Increased monocyte-platelet aggregates and monocyte-endothelial adhesion in healthy individuals with vitamin D deficiency

• Published in: The FASEB journal Vol. 34; no. 8; p. 11133
• Main Authors: Tay, Hui Min, Yeap, Wei Hseun, Dalan, Rinkoo, Wong, Siew Cheng, Hou, Han Wei
• Format: Journal Article
• Language: English
• Published: United States 01.08.2020
• Subjects: Atherosclerosis - metabolism; Atherosclerosis - pathology; Blood Platelets - metabolism; Blood Platelets - physiology; Cell Adhesion - physiology; Cells, Cultured; Dietary Supplements; Down-Regulation - physiology; Endothelial Cells - metabolism; Endothelial Cells - physiology; Female; Healthy Volunteers; Human Umbilical Vein Endothelial Cells; Humans; Inflammation - metabolism; Inflammation - pathology; Male; Monocytes - metabolism; Monocytes - physiology; Platelet Activation - physiology; Receptors, Calcitriol - metabolism; Vitamin D - metabolism; Vitamin D Deficiency - metabolism; Vitamin D Deficiency - physiopathology; atherosclerosis; monocytes; microfluidics; vitamin D
• ISSN: 1530-6860
• DOI: 10.1096/fj.202000822R

Vitamin D deficiency is a major public health problem worldwide, linked to several chronic diseases including cardiovascular diseases. While immunomodulatory effects of vitamin D on monocytes have been reported in cardiovascular and metabolic diseases, there is limited understanding on monocyte phenotype in healthy individuals with suboptimal vitamin D levels and without any clinical diseases. In this work, we performed label-free, microfluidic isolation of monocytes, and characterized their functional phenotype using flow cytometry and in vitro vascular models in healthy subjects with (n = 7) and without vitamin D deficiency (n = 16). Vitamin D deficient (VitD-Def) subjects (25(OH)D level < 26 ng/mL) expressed significant downregulation of vitamin D receptor (VDR) on monocytes as compared to controls (P < .0001), and VDR expression was well-associated with serum 25(OH)D levels. Increased monocyte-platelet aggregates (MPA), a marker for platelet activation, were also observed in VitD-Def subjects (P < .05) which suggests a pro-inflammatory monocyte phenotype. Monocyte adhesion to endothelial cells, an early-stage atherosclerosis event, was also higher in VitD-Def individuals, and inversely correlated to serum 25(OH)D level (P < .05). Taken together, these results indicate the pro-inflammatory state and atherogenic potential of monocytes in VitD-Def healthy subjects, and propound the use of vitamin D supplementation as a prospective immunomodulatory and anti-inflammatory therapy in atherosclerosis.