibrotic fibroblast activation ( 20 , 21 ), exacerbating vascular calcification ( 22 ). Epidemiologically, neighborhoods with better access to food resources in urban settings have lower premature CVD mortality ( 23 ), these healthy food sources tend to be less available for Black populations, and low availability of healthy foods is associated with a lower quality diet ( 24 , 25 ).…”

Fatty acids and aortic valve stenosis

“…Inflammatory mediators give rise to a disturbance in the balance of synthesis and degradation of extracellular matrix (ECM) [23]. Malfunctioning ECM and matrix vesicles play a role in the initial stage of calcification acting as foundation for dystrophic microcalcification [24,25]. In response to inflammatory stimuli, valvular interstitial cells express osteogenic genes like bone morphogenic protein 2 (BMP2), Runx2 in addition to intracellular adhesion molecule 1 (ICAM-1) which also suggest a tight link between inflammation and calcification [26].…”

Generation of mRNA Vaccine: An Analysis of Two Types of Vectors

“…During the biosynthesis of nucleic acids and proteins, large amounts of phosphates may be produced as by-products, disrupting the completion of these essential physiological reactions. Phosphatases are critical in regulating and reducing the cellular concentration of these phosphates [43][44][45][46]. During the generation of IVT mRNA, the phosphatase treatment could be necessary for regulating the excess of phosphorothioate, phosphorothiolate, imidiphosphate, and boranophosphate that may be produced from the use of chemically modified cap analogs [2].…”