Division of Valvular and Coronary Disease, Department of Cardiology, Karolinska University Hospital, 141 86 Stockholm, Sweden.
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Cardiovasc Res. 2021 Jul 27;117(9):2016-2029. doi: 10.1093/cvr/cvab038.
Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, ageing, 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.
动脉壁和瓣膜的钙化是周围动脉粥样硬化和冠状动脉粥样硬化、主动脉瓣狭窄、衰老、糖尿病和慢性肾病的病理生理过程的重要组成部分。本综述旨在更好地了解细胞外磷酸盐及其在细胞外基质上作为磷酸钙保留的能力如何引发动脉和瓣膜的矿化过程。在这种情况下，骨骼矿化的生理过程仍然是病理性软组织矿化的人体模型。可溶性（离子化）钙沉淀发生在细胞外磷酸盐上；无机或暴露的有机磷酸盐上均可发生。有机磷酸盐分为结构性（磷脂、核酸）或能量性（对应于磷酸转移活性）。细胞外磷酸盐促使血管平滑肌和瓣膜间质细胞向成骨细胞基因表达模式发生表型转变，从而引发矿化的活跃阶段。一系列防御系统可保护动脉和瓣膜组织钙化。鉴于磷酸盐在软组织钙化中的主要作用，磷酸盐类似物和/或防止磷酸盐耗散代表了动脉和瓣膜钙化的潜在新型治疗方法。
