Diabetic conditions promote binding of monocytes to vascular smooth muscle cells and their subsequent differentiation

Li Meng, Jehyun Park, Qiangjun Cai, Linda Lanting, Marpadga A. Reddy, Rama Natarajan

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Diabetes is associated with significantly accelerated rates of atherosclerosis, key features of which include the presence of excessive macrophage-derived foam cells in the subendothelial space. We examined the hypothesis that enhanced monocyte-vascular smooth muscle cell (VSMC) interactions leading to subendothelial monocyte retention and differentiation to macrophages under diabetic conditions may be underlying mechanisms. Human aortic VSMCs (HVSMCs) treated with diabetic stimuli high glucose (HG) or S100B, a ligand of the receptor for advanced glycation end products, exhibited significantly increased binding of THP-1 monocytic cells. Diabetic stimuli increased the expression of the adhesive chemokine fractalkine (FKN) in HVSMCs. Pretreatment of HVSMCs with FKN or monocyte chemoattractant protein-1 (MCP-1) neutralizing antibodies significantly inhibited monocyte-VSMC binding, whereas monocytes treated with FKN showed enhanced binding to VSMC. Mouse aortic VSMCs (MVSMCs) derived from type 2 diabetic db/db mice exhibited significantly increased FKN levels and binding to mouse WEHI78/24 monocytic cells relative to nondiabetic control db/+ cells. The enhanced monocyte binding in db/db cells was abolished by both FKN and MCP-1 antibodies. Endothelium-denuded aortas from db/db mice and streptozotocininduced diabetic mice also exhibited enhanced FKN expression and monocyte binding, relative to respective controls. Coculture with HVSMCs increased CD36 expression in THP-1 cells, and this was significantly augmented by treatment of HVSMCs with S100B or HG. CD36 mRNA and protein levels were also significantly increased in WEHI78/24 cells after coincubation with db/db MVSMCs relative to control MVSMCs. These results demonstrate that diabetic conditions may accelerate atherosclerosis by inducing key chemokines in the vasculature that promote VSMC-monocyte interactions, subendothelial monocyte retention, and differentiation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Chemokine CX3CL1
Vascular Smooth Muscle
Smooth Muscle Myocytes
Monocytes
Chemokine CCL2
Chemokines
Cell Communication
Atherosclerosis
Macrophages
CD36 Antigens
Glucose
Foam Cells
Coculture Techniques
Neutralizing Antibodies
Adhesives
Endothelium
Aorta
Ligands
Messenger RNA
Antibodies

Keywords

  • Cell adhesion
  • Fractalkine
  • Macrophages
  • Monocyte chemoattractant protein-1
  • S100B

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Diabetic conditions promote binding of monocytes to vascular smooth muscle cells and their subsequent differentiation. / Meng, Li; Park, Jehyun; Cai, Qiangjun; Lanting, Linda; Reddy, Marpadga A.; Natarajan, Rama.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 298, No. 3, 03.2010.

Research output: Contribution to journalArticle

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