DOES PLATELET-DERIVED GROWTH FACTOR-A CHAIN STIMULATE PROLIFERATION OF ARTERIAL MESENCHYMAL CELLS IN HUMAN ATHEROSCLEROTIC PLAQUES

Previous studies have indicated the focal presence of growth factors a nd focal low levels of cell proliferation in human atherosclerotic pla ques. Using human carotid plaques and an antibody to platelet-derived growth factor (PDGF)-A chain, we have begun to assess growth factor si gnificance by spatially correlating growth factor gene expression with actual cell proliferation. Since PDGF is a mitogen for smooth muscle and related cells and since inflammatory cells (eg, macrophages) can a lso proliferate in these lesions, it was important to exclude inflamma tory cell proliferation from this consideration. Therefore, we have us ed a triple immunolabeling approach, combining the above anti-PDGF-A c hain antibody with an inflammatory cell cocktail (CD68+CD45 for monocy te/macrophages and lymphocytes) and adding an anti-proliferating cell nuclear antigen (PCNA) antibody to mark proliferating cells. In the ca rotid atherosclerotic plaques, PDGF immunostaining was distributed foc ally, preferentially in the fibrous cap and vascularized regions, and was present in two distinct patterns: cytoplasmic and diffuse extracel lular staining. When we considered colocalization within the same cell s, cytoplasmic PDGF-A staining did not appear to colocalize with infla mmatory markers. PCNA nuclear staining combined with PDGF cytoplasmic staining of the same cell was detected extremely rarely. Considering c olocalization within the same microscopic fields, PDGF-A staining was detected more frequently than noninflammatory PCNA positivity. Quantit ative logistic regression analysis demonstrated that localization in v ascularized regions and (independently) the presence of PDGF-A are goo d predictors of noninflammatory cell proliferation, within the same mi croscopic fields. Therefore, PDGF-A and other factors especially assoc iated with vascularized regions may be involved in the regulation of m esenchymal cell proliferation in human atherosclerotic plaques.