Neointimal macrophages colocalize with extracellular matrix gene expression in human atherosclerotic pulmonary arteries.

Abstract

Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal extracellular matrix gene expression, suggesting regulation by local factors. Though the factors responsible for inducing matrix gene expression in atherosclerotic lesions are largely unknown, several observations suggest macrophages may be a focal source of those factors.Immunohistochemistry confirmed the presence of macrophages in the neointima of atherosclerotic elastic pulmonary arteries from patients with unexplained pulmonary hypertension. Areas of neointima containing dense clusters of macrophages were separated by sparsely populated areas. Foamy macrophages resided more deeply within the neointima than nonfoamy macrophages, which were found more often subjacent to the endothelium or within the lumenal one-third of the neointima. Combined immunohistochemistry-in situ hybridization indicated neointimal fibronectin and type I procollagen gene expression was intimately associated only with nonfoamy neointimal macrophages.These observations suggest that: (a) nonfoamy neointimal macrophages participate in the local regulation of extracellular matrix gene expression in atherosclerotic pulmonary arteries; (b) foamy macrophages, which are not associated with matrix gene expression, have undergone modulation of their secretory phenotype. (J. Clin. Invest. 1993. 91:588-594.)

The role of vascular injury and hemodynamics in rat pulmonary artery remodeling.

“…For example, tropoelastin and type I procollagen are expressed by smooth muscle cells within a thick, fibrous neointima composed of smooth muscle-like cells, macrophages and extracellular matrix, similar to the atherosclerotic lesions found in systemic arteries (1)(2)(3)(4). In contrast to systemic arteries, however, neointimal or atherosclerotic changes are rarely observed in normotensive elastic pulmonary arteries, even in the elderly (1) or in the presence of risk factors for systemic vascular atherosclerosis such as diabetes, tobacco smoke, or hypercholesterolemia (2).…”

“…Immunohistochemistry was performed with antibodies to ␣ -smooth muscle actin (Sigma Chemical Co.), macrophages (HAM-56, DAKO), and angiotensin-converting enzyme as previously described (4,26,27).…”

Molecular pathogenesis of pulmonary arterial hypertension

“…Immunohistochemical studies have revealed increased expression of TGF-β, matrix proteins (such as collagen, elastin, fibronectin, tenascin-C, and glycosaminoglycans) (17), macrophages, and T cells (18) as well as inflammatory mediators such as S100A4 (also known as metastasin 1 [Mts1]) (19) and fractalkine (20).…”

Tumor Necrosis Factor-α Induces Fibronectin Synthesis in Coronary Artery Smooth Muscle Cells by a Nitric Oxide–Dependent Posttranscriptional Mechanism

“…30 Expression of NO is elevated in atherosclerotic lesions [31][32][33] as well as in the coronary arteries of human 19 and animal model 20,34 cardiac allografts. Although iNOS was originally identified in cytokine-activated macrophages, several reports have demonstrated that vascular SMCs in culture also produce iNOS [35][36][37][38][39][40] in response to TNF-␣ and IL-1␤. [35][36][37] NOdependent TNF-␣ induction of fibronectin expression was demonstrated in a human umbilical vein endothelial cell line.…”