Immunologic Markers Associated with Periphral Arterial Disease
Atherosclerosis, is a pathological remodelling of the arteries which is a major cause of morbidity and mortality in developed countries; this pathology is the underlying basis of myocardial infarction, stroke and peripheral artery disease.
Atherosclerosis can be considered as an unusual form of chronic inflammation occurring within the artery wall. A number of data support the pathogenetic role of inflammation in the etiology of atherosclerosis; inflammation is an immunologic phenomenon. One of the most convincing evidences of this statement stems form the observation that fatty streaks, the earliest detectable lesions in atherosclerosis, contain macrophage-derived foamy cells that derive from circulating monocytes; CD4 T lymphocytes are also present in the atherosclerotic plaques.
The Rolling. Adhesion, and Infiltration of immune cells (monocytes and CD4 T lymphocytes) that circulate in the peripheral blood within the endotelium is regulated by two major families of proteins expressed on the surface of immune cells and on the surface of endothelial cells: selectins and integrins. Chemokines or chemoattractant cytokines are also extremely important in the control of cell trafficking and for the recruitment of immune cells in inflammatory sites. Some chemokines that can act as potent mediators of monocyte migration and macrophage differentiation are expressed in human atherosclerotic lesions. In particular, macrophage chemoattractant protein 1 (MCP-1) and its specific receptor CCR2 are strongly believed to be involved in the in the initial stages of atherogenesis. Additonal support to the patogenetic role of inflammation in the development of athersoclerotic plaques stems from the observation that different cytokines preferentially trigger the development of atherosclerotic plaques (e.g. TH1-like cytokines are “bad cytokines” within this biologic scenario). This becomes clearer when one considers that TH1 cytokines are prototipic inflammatory cytokines. Cytokines and other immunological proteins present in the atherosclerotic lesions are not only produced by CD4 T lymphocytes; infact, fibroblast growth factors (FGFs) and platelet-derived growth factor (PDGF) are macrophage-derived growth factors that have significant effects on the pathology of atherosclerosis and are macrophage-derived proteins.
These factors, and their specific receptors, can be measured in blood samples as follows:
CD8+CD25+, CD4+CD25+, CD8+DRII+, CD4+DRII+, CD4+CD44+, CD8+CD44+, CD4+CD11a+, CD8+CD11a+
CD8+CD38+RO+, CD8+CD28-RA+, CD4+CD49d, CD8+CD49d, CD8+CD11highRA+, CD8+CD11lowRA+, CD8+CD11highRO+, CD14+CD36+, CD14+CD80, CD14+CD86+
CD14+TLR2, CD14 TLR4, CD14+TLR9