Cellular Interactions, Growth Factors, and Smooth Muscle Proliferation in Atherogenesis<sup>a</sup>

Ross, Russell; Masuda, Junichi; Raines, EW

doi:10.1111/j.1749-6632.1990.tb42282.x

Cited by 69 publications

(29 citation statements)

References 28 publications

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“…PDGF is composed of two closely related but nonidentical protein subunits, PDGF A-chain and Bchain, which form three possible dimeric configurations; AA, BB, and AB. All three forms of PDGF are mitogenic by binding to specific high-affinity cell surface receptors on mesenchymal cells such as VSMCs, fibroblasts, astrocytes, and osteoblasts (5). PDGF receptors consist of combinations of two different subunits, a-and ,/-receptors, which dimerize to form three distinct receptors; aa, a/3, and /,3.…”

Section: Introductionmentioning

confidence: 99%

“…PDGF is an 28-35 kD peptide which is present in platelets and is secreted from VSMCs, endothelial cells, macrophages, and fibroblasts (5,11). PDGF is composed of two closely related but nonidentical protein subunits, PDGF A-chain and Bchain, which form three possible dimeric configurations; AA, BB, and AB.…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that numerous cellular growth regulatory molecules, in particular PDGF, are responsible for the migration, proliferation, and formation of connective tissue by VSMCs in vitro (5,6). Recent studies (7)(8)(9)(10) showed that antisense PDGF A-chain oligonucleotides and antibodies to PDGF A-chain inhibited growth of cultured VSMCs by potent growth factors, IL-1, IL-6, angiotensin II (A II), and TGF-,/, indicating that the proliferation-inducing activities of these factors are mediated by autocrine secretion of a dimer of PDGF A-chain (PDGF-AA) in cultured VSMCs.…”

Section: Introductionmentioning

confidence: 99%

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Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

Negoro

Kanayama²,

Haraguchi³

et al. 1995

J. Clin. Invest.

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To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Spl and AP-2 in VSMCs of SHRs were twofold more abundant than in those of WistarKyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Spl, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF Achain mRNA and Spl in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF Achain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Spl in these cells. (J. Clin. Invest. 1995Invest. . 95:1140Invest. -1150

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

Negoro

Kanayama²,

Haraguchi³

et al. 1995

J. Clin. Invest.

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“…The finding that 15-lipoxygenase is expressed in macrophages of human atherosclerotic lesions but not in the precursor cell, the monocyte, nor in related cells such as alveolar macrophages (9, 10) prompted us to search for relevant molecules that may account for the disease-specific induction of the enzyme. Because cytokines have been implicated in the cellular response seen in atherosclerosis (11,12), we examined the effect on 15-lipoxygenase expression of different cytokines produced by cells present in atherosclerotic lesions.…”

mentioning

confidence: 99%

Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase.

Conrad

Kühn²,

Mulkins³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

348

244

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Arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase, EC 1.13.11.33) is a lipidperoxidating enzyme that is implicated in oxidizing low density lipoprotein to its atherogenic form. Monocyte/macrophage 15-lipoxygenase is present in human atherosclerotic lesions. To pursue a basis for induction of the enzyme, which is not present in blood monocytes, the ability of relevant cytokines to regulate its expression was investigated. Interleukin 4 (IL4), among 16 factors tested, specifically induced 15-lipoxygenase mRNA and protein in cultured human monocytes. Interferon y and hydrocortisone inhibited this induction. High-performance liquid chromatography analysis of lipid extracts from IL-4-treated monocytes detected 15-lipoxygenase products esterified to the cellular membrane lipids, indicating enzymatic action on endogenous substrates. Stimulation of IL-4-treated monocytes with calcium ionophore or opsonized zymosan A enhanced the formation of 15-lipoxygenase products. These data identify 1L14 and interferon y as physiological regulators of lipoxygenase expression and suggest an important link between 15-lipoxygenase function and the immune/inflammatory response in atherosclerosis as well as other diseases.

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“…The induction of xanthomas (infiltrates of foam cells) in the dermis of hypercholesterolaemic rabbits correlates with serum cholesterol levels [18]. The foam cells can express HLA-DR [19] and arc thought to play a major role in atherogenesis via their interaction with T lymphocytes which are also present in the lesions [20].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

Hughes¹,

Townsend²,

Haslam³

1992

Clinical and Experimental Immunology

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SUMMARYExtrinsic allergic alveolitis (EAA) (synonym: hypcrsensilivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocylic infiltrates in the pulmonary interstitial tissues. We have previously reported thai the numbers of lymphocytes in bronchoalveoiar iavage (BAL) samples in this disease correlate wilh leveis ofcholesierol and neutral lipid-ladcn 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which areknovtn lobe essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesteroi is capable of enhancing the antigenpresenting function of mononuciear phagocytes by moduiating the expression of HLA-D region products. Ineubation of purified monocytes from heaithy volunteers with cholesterol in serum-free medium induced a significant increase in bolh ihe percentages of monocyles expressing HLA-DQ (P< 002) and in Ihe intensity of expression of the three HLA-D sub-region products, HLA-DQ,-DP and -DR {P<0Q2. <001, <005, respeetiveiy). The choieslerol pre-incubated monocytes also exhibited enhanced antigen-presenting function (/'<005), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augmeni aniigen presentation by modulating the expression of HLA-D region products on anligen-preseniing cells. Apart from EAA. this observation may also have relevance lo inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.

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Cellular Interactions, Growth Factors, and Smooth Muscle Proliferation in Atherogenesis^a

Cited by 69 publications

References 28 publications

Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase.

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

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Cellular Interactions, Growth Factors, and Smooth Muscle Proliferation in Atherogenesisa

Cited by 69 publications

References 28 publications

Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase.

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

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Cellular Interactions, Growth Factors, and Smooth Muscle Proliferation in Atherogenesis^a