Growth Factors Released Into the Coronary Circulation After Vascular Injury Promote Proliferation of Human Vascular Smooth Muscle Cells in Culture

Caplice, Noel M.; Aroney, Constantine N.; Bett, J. H. N.; Cameron, James N.; Campbell, Julie H.; Hoffmann, Nancy; McEniery, Paul T.; West, Malcolm

doi:10.1016/s0735-1097(97)00076-4

Cited by 33 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of cell proliferation, together with other well-documented effects of ®sh oil decreasing platelet aggregation (Mori et al, 1997), blood pressure (Morris et al, 1993) and modulating blood lipids (Connor et al, 1993), may contribute to the reported reduction in restenosis. Given that growth factor activity is higher following angioplasty (Caplice et al, 1997), it is possible that ®sh oil exerts lowering effects only in pathological states where growth factor levels are elevated. This may explain our observation of no signi®cant effect of ®sh oil on serum growth factor activity in apparently healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

“…Platelet-derived growth factor (PDGF) expression is elevated in human atherosclerotic plaques compared with normal arteries, and increased plasma concentrations of PDGF have been reported in patients with diagnosed vascular disease (Wallace et al, 1998;Nilsson et al, 1986). Total mitogenic activity of serum for smooth muscle cells is elevated in individuals at risk of developing the clinical symptoms of IHD (Koschinsky et al, 1987) and also in acute studies of patients undergoing coronary angioplasty (Caplice et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans

et al. 2000

View full text Add to dashboard Cite

Objective: To examine the effect of low-dose ®sh oil supplementation on speci®c growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. Design: Randomized placebo-controlled double-blind intervention study. Setting: Free-living population. Subjects: Sixty-three healthy volunteers, 37 males and 26 females. Interventions: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 gaday of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. Results: Consumption of ®sh oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFb) concentration. Furthermore, ®sh oil supplementation did not alter the total growth factor activity of serum. Conclusions: Results indicate that low-dose ®sh oil supplementation, equivalent to about two portions of fatty ®sh per week and providing less than 1 g n-3 PUFAaday, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. Sponsorship: European Union shared cost project (FAIR-CT-95-0085).

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Several serum-derived growth factors are known to be upregulated locally and released in atherosclerosis [22][23][24] and after coronary angioplasty in human subjects. 25 It is possible that growth factors within the vessel wall might locally regulate TFPI synthesis and secretion. Future studies will need to assess regulation of TFPI in vascular disease states where TF/factor VII activation plays a major role in thrombosis formation.…”

Section: Discussionmentioning

confidence: 99%

Expression of Tissue Factor Pathway Inhibitor in Vascular Smooth Muscle Cells and Its Regulation by Growth Factors

Caplice

Mueske

Kleppe

et al. 1998

Circulation Research

View full text Add to dashboard Cite

Abstract-Tissue factor pathway inhibitor (TFPI) in vivo is thought to be synthesized mainly by endothelial cells. To date, no significant regulator of TFPI synthesis has been described. Vascular smooth muscle cells (VSMC) express tissue factor in vitro and in vivo, which may contribute to vascular thrombosis. We hypothesized that VSMC might also express TFPI. To determine this, we examined growth-arrested coronary VSMC in culture and found that VSMC secreted an amount of TFPI similar to that seen in endothelial cells. Immunohistochemistry of normal human coronary arteries showed TFPI staining throughout the media and intima of the vessel with localization to VSMC and endothelial cells. To determine regulation of TFPI expression in VSMC, we examined the effects of serum stimulation on TFPI secretion and found that FBS induced a 5-fold increase in TFPI antigen and activity levels in conditioned medium at 48 hours (PϽ0.001) when compared with serum-free conditions. A similar stimulatory effect was seen with 10% pooled human serum. Moreover, epidermal growth factor and platelet-derived growth factor-B increased TFPI secretion by 4-to 5-fold and 2-to 3-fold, respectively (PϽ0.05), and these growth factors accounted for Ϸ50% of the TFPI secretion effects of human serum. The serum effect was associated with a 3-fold increase in TFPI mRNA 24 hours after release from growth arrest and a 50% decrease in TFPI secretion after treatment with actinomycin D. Taken together, this study suggests that there is significant TFPI expression in VSMC in culture and in VSMC within the intima and media of the normal coronary artery wall. We present the first evidence for TFPI regulation by serum in VSMC and more specifically by its constituent growth factors, epidermal growth factor and platelet-derived growth factor-B. (Circ Res. 1998;83:1264-1270.)Key Words: tissue factor Ⅲ inhibitor Ⅲ smooth muscle Ⅲ regulation A rterial thrombosis is a significant complication of primary atherosclerosis. The complex of tissue factor (TF) and factor VIIa is one of the most potent initiators of in vivo arterial thrombosis, leading to activation of factors IX and X. 1 Several studies have shown that TF is expressed in the adventitia of normal human arteries, 2,3 intima of human atherosclerotic plaque, and neointima of the balloon-injured rat arteries. 4 An important inhibitor of TF-mediated coagulation is tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor with 3 Kunitz-type domains that inactivates factor Xa generation by binding initially via its Kunitz II domain to factor Xa and subsequently by its Kunitz I domain to TF-VIIa catalytic complex. 5 The formation of a quaternary TF-VIIa-TFPI-Xa complex dampens ongoing coagulation and may allow modulation of thrombosis in vivo. TFPI was purified initially from conditioned medium of a hepatoma cell line (HepG2) 6 and since has been described in platelets, microvascular endothelium, and stimulated blood monocytes. 7-10 The endothelium currently is thought to be the principle site of in...

show abstract

“…1 Numerous growth factors and mitogenic autocoids that could accelerate new tissue formation and development of the restenotic lesion have been found at the site of injury. 2,3 Signal transduction by these agents involves the mitogen-activated protein kinase (MAPK) pathway, and p21 rasdependent activation of p42/p44 MAPK has been demonstrated in vivo in a porcine model of balloon injury early after angioplasty. 4 Moreover, the local delivery of H-ras dominant negative mutant (N17 and L61, S186) plasmid constructs 5 and adenovirus-mediated transfer of dominant negative H-ras 6 have both been shown to significantly reduce neointima formation in the rat carotid artery.…”

mentioning

confidence: 99%

Short-Term Local Delivery of an Inhibitor of Ras Farnesyltransferase Prevents Neointima Formation In Vivo After Porcine Coronary Balloon Angioplasty

et al. 2001

View full text Add to dashboard Cite

Background-Mitogenic stimuli present at the site of coronary arterial balloon injury contribute to the progression and development of a restenotic lesion, many signaling through a common pathway involving the small G protein p21 ras .Our aim was to demonstrate in biochemical studies that farnesyl protein transferase inhibitor III (FPTIII) is an inhibitor of p21 ras processing and that when it is given locally in vivo at the site of coronary balloon injury in a porcine model, it can inhibit neointima formation. Methods and Results-FPTIII (1 to 25 mol/L) concentration-dependently reduced p21 ras levels in porcine coronary artery smooth muscle cell membranes. FPTIII also prevented p42/p44 MAPK activation and DNA synthesis in response to platelet-derived growth factor in these cells at a concentration of 25 mol/L. Application of 25 mol/L FPTIII locally for 15 minutes to balloon-injured porcine coronary arteries in vivo prevented neointima formation assessed at 4 weeks, reduced proteoglycan deposition, and inhibited adventitial hypertrophy. Coronary arteries from FPTIII-treated pigs had no deterioration in contraction or in endothelium-dependent relaxation. Conclusions-The study demonstrates in the pig that short-term local delivery of inhibitors of p21 ras -dependent mitogenic signal transduction prevents restenosis after balloon angioplasty.

show abstract

Growth Factors Released Into the Coronary Circulation After Vascular Injury Promote Proliferation of Human Vascular Smooth Muscle Cells in Culture

Abstract: The change in plasma PDGF level is consistent with first-phase release of PDGF after vascular injury. The increase in mitogenicity of serum suggests that PDGF and bFGF are biologically active.

Cited by 33 publications

References 20 publications

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans

Expression of Tissue Factor Pathway Inhibitor in Vascular Smooth Muscle Cells and Its Regulation by Growth Factors

Short-Term Local Delivery of an Inhibitor of Ras Farnesyltransferase Prevents Neointima Formation In Vivo After Porcine Coronary Balloon Angioplasty

Contact Info

Product

Resources

About