Nerve growth factor levels and mast cell distribution in human coronary atherosclerosis

Chaldakov, George N.; Stankulov, Ivan S.; Fiore, M.; Ghenev, Peter; Aloe, Luigi

doi:10.1016/s0021-9150(01)00488-9

Cited by 56 publications

(51 citation statements)

References 46 publications

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“…This suggests that the metabolic response, or metabolic adaptations, in the morbidly obese differ considerably from those of the general obese population. The relationship which we observed between NTs and the metabolic derangements associated with obesity or MetSyn differs from the results reported by Chaldakov et al, who reported lower levels of NGF in the vascular wall of human coronary arteries of atherosclerotic patients, as well as in the blood of patients with the MetSyn (10,(26)(27)(28). However, we find significant differences in plasma NGF levels in relation to hyperglycemia or medication use, abdominal fat distribution, and MetSyn.…”

Section: Discussioncontrasting

confidence: 95%

“…Chaldakov and coworkers have hypothesized that a reduction in NT production could be implicated in the pathogenesis of obesity and related comorbidities, and reported that hyponeurotrophinemia was present in a group of patients with the MetSyn or cardiovascular disease and not in healthy subjects (10,(26)(27)(28). However, such a proposal is not in agreement with the relationship described between NTs and other inflammatory diseases (20,21).…”

Section: Discussionmentioning

confidence: 97%

“…Such a link is further supported by the inhibitory effect of dexamethasone and a peroxisome proliferator-activated receptor g agonist on NGF expression and secretion by adipocytes, each having an anti-inflammatory action (12). Interestingly, studies on a small group of patients with cardiovascular disease or the MetSyn have reported a systemic NT deficit in the case of NGF and BDNF (26)(27)(28).…”

Section: Introductionmentioning

confidence: 97%

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Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

et al. 2007

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Objective: Neurotrophins (NTs) could be involved in the development and progression of inflammatory and immune diseases. Because obesity and the metabolic syndrome (MetSyn) are related to a lowgrade systemic inflammation, plasma NT levels (neurotrophinemia) could play an important role in the ethiopathogenic mechanisms underlying these metabolic derangements. This is the first study evaluating the plasma NT levels in a group of women with obesity and MetSyn, and also the adipose tissue nerve growth factor (NGF) expression in a small group of them. Methods: Included were 146 adult women with different degrees of adiposity, with or without MetSyn. Plasma NT levels were measured. NGF expression was analyzed in s.c. adipose tissue of a subgroup of morbidly obese and normal-weight females. Results: NGF plasma levels were 1.4-fold higher in overweight and obese subjects. Plasma NGF was, however, lower in a group of morbidly obese subjects than in overweight or obesity, but it remained elevated relative to the normal-weight group. Plasma NGF was significantly correlated with body mass index (BMI), percentage body fat, and waist circumference in non-morbidly obese subjects. NGF was positively related to inflammatory markers. NT3 and brain-derived neurotrophin factor seem to be more related to lipid profile than to BMI, adipose tissue distribution, or peripheral inflammatory markers. Subjects with type 2 diabetes, abdominal fat distribution, or the MetSyn showed significantly higher levels of NGF. The MetSyn was the only independent predictor of the variability observed in the NGF plasma values. Conclusion: NGF is upregulated in obesity, type 2 diabetes, and the MetSyn. Whether this NT may contribute to inflammation and the metabolic derangements associated with body weight gain remains to be elucidated.

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Section: Discussioncontrasting

confidence: 95%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

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Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

et al. 2007

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“…In such coronary arteries the numbers of MCs and of NGF receptors were increased, whereas the levels of NGF were decreased. 27 We found a significant correlation between numbers of bFGF-positive MCs and microvessels both in adventitia and in the intima. Moreover, in the neovascularized lesions, the intimal areas with the highest numbers of microvessels contained the highest numbers of MCs.…”

Section: Lappalainen Et Al Bfgf In Mast Cells In Human Coronary Arteriesmentioning

confidence: 61%

Mast Cells in Neovascularized Human Coronary Plaques Store and Secrete Basic Fibroblast Growth Factor, a Potent Angiogenic Mediator

Lappalainen

Laine

Pentikäinen

et al. 2004

ATVB

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Objective-Intraplaque neovascularization and hemorrhage may facilitate plaque progression. We studied expression of basic fibroblast growth factor (bFGF), a potent angiogenic mediator, by mast cells (MCs) in human coronary plaques with increasing degrees of atherosclerosis. Methods and Results-Normal and atherosclerotic coronary segments were collected from 30 autopsied subjects.Immunohistochemical methods were used to detect MCs, bFGF, and microvessels. Both adventitial and intimal MCs showed intracytoplasmic granular staining for bFGF, and bFGF-positive extracellular granules were observed close to the MCs. Increased numbers of bFGF-positive MCs were detected in neovascularized areas of plaques, and there was a positive correlation between numbers of bFGF-positive MCs and microvessels in both the intima and adventitia. In plaques, the highly neovascularized areas contained increased numbers of bFGF-positive MCs compared with the adjacent nonvascularized areas, where only few MCs were present. Importantly, the proportion of intimal MCs expressing bFGF increased with increasing severity of atherosclerosis. Conclusions-The present work reveals a novel source of bFGF in human coronary arteries, the intimal and adventitialMCs. See coverExpression of bFGF has been found in human atherosclerotic plaques (eg, in femoral, carotid, and coronary arteries), with the cell types responsible for bFGF expression being ECs, SMCs, and macrophages. [2][3][4] Increased expression of bFGF is found in coronary atherectomy specimens from patients with clinically unstable angina, compared with specimens from patients with stable coronary disease. 2 Moreover, bFGF is 1 of the angiogenic growth factors currently studied to induce therapeutic angiogenesis in ischemic human tissues. 5,6 The mast cell (MC) is a type of inflammatory cell implicated in angiogenesis. 7 In human coronary atheromas, MCs appear near intimal neovessels, 8 and in the adventitia, MCs are often located close to the vasa vasorum. 9 These localizations of coronary MCs suggest that in coronary atheromas they may contribute to neoangiogenesis. Increased numbers of bFGF-positive MCs have been found in tissues characterized by neovascularization, fibrosis, and inflammation, such as human fibrotic lung and cutaneous hemangiomas. 10,11 In MCs, bFGF is located predominantly in the heparincontaining granules. 12 The emerging concept of intraplaque neovascularization and hemorrhage as factors contributing to plaque progression 13,14 prompted us to search for bFGF in MCs in human coronary arteries showing various degrees of atherosclerosis. Methods Autopsy MaterialThe autopsy series comprised 30 cases (24 men and 6 women) aged 34 to 78 years. The proximal left coronary artery was removed, cut into successive segments 5 mm long, fixed in neutral buffered formalin, and embedded in paraffin. Sections (2 to 4 m) were stained with hematoxylin-eosin and elastica-van Gieson and evalu- ImmunohistochemistryThe tissue sections were deparaffinized and rehydrated, and endogenous peroxid...

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“…Basic animal and clinical human studies have implicated inflammatory as well as fibroproliferative mechanisms in atherosclerosis [2]. Primarily initiated by endothelial dysfunction, this disease develops as a result of a complex interplay between various growth factors, cytokines, vascular smooth muscle cells and immune cells [3]. Nerve Growth Factor (NGF) is a powerful endogenous mediator that plays a prominent role in differentiation, survival and regeneration of sympathetic and sensory peripheral nerve cells [4].…”

Section: Introductionmentioning

confidence: 99%

Reduced NGF-Serum Concentrations in Coronary Artery Disease Patients Increase after Coronary Artery Bypass Grafting

Köhler¹

2012

J Clin Exp Cardiolog

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Background: Coronary Artery Disease (CAD) is the leading cause of death worldwide, but neurological deficits are the most devastating complications of its treatment, Coronary Artery Bypass Surgery (CABG). As Nerve Growth Factor (NGF) has been implicated in the modulation of inflammatory and fibroproliferative mechanisms leading to atherosclerosis as well as in neuroprotection and survival of neurons, the time course of NGF serum concentrations during CABG has been studied. Methods:Twenty-six male patients were scheduled for coronary artery bypass grafting and NGF levels have been measured 1 hour before the operation started and 2, 5 and 120 hours postoperatively. Pre-operation values of NGFs were compared to healthy controls. Results:We found significantly lower NGF serum concentrations in coronary artery disease patients (n=26, age: 68.8 ± 5.5 years, mean NGF: 13.04 ± 32.1 pg/ml) as compared to age-matched healthy controls (n=20, age: 64.35 ± 4.15, mean NGF: 29.54 ± 24.23 pg/ml). A significant increase of NGF was found 120 hours after operation (Z=3.26, p=0.001).Conclusion: NGF seems to be decreased in coronary artery disease and is increased by operative coronary revascularization procedures. Changes occurring during cardiac surgery may indicate beneficial regenerative processes but may also implicate neuronal alterations induced by operative procedures.

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Nerve growth factor levels and mast cell distribution in human coronary atherosclerosis

Cited by 56 publications

References 46 publications

Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

Mast Cells in Neovascularized Human Coronary Plaques Store and Secrete Basic Fibroblast Growth Factor, a Potent Angiogenic Mediator

Reduced NGF-Serum Concentrations in Coronary Artery Disease Patients Increase after Coronary Artery Bypass Grafting

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