Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a severe health problem worldwide, and vascular calcification (VC) contributes substantially to the cardiovascular morbidity and high mortality of CKD. CKD is often accompanied by a variety of pathophysiological states, such as inflammation, oxidative stress, hyperglycaemia, hyperparathyroidism and haemodynamic derangement, that can cause injuries to smooth muscle cells (SMCs) and endothelial cells (ECs) to promote VC. Similar to SMCs, whose role has been widely explored in VC, ECs may contribute to VC via osteochondral transdifferentiation, apoptosis, etc. In addition, given their location in the innermost layer of the blood vessel lumen and preferential reception of various pro-calcification stimuli, ECs can pass messages to vascular wall cells and communicate with them. Crosstalk between ECs and SMCs via cytokines through a paracrine mechanism, extracellular vesicles, miRNAs and myoendothelial gap junctions also plays a role in VC. In this review, we emphasize the role of intercellular crosstalk between ECs and SMCs in VC associated with CKD.

Keywords: CKD; crosstalk; endothelial cells; smooth muscle cells; vascular calcification.

FIGURE 1

Crosstalk between ECs and SMCs in CKD‐associated VC. From top to bottom, there are schematic diagrams of the lumen, vascular endothelial layer, elastic lamina, vascular smooth muscle cell layer and the outcomes of SMCs. The CKD milieu means a variety of stimulating factors with high levels of inflammation, oxidative stress, glucose, PTH, mechanical stress, etc. ECs and SMCs interact with each other through inflammation, MEGJ, vasodilator (eg NO), vasoconstrictor (eg ET‐1), pro‐calcification factor (eg BMP), MMPs, EVs and pro‐angiogenic and pro‐fibrotic growth factors (eg VEGF), etc. The blue arrowed line represents the effect of ECs on SMCs and the green arrowed line represents the effect of SMCs on ECs. Abbreviation: SMC, smooth muscle cell; EC, endothelial cell; IL, Interleukin; TNF‐α, tumor necrosis factor α; TGF‐β, transforming growth factor β; Pi, phosphate; IS, indoxyl sulphate; WBC, white blood cell; BP, blood pressure; Glu, glucose; RANKL, receptor activator of NFκ‐β ligand; OPN, osteopontin; MGP, matrix Gla protein; OPG, osteoprotegerin; BMP, bone morphogenetic protein; ET‐1, endothelin‐1; MEGJ, myoendothelial gap junctions; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; EDHF, endothelial‐derived hyperpolarizing factor; EVs, extracellular vesicles; MMP, matrix metalloproteinase; Runx2, runt‑related transcription factor2; MSX2, muscle segment homeobox 2; Cbfα1, core binding factor alpha 1; ALP, alkaline phosphatase; OC, osteocalcin; SA‑β‑gal, senescence‑associated β‑galactosidase; Mit dysfunction, mitochondrial dysfunction; VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; PDGF, platelet‐derived growth factor