Human vascular smooth muscle cells possess functional CCR5

Area of Science:

• Immunology
• Cardiovascular Biology
• Cell Biology

Background:

• CC chemokine receptors modulate inflammation, primarily on leukocytes.
• Emerging evidence suggests vascular smooth muscle cells (VSMCs) respond to CC chemokines.
• CCR5, a CC chemokine receptor, is known as a co-receptor for HIV.

Purpose of the Study:

• To investigate the expression and function of CCR5 in human arterial smooth muscle cells.
• To determine if macrophage inflammatory protein-1beta (MIP-1beta) acts as an agonist for CCR5 in VSMCs.
• To explore the downstream effects of MIP-1beta signaling on tissue factor activity in VSMCs.

Main Methods:

• RNA blot hybridization and reverse transcription-polymerase chain reaction (RT-PCR) to detect CCR5 mRNA in human aortic and coronary artery VSMCs.
• Immunohistochemistry to identify CCR5 and MIP-1beta in atherosclerotic plaques.
• In vitro studies using VSMC cultures to measure intracellular calcium changes and tissue factor activity in response to MIP-1beta.

Main Results:

• Human aortic and coronary artery smooth muscle cells express CCR5 mRNA.
• CCR5 and MIP-1beta were detected in VSMCs and macrophages within atherosclerotic plaques.
• MIP-1beta stimulation of VSMCs led to increased intracellular calcium and tissue factor activity, effects blocked by anti-CCR5 antibodies.

Conclusions:

• Human arterial smooth muscle cells express functional CCR5 receptors.
• MIP-1beta acts as an agonist for CCR5 on human arterial smooth muscle cells.
• CCR5 signaling in VSMCs may contribute to arterial thrombosis through increased tissue factor activity.