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Antoine Lafont

Publications and source records attributed to Antoine Lafont.

At least 19 recordsLinked to original sources
PubMed2006

PLA stereocopolymers as sources of bioresorbable stents: preliminary investigation in rabbit.

The aim of the present work was to evaluate whether the degradation of PLA-based bioresorbable stents can be modulated via the configuration of repeating units as it is the case in other applications like osteosynthesis. The first obstacle was finding a stent design that could allow implantation in the aorta of a rabbit taken as a model of a human coronary artery. In the absence of guidelines other than those tentatively proposed in patents, several simple designs were considered that allowed us to evaluate the fate of the stents made of poly(lactic acid) stereocopolymers with L/(L + D) ratio of 0.92 (PLA92) and 0.50 (PLA50) up to 6 months post in vivo implantation. Our findings show the feasibility of bioresorbable stenting using PLA stereocopolymers and that PLA50 degraded faster than PLA92. Therefore, using stereocopolymers appears as a means to vary the degradation rate and adapt it to the artery remodelling process that is very much dependent on the release of the stenting stress protection.

Animals↗
PubMed2006

Phenotypic study of human gingival fibroblasts labeled with superparamagnetic anionic nanoparticles.

BACKGROUND: A specific labeler of the human gingival fibroblast (HGF) does not exist. Anionic maghemite nanoparticles allow labeling of a wide cell variety and their recognition in cellular, organotypical, and animal models. METHODS: We studied internalization effects of nanoparticles on an HGF phenotype in vitro, evaluating transcription and secretion of connective tissue remodeling molecules, i.e., matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines controlling their activation/inhibition, i.e., transforming growth factor-beta (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), and interleukins 1beta and 4 (IL-1beta and IL-4). After proliferation kinetics, cellular uptake was studied by Perls coloration and magnetophoresis on labeled culture. Dot blotting, Western blotting, and zymography were used to detect MMP-1, -2, and -3 and TIMP-1 and -2 secretions in culture supernatants, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the mRNA expression of these molecules. Enzyme-linked immunosorbent assay (ELISA) tests were used to determine TGF-beta1, TNF-alpha, IL-1beta, and IL-4 levels. RESULTS: Our data indicated high (15.3+/-5.8 pg/cell) but heterogeneous distribution of nanoparticles in HGF. Twenty-four hours after labeling, MMP-1, -2, and -3 and TIMP-2 secretion increased (P<0.001) with RT-PCR confirmation at 12 hours, whereas TIMP-1 did not. IL-1beta increased at day 1 (D1) (P<0.001) and IL-4 at D3 (P<0.01), but not TGF-beta1 or TNF-alpha. CONCLUSIONS: After labeling with these maghemite nanoparticles, HGF increased secretion of IL-1beta at D1, probably inducing the increase of MMP-1, -2, and -3 and TIMP-2. The increase of IL-4 secretion began with the decreased synthesis of MMPs and TIMPs at D3. Despite this transitory inflammatory reaction at 3 days following internalization, maghemite nanoparticles did not affect HGF phenotype, thereby authorizing their use as labelers.

Adult↗
PubMed2005

Reduced immunoregulatory CD31+ T cells in patients with atherosclerotic abdominal aortic aneurysm.

BACKGROUND: Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal aortic aneurysms (AAA). In particular, infiltrating macrophages and CD8+ T lymphocytes participate in the destruction of the aortic wall extracellular matrix and smooth muscle cells. We surmise that these pathological events are controlled by circulating regulatory lymphocytes. METHODS AND RESULTS: Circulating CD4+/CD31+ cells were reduced in AAA patients (n=80, 8.9+/-0.6%) as compared with controls (n=69, 13.7+/-0.8%; P<0.001) and inversely proportional to AAA size. Exclusion of the aneurysm by an endoprothesis did not affect CD31+ T cell values. Reduction of blood CD4+/CD31+ cells was not attributable to their enrichment in AAA tissue. In contrast, CD8+/CD31+ cells were slightly reduced in the blood while increased in the aneurysmal tissue (29.2+/-0.5 versus 20.2+/-4.7% in blood, n=6; P<0.05). Remarkably, high percentages of CD4+/CD31+ cells were able to regulate proliferation and cytokine production of CD8+ lymphocytes, as well as CD8+ cell-mediated cytotoxicity of aortic smooth muscle cells (P<0.01). Finally, CD4+/CD31+ cells reduced the production and activity of metalloproteinase-9 by lipopolysaccharide-stimulated macrophages. CONCLUSIONS: Circulating CD4+/CD31+ T cells regulate macrophage and CD8+ T cell activation and effector function in the arterial wall. Their reduction might promote the development of AAA.

Aged↗
PubMed2005

Isolation of "side population" progenitor cells from healthy arteries of adult mice.

OBJECTIVE: Circulating progenitors and stem cells have been reported to contribute to angiogenesis and arterial repair after injury. In the present study, we investigated whether the arterial wall could host permanently residing progenitor cells under physiological context. METHODS AND RESULTS: Using the Hoechst-based flow cytometry method, we identified and isolated progenitor cells termed side population (SP) cells at a prevalence of 6.0+/-0.8% in the tunica media of adult mice aortas. Arterial SP cells expressed the ATP-binding cassette transporter subfamily G member 2, frequently present on SP cell surface, and displayed a Sca-1+ c-kit(-/low) Lin- CD34(-/low) profile. They did not form myeloid or lymphoid hematopoietic colonies after plating in methylcellulose-based medium. Importantly, cultured SP cells were able to acquire the phenotype of endothelial cells (CD31, VE-cadherin, and von Willebrand factor expression) or of smooth muscle cells (alpha-smooth muscle actin, calponin, and smooth muscle myosin heavy chain expression), in presence of either vascular endothelial growth factor or transforming growth factor (TGF)-beta1/PDGF-BB, respectively. Moreover, they generated vascular-like branching structures, composed of both VE-cadherin+ cells and alpha-smooth muscle actin+ cells on Matrigel. CONCLUSIONS: In this study, we provide the first evidence to our knowledge that in the adult mice, the normal arterial wall harbors SP cells with vascular progenitor properties.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2005

Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice.

Atherosclerosis results from accumulation of macrophages and extracellular matrix in the arterial wall. Decorin, a small matrix proteoglycan, is able to regulate cell proliferation, migration and growth factors' activity. We investigated the effect of decorin overexpression on atherosclerosis progression in apolipoprotein E-deficient (ApoE(-/-)) mice. Female ApoE(-/-) mice, 10 weeks old (early treatment, n = 20) and 20 weeks old (delayed treatment, n = 20) were administered intravenously with either an adenovirus (2.5 x 10(9) plaque-forming units/mouse) containing human decorin gene (Ad-Dcn) or beta-galactosidase (LacZ), or PBS. Transgenic decorin was mainly expressed in the liver, and was secreted in the plasma up to 4 weeks. Six weeks after treatment, no significant difference in aortic root lesion size was observed between LacZ- and PBS-control groups. In contrast, Ad-Dcn-treated mice showed significantly reduced atherosclerotic lesions as compared to controls in both early and delayed treatment groups (2.9 +/- 1.1% versus 5.5 +/- 0.4%; p = 0.004 and 13.4 +/- 1.3% versus 19.9 +/- 1.41%; p = 0.009, respectively). In parallel, macrophage, gelatinase activity and collagen plaque content were also reduced. Interestingly, plasma triglycerides were reduced and decorin formed complexes with transforming growth factor-beta1 (TGF-beta1) that resulted in reduced circulating free-TGF-beta1. In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE(-/-) mice resulting in slowing down of disease progression.

Amyloid↗
PubMed2005

Collagen and elastin cross-linking: a mechanism of constrictive remodeling after arterial injury.

Constrictive remodeling after arterial injury is related to collagen accumulation. Cross-linking has been shown to induce a scar process in cutaneous wound healing and is increased after arterial injury. We therefore evaluated the effect of cross-linking inhibition on qualitative and quantitative changes in collagen, elastin, and arterial remodeling after balloon injury in the atherosclerotic rabbit model. Atherosclerotic-like lesions were induced in femoral arteries of 28 New Zealand White rabbits by a combination of air desiccation and a high-cholesterol diet. After 1 mo, balloon angioplasty was performed in both femoral arteries. Fourteen rabbits were fed beta-aminopropionitrile (beta-APN, 100 mg/kg) and compared with 14 untreated animals. The remodeling index, i.e., the ratio of external elastic lamina at the lesion site to external elastic lamina at the reference site, was determined 4 wk after angioplasty for both groups. Pyridinoline was significantly decreased in arteries from beta-APN-treated animals compared with controls, confirming inhibition of collagen cross-linking: 0.30 (SD 0.03) and 0.52 (SD 0.02) mmol/mol hydroxyproline, respectively (P = 0.002). Scanning and transmission electron microscopy showed a profound disorganization of collagen fibers in arteries from beta-APN-treated animals. The remodeling index was significantly higher in beta-APN-treated than in control animals [1.1 (SD 0.3) vs. 0.8 (SD 0.3), P = 0.03], indicating favorable remodeling. Restenosis decreased by 33% in beta-APN-treated animals: 32% (SD 16) vs. 48% (SD 24) (P = 0.02). Neointimal collagen density was significantly lower in beta-APN-treated animals than in controls: 23.0% (SD 3.8) vs. 29.4% (SD 4.0) (P = 0.004). These findings suggest that collagen and elastin cross-linking plays a role in the healing process via constrictive remodeling and restenosis after balloon injury in the atherosclerotic rabbit model.

Aminopropionitrile↗
PubMed2005

Reduced immunoregulatory CD31+ T cells in the blood of atherosclerotic mice with plaque thrombosis.

OBJECTIVE: Lymphocyte activation is thought to play a major role in the pathogenesis of atherosclerotic complications such as plaque thrombosis. Circulating CD31+ T cells have been shown to regulate human T cell activation. Aim of this study was to evaluate whether the proportion of circulating immunoregulatory CD31+ T cells is correlated to the occurrence of plaque thrombosis in aged apolipoprotein (apo) E knockout (KO) mice. METHODS AND RESULTS: CD31+ T cell depletion of spleen T cells enhanced proliferation (P<0.05) and interferon-gamma production (P<0.01) while reducing interleukin (IL)-4 (P<0.001) and IL-10 (P=0.001) secretion in response to minimally modified low-density lipoprotein. CD31+ T cells were counted in 65 apoE KO mice (46-week-old) by flow cytometry. Organizing thrombi could be documented in 28 of 195 (14%) lesions and in at least one of the aorta root lesions in 23 of 65 mice (35%). CD31+ T cell count was significantly reduced in mice showing plaque thrombosis (72.3+/-1.5% versus 84.1+/-1.2%; P<0.0001), but such reduction did not follow induced plaque rupture or experimentally controlled thrombosis. CONCLUSIONS: Reduced CD31+ T cells in circulating blood is a hallmark of atherosclerotic plaque thrombosis. Our data suggest that CD31+ T cells may play an important regulatory role in the development of plaque thrombosis.

Animals↗
PubMed2005

Adenovirus-mediated gene transfer of superoxide dismutase and catalase decreases restenosis after balloon angioplasty.

BACKGROUND: Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty. METHODS: O(2)(-) and H(2)O(2 )production was quantified in cultured cells after incubation with either LPS or CuSO(4). Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control. RESULTS: ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 +/- 27 vs. 63 +/- 19%, p = 0.003) and less constrictive remodeling (1.2 +/- 0.3 vs. 0.9 +/- 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 +/- 4 vs. -1 +/- 6%, p < 0.05), lower collagen density (43 +/- 16 vs. 53 +/- 23%, p = 0.03), and lower inflammatory cell infiltration (22 +/- 6 vs. 36 +/- 11%, p = 0.04) than control arteries. CONCLUSIONS: Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.

Adenoviridae↗
PubMed2005

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium.

AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.

Animals↗
PubMed2005

Obstructive sleep apnoea and patent foramen ovale: successful treatment of symptoms by percutaneous foramen ovale closure.

Obstructive sleep apnoea (OSA) is a common sleep disorder often associated with cardiovascular problems. The role of right to left shunt through a patent foramen ovale (PFO) in OSA is still debated. We report the case of a 42-year-old man with OSA, treated by nocturnal continuous airway pressure, who had a PFO and severe dispnoea and desaturation at exercise. Percutaneous closure of PFO leads to immediate and complete resolution of symptoms. Our report shows for the first time that patients with OSA, PFO, and desaturation at exercise should be considered candidates to PFO closure, even in the absence of cerebral events.

Adult↗
PubMed2003

Incomplete resolution of ST-segment elevation is a marker of transient microcirculatory dysfunction after stenting for acute myocardial infarction.

BACKGROUND: Incomplete ST-segment resolution (STR) after successful primary angioplasty for acute myocardial infarction (AMI) is associated with a poor prognosis. We used intracoronary Doppler velocimetry to investigate whether incomplete STR after primary angioplasty is a marker of severe microcirculatory dysfunction. METHODS AND RESULTS: Fifty patients with < or =12-hour AMI underwent successful primary angioplasty and systematic stenting with a Doppler guidewire. Patients with incomplete (<50%) STR 60 minutes after TIMI 3 flow was restored had flow velocity features suggestive of severe microcirculatory dysfunction, including a higher incidence of early systolic retrograde flow (41% versus 9%, P=0.007) and lower coronary flow velocity reserve (CVR, 1.3 versus 1.6, P<0.001). CVR improved immediately after stenting in patients with > or =50% STR but not in patients with <50% STR. There was a significant correlation between STR and poststent CVR. At 3 months, CVR was similar in patients with <50% and > or =50% STR. However, left ventriculography indicated lower global (42% versus 55%, P=0.001) and regional (16% versus 20%, P=0.03) left ventricular ejection fractions and 201Tl rest-redistribution scintigraphy indicated a larger infarct size (34% versus 16% 201Tl defect, P=0.007) in patients with <50% STR. CONCLUSIONS: After successful primary angioplasty with systematic stenting, <50% STR is a marker of severe albeit transient microcirculatory dysfunction in patients with AMI and is associated with more extensive myocardial damage.

Aged↗
PubMed2003

Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation.

We carried out a prospective evaluation of a new vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay in order to detect patients with high-risk coronary subacute stent thrombosis (SAT) despite thienopyridine regimen. Twenty healthy donors (group 1) without any medication were compared to 16 stented patients (group 2) treated by ticlopidin or clopidogrel initiated 2 days before stenting and aspirin (250 mg/day). No difference in platelet reactivity was noted between group 1 and group 2 treated only with aspirin (72.00% +/- 4.17% vs. 69.73% +/- 5.62%, respectively; P = NS). Significant differences were found between patients of group 2 treated with aspirin alone (69.73% +/- 5.62%), after 2.0 days (60.14% +/- 9.60%; P < 0.05), and after 4.8 +/- 1.3 days (48.37% +/- 11.19%; P < 0.05) with thienopyridine-aspirin. Among 1,684 consecutive stented patients, 16 patients who presented an SAT (group 3) were compared with 30 other stented patients free of SAT (group 4). We found a significant difference between group 3 (63.28% +/- 9.56%) and group 4 (39.80% +/- 10.9%; P < 0.0001). VASP phosphorylation analysis may be useful for the detection of coronary SAT.

Aged↗
PubMed2003

Effect of adenovirus-mediated overexpression of decorin on metalloproteinases, tissue inhibitors of metalloproteinases and cytokines secretion by human gingival fibroblasts.

Decorin is a small leucine-rich proteoglycan that plays a role in control of cell proliferation, cell migration, collagen fibrillogenesis and modulation of the activity of TGF-beta. In the present study, we investigated the effects of decorin on the production of metalloproteinases (MMP-1, -2, -3, -9 and -13), tissue inhibitors of metalloproteinases (TIMP-1, -2) and cytokines (TGF-beta, IL-1beta, IL-4 and TNF-alpha). Decorin was overexpressed in cultured human gingival fibroblasts using adenovirus-mediated gene transfer. Decorin infection resulted in decreased protein levels of MMP-1 and MMP-3 whereas MMP-2 and TIMP-2 secretion was increased. MMP-9, MMP-13 and TIMP-1 were not affected by decorin infection. Cytokine measurements by ELISA showed that decorin overexpression reduced TGF-beta and IL-1beta. In contrast, IL-4 and TNF-alpha levels were markedly increased in decorin-infected cells. These results suggest that decorin could modulate the expression of certain metalloproteinases and their inhibitors, as well as the production of cytokines. Altogether, our data suggest that decorin might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation.

Adenoviridae↗
PubMed2002

Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model.

OBJECTIVES: We sought to evaluate whether cellular mass changes (including apoptosis and proliferation) after arterial injury could interact with restenosis and arterial remodeling. BACKGROUND: The mechanisms controlling arterial remodeling after angioplasty remain poorly understood. Apoptosis and cell proliferation have been previously described after balloon angioplasty. However, their importance in the occurrence of arterial remodeling and restenosis is unknown. METHODS: Atherosclerosis was induced in 48 femoral arteries of New Zealand White rabbits by air-desiccation and a high-cholesterol diet. One month later, angioplasty was performed in 40 arteries. Apoptosis, cell proliferation, residual stenosis and arterial remodeling were evaluated at 2 h and 3, 7, 14, 21 and 28 days after angioplasty. RESULTS: Cell proliferation and apoptosis profiles were similar, but the peak in cell proliferation occurred approximately four days earlier than the peak in apoptosis in the neointima and media. Apoptosis density was positively correlated with arterial remodeling in the neointima and media (r = 0.69, p = 0.005 and r = 0.50, p = 0.05, respectively). Moreover, residual stenosis was inversely correlated with apoptosis density in the neointima and media (r = -0.62, p = 0.008 and r = -0.52, p = 0.04, respectively). In contrast, cell proliferation was independent of restenosis and arterial remodeling. CONCLUSIONS: In this model, cell proliferation preceded apoptosis throughout the four weeks after angioplasty. Apoptosis was inversely correlated with restenosis. Interestingly, apoptosis was also related to enlargement remodeling after balloon angioplasty.

Angioplasty, Balloon, Coronary↗