A pro-fibrotic role for interleukin-4 in cardiac pressure overload.

Aims: The mechanisms underlying cardiac fibrosis in hypertension are yet to be defined, although inflammatory cells, fibroblasts, and cytokines have been implicated. Here, we investigated the role of interleukin-4 (IL-4) in cardiac fibrosis, which is elevated in the hypertensive heart. IL-4 has been shown to be pro-fibrotic in the liver and the lung, but its role in cardiac fibrosis has not been investigated.

Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions: role of activated macrophages and cytokines.

Objective: Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. High-mobility group box 1 (HMGB1) is a DNA-binding protein, which on release from cells exhibits potent inflammatory actions. We examined its expression in atherosclerotic lesions and regulation by cytokines.

Proliferation of neointimal smooth muscle cells after arterial injury. Dependence on interactions between fibroblast growth factor receptor-2 and fibroblast growth factor-9.

The growth factor signaling mechanisms responsible for neointimal smooth muscle cell (SMC) proliferation and accumulation, a characteristic feature of many vascular pathologies that can lead to restenosis after angioplasty, remain to be identified. Here, we examined the contribution of fibroblast growth factor receptors (FGFRs) 2 and 3 as well as novel fibroblast growth factors (FGFs) to such proliferation. Balloon catheter injury to the rat carotid artery stimulated the expression of two distinctly spliced FGFR-2 isoforms, differing only by the presence or absence of the acidic box, and two distinctly spliced FGFR-3 isoforms containing the acidic box and differing only by the presence of either the IIIb or IIIc exon.

Distinct patterns of transforming growth factor-beta isoform and receptor expression in human atherosclerotic lesions. Colocalization implicates TGF-beta in fibrofatty lesion development.

Background: Some animal studies suggest that transforming growth factor-beta (TGF-beta) protects vessels from atherosclerosis by preventing intima formation, but others indicate a role in vessel proteoglycan accumulation and lipoprotein retention. To distinguish between these possibilities in humans, immunohistochemical studies were performed examining the coexpression of TGF-beta isoforms and the TGF-beta receptors ALK-5 and TbetaR-II in aorta during the various stages of atherosclerotic lesion development.

Methods And Results: The spatial relationships between TGF-beta1, TGF-beta3, ALK-5, and TbetaR-II expression were compared in aortic segments from 21 subjects.