Costimulatory and coinhibitory molecules of B7-CD28 family in cardiovascular atherosclerosis: A review

Abstract

Accumulating evidence supports the active involvement of vascular inflammation in atherosclerosis pathogenesis. Vascular inflammatory events within atherosclerotic plaques are predominated by innate antigen-presenting cells (APCs), including dendritic cells, macrophages, and adaptive immune cells such as T lymphocytes. The interaction between APCs and T cells is essential for the initiation and progression of vascular inflammation during atherosclerosis formation. B7-CD28 family members that provide either costimulatory or coinhibitory signals to T cells are important mediators of the cross-talk between APCs and T cells. The balance of different functional members of the B7-CD28 family shapes T cell responses during inflammation. Recent studies from both mouse and preclinical models have shown that targeting costimulatory molecules on APCs and T cells may be effective in treating vascular inflammatory diseases, especially atherosclerosis. In this review, we summarize recent advances in understanding how APC and T cells are involved in the pathogenesis of atherosclerosis by focusing on B7-CD28 family members and provide insight into the immunotherapeutic potential of targeting B7-CD28 family members in atherosclerosis. Abbreviations: APC = antigen presenting cell, ApoE = apolipoprotein E, BTLA = B and T lymphocyte attenuator, CTLA-4 = cytotoxic T lymphocyte antigen-4, DC = dendritic cell, ICOS/ICOSL = inducible costimulator and ligand, IFN-γ = interferongamma, IL = interleukin, ITIM = immunoreceptor tyrosine-based inhibitory, LDL = low-density lipoprotein, Ldlr = low-density lipoprotein receptor, MD-2 = myeloid differentiation-2, PD-1/PD-L1 = programmed death-1/programmed death-1 ligand, TLR = toll-like receptor, Treg = regulator T cell, TREM = triggering receptors expressed on myeloid cells.

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure

“…The obstruction of a coronary artery can happen quickly when, in response to a change in shear stress, lymphocytes adhere to the surface of the endothelial cells and, along with platelets, accumulate at the site and occlude the vessel. The endothelial cells become "sticky" when they express members of a family of immunoglobulin-like adhesion molecules that includes ICAM-1, ICAM-2, VCAM-1 and PECAM-1; this also aids in the transendothelial migration of the lymphocytes [30]. Melatonin has long been known to inhibit adhesion molecule expression on endothelial cells, which diminishes the likelihood of the occlusion of a coronary artery due to the buildup of lymphocytes [31,32] (Figure 1).…”